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1,494 results on '"Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1)"'

1. Post-natal development of the ghrelin system and impact of medium-chain fatty acid-enriched formula feeding in Yucatan mini-pigs

Author

M. Louvois, Gaëlle Boudry, Daniel Catheline, Isabelle Le Huërou-Luron, Vincent Rioux, Armelle Cahu, Véronique Romé, S. Blat, 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), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
medicine.medical_specialty, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Gastric Content, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Gene expression, Internal Medicine, medicine, Receptor, Antrum, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, Meal, Nutrition and Dietetics, Chemistry, digestive, oral, and skin physiology, Fatty acid, Metabolism, Endocrinology, Ghrelin, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Introduction The ghrelin-ghrelin receptor system is one of the most important mechanisms regulating food intake, energy balance and metabolism. Despite the growing interest on nutritional programming of eating disorders, post-natal development of the ghrelin system is currently poorly explored. Moreover, to be fully active, ghrelin must be acylated with medium-chain fatty acids (MCFA) via gastric enzymes (ghrelin-O-acetyl transferase (GOAT), convertase 1/3 (PCSK1/3)). Several reports described dietary modulation of this ghrelin acylation. Therefore, our study aimed at describing early post-natal development of the ghrelin system in mini-pigs as a model of human neonates and the impact of formula-feeding with either a standard or a MCFA-enriched formula on this development. Methods 36 sow-fed piglets were sacrificed 1 h after suckling at post-natal day (PND) 0, 2, 5 and 10. In parallel, 18 piglets were fed from birth to PND10 either a standard infant formula (STD-IF) or a dairy lipid -enriched formula to increase MCFA concentration (DL-IF, MCFA 4.7% of total fatty acid vs. 0.1% in STD-IF) and sacrificed 1 h after their last meal. Results Levels of pre-proghrelin (GHRL) and GOAT mRNA in the antrum did not vary with age (P = 0.79), while that of PCSK1/3 dropped by 50% between PND0 and 2 and slightly re-increased thereafter (P 0.05) but increased GOAT mRNA (+ 60%, P = 0.05). Total and acylated ghrelin plasma concentration were not affected by STD-IF feeding (P > 0.05). DL-IF feeding increased antrum MCFA concentration by 354% (P = 0.009) compared to suckling animals but had not impact on GHRL and PCSK1/3 antral mRNA levels (P > 0.05) nor on plasma total or acylated ghrelin levels (P > 0.05). GOAT mRNA level in MCFA-IF-fed piglets remained significantly greater than in suckling animals (+ 55%, P = 0.03). Plasma acylated/total ghrelin ratio and GOAT mRNA level correlated positively with MCFA concentration in gastric content (r = 0.565, P = 0.004 and r = 0.505, P = 0.01, respectively) while GHRL and PCSK1/3 mRNA levels correlated positively with MCFA concentration in gastric tissue (r = 0.567, P = 0.004 and r = 0.459, P = 0.02, respectively). Conclusion The ghrelin maturation enzyme PCSK1/3 gene expression exhibited transient post-natal modifications in parallel with transient variations in circulating plasma ghrelin level in suckling piglets. Formula feeding slightly impacted GOAT mRNA level with no significant change in circulating ghrelin levels, irrespective of the type of formula tested.

Published
2019

2. Transarterial Radioembolization (TARE) Agents beyond Y-90-Microspheres

Author

Etienne Garin, Pascal Loyer, Nicolas Lepareur, Julien Edeline, Christelle Bouvry, Valérie Ardisson, Xavier Palard, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex IRON [ANR-11-LABX-0018], ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Jonchère, Laurent, and Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Tare weight, Review Article, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Transarterial Radioembolization, serum-albumin microspheres, General Biochemistry, Genetics and Molecular Biology, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, Microsphere, 03 medical and health sciences, 0302 clinical medicine, internal radiation-therapy, liver-cancer, hepatic-artery injection, Carcinoma, Medicine, Animals, Humans, Yttrium Radioisotopes, poly(l-lactic acid) microspheres, inoperable hepatocellular-carcinoma, ho-166 loaded microspheres, radionuclide therapy, intraarterial injection, i-131-labeled lipiodol, Chemoembolization, Therapeutic, Cause of death, Clinical Trials as Topic, General Immunology and Microbiology, business.industry, Liver Neoplasms, General Medicine, medicine.disease, Microspheres, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Radionuclide therapy, Radiology, business
Abstract

Liver malignancies, either primary tumours (mainly hepatocellular carcinoma and cholangiocarcinoma) or secondary hepatic metastases, are a major cause of death, with an increasing incidence. Among them, hepatocellular carcinoma (HCC) presents with a dark prognosis because of underlying liver diseases and an often late diagnosis. A curative surgical treatment can therefore only be proposed in 20 to 30% of the patients. However, new treatment options for intermediate to advanced stages, such as internal radionuclide therapy, seem particularly attractive. Transarterial radioembolization (TARE), which consists in the use of intra-arterial injection of a radiolabelled embolising agent, has led to very promising results. TARE with 90Y-loaded microspheres is now becoming an established procedure to treat liver tumours, with two commercially available products (namely, SIR-Sphere® and TheraSphere®). However, this technology remains expensive and is thus not available everywhere. The aim of this review is to describe TARE alternative technologies currently developed and investigated in clinical trials, with special emphasis on HCC.

Published
2018

3. A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and 90Y-loaded glass microsphere selective internal radiation therapy

Author

March Pracht, Vanessa Brun, Thomas Uguen, Etienne Garin, Habiba Mesbah, Yan Rolland, Xavier Palard, Astride Lievre, Sophie Laffont, Laurence Lenoir, Laure-Anne Haumont, Samuel Le Sourd, Vincent Manceau, Karim Boudjema, Julien Edeline, CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 35, Ligue Contre le Cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)

Subjects
medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Context (language use), Gastroenterology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Dosimetry, medicine, Radiology, Nuclear Medicine and imaging, Intahepatic cholangiocarcinoma, Radioembolization, Prospective cohort study, 90Y, Intrahepatic Cholangiocarcinoma, Univariate analysis, Chemotherapy, business.industry, Selective internal radiation therapy, General Medicine, medicine.disease, Microspheres, 3. Good health, 030220 oncology & carcinogenesis, Toxicity, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract

International audience; Purpose: Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context.Methods: We retrospectively studied data from 40 patients treated at our institution with 90Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis.Results: We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3-4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7 months and median overall survival (OS) was 28.6 months. Median OS was 52.7 months for patients with Child-Pugh A5 status.Conclusions: When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm.

Published
2018

4. An essential role for insulin and IGF1 receptors in regulating Sertoli cells proliferation, testis size and FSH action in mice

Author

Florence Aubry, Bernard Jégou, Jean-Luc Pitetti, François P. Pralong, Pierre Calvel, Christopher R. Cederroth, Betty Fumel, Céline Zimmermann, Michel Crausaz, Pedro Luis Herrera, Florian Guillou, Béatrice Conne, Marilena D. Papaioannou, Mylène Docquier, Marc Germond, Serge Nef, Françoise Urner, Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), 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), Centre for Medically Assisted Procreation, Fondation pour l'Andrologie, la Biologie et l'Endocrinologie de la Reproduction (FABER), Fondation F.A.B.E.R., Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), National Center of Competence in Research 'Frontiers in Genetics', University of Geneva [Switzerland], Department of Internal Medicine, University Hospital, Etude sur la Reproduction chez l'Homme et le Mammifere, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), National Centers of Competence in Research Frontiers in Genetics, the Département de l'Instruction Publique of the State of Geneva, Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Le Corre, Morgane, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1)

Subjects
Male, medicine.medical_treatment, Sertoli cell proliferation, Cell Count, Receptor, IGF Type 1, Mice, 0302 clinical medicine, Endocrinology, ddc:576.5, Receptor, Original Research, 0303 health sciences, integumentary system, Leydig Cells, Cell Differentiation, Organ Size, General Medicine, Seminiferous Tubules, Sertoli cell, Spermatozoa, medicine.anatomical_structure, Female, Signal transduction, Germ cell, Signal Transduction, Thyroid Hormones, medicine.medical_specialty, endocrine system, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Fetus, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Spermatogenesis, Cell Shape, Molecular Biology, Cell Proliferation, 030304 developmental biology, Insulin-like growth factor 1 receptor, Sertoli Cells, Gene Expression Profiling, Insulin, Receptor, Insulin, Mice, Inbred C57BL, Insulin receptor, Germ Cells, Mutation, biology.protein, Follicle Stimulating Hormone, Proto-Oncogene Proteins c-akt
Abstract

Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.

Published
2013
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5. Prostate whole-mount histology reconstruction and registration to MRI for correlating in-vivo observations with biological findings

Author

Alain Fautrel, Romain Mathieu, Frederic Commandeur, Pascal Haigron, Renaud de Crevoisier, K. Gnep, Oscar Acosta, Antoine Simon, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hépatotoxicité et xénobiotiques, Détoxication et réparation Tissulaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Prostate cancer, In vivo, Prostate, Diagnosis, Image Processing, Computer-Assisted, Medicine, Humans, Prospective Studies, Cancer, Whole mount, Prostatectomy, medicine.diagnostic_test, business.industry, Histological Techniques, Prostatic Neoplasms, Magnetic resonance imaging, Histology, Clinical routine, medicine.disease, Magnetic Resonance Imaging, 3. Good health, images, medicine.anatomical_structure, specimens, histopathology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, business, Algorithms
Abstract

International audience; Multi-parametric magnetic resonance imaging (mMRI) is the standard exam for prostate cancer diagnosis, staging and risk assessment in current clinical routine. Correlating mMRI in-vivo observations with biological findings from radical prostatectomy specimen would improve the optimal therapy selection. Thus, we proposed a method for reconstructing and registering the prostate whole-mount histology (WMH) to the MRI, considering a thin slicing of the prostatectomy specimen. The method was evaluated on 3 patients, included in a prospective study, for which hematein-eosin-safran and immunohistochemistry stainings were performed. The registration error was assessed by measuring the Euclidean distance between landmarks, previously identified by an expert on both mMRI and histological slices. The mean error was 4.90 +/- 1.34 mm. Our method demonstrated promising results for registering prostate WMH to in-vivo mMRI, thus allowing for spatial accurate correlation between radiologic observations and biological information

Published
2016

6. Complex dynamics for the study of neural activity in the human brain

Author

Garnier, Aurélie, Huneau, Clément, Vidal, Alexandre, Wendling, Fabrice, Benali, Habib, Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiopathologie des Maladies Cérébro-Vasculaires (U1161 / UMR_S 1161), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques et Modélisation d'Evry, Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), 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), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Pierre et Marie Curie - Paris 6 (UPMC), Génétique et Physiopathologie des Maladies Cérébro-Vasculaires, Université Sorbonne Paris Cité (USPC) - Université Paris Diderot - Paris 7 (UP7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA) - Université d'Evry-Val d'Essonne - ENSIIE - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de Rennes 1 (UR1), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Frouin, Frédérique

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, Quantitative Biology::Neurons and Cognition, Modeling, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Simulation
Abstract

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM).; National audience; Neural mass modeling is a part of computational neuroscience that was developed to study the general behavior of interacting neuronal populations. This type of mesoscopic model is able to generate output signals that are comparable with experimental data such as electroencephalograms. Classically, neural mass models consider two interconnected populations. One interaction have been modeled in two differents ways. In this work we propose and analyze a neural mass model embedding both approaches and compare the generated time series to real data.

Published
2015

7. Impact of sacubitril/valsartan on systolic heart failure: Right heart location and clustering analysis

Author

bouali yanis, Galli elena, paven elise, LAURIN clement, hubert arnaud, oger emmanuel, Erwan Donal, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), and Jonchère, Laurent

Subjects
Male, 030213 general clinical medicine, heart failure, Medicine (miscellaneous), Ventricular Function, Left, valsartan, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Cluster Analysis, Humans, Pharmacology (medical), Prospective Studies, sacubitril, right heart, Genetics (clinical), Aged, remodeling, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Aminobutyrates, Biphenyl Compounds, Stroke Volume, Middle Aged, 3. Good health, Drug Combinations, Reviews and References (medical), Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Heart Failure, Systolic, clustering
Abstract

International audience; Background. Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous syndrome. In heart failure (HF) classifications, right ventricle (RV) function was for a long time unrecognized in favor of left ventricular ejection fraction (LVEF). The response to sacubitril/valsartan might differ according to phenotypes and the impact of right ventricular characteristics on this response remains controversial. Objectives. First, we applied clustering analysis in a HFrEF population undergoing sacubitril/valsartan treatment according to guidelines, to identify phenotypes and their associated clinical outcomes. Secondly, we evaluated RV-remodeling. Materials and methods. It is a prospective, observational, single-center study conducted on 108 symptomatic patients (mean age 66 +/- 12.8 years, 22.2% women). First, the clustering analysis was applied in a HFrEF population undergoing sacubitril/valsartan treatment, according to the guidelines, in order to identify phenotypes and clinical outcomes associated with them. Secondly, we evaluated RV-remodeling. Results. Two distinct clusters were identified. Among the differences between phenotypes, RV (tricuspid annular plane systolic excursion (TAPSE) 16 +/- 4 mm compared to 19 +/- 4 mm, p < 0.001; RV free wall strain -19 +/- 5% compared to -21 +/- 4%, p = 0.046; RV fraction area change (FAC) 31 +/- 9% compared to 38 +/- 9%, p < 0.001), LV-filling pressure (E-wave deceleration time 138 (median: 41) ms compared to 180 (median: 94) ms, p < 0.001; E/e' 16.7 (median: 8.0) ms compared to 13.0 (median: 9.7) ms, p = 0.02) and creatinine level (106 +/- 34 mu mol/L compared to 90 +/- 19 mu mol/L, p = 0.002) were substantially different at the initiation of therapy. Major adverse cardiac events (MACEs) or death occurred in 38 out of 107 patients: 51.1% in cluster 1 compared to 24.2% in cluster 2 (p = 0.0074). A significant improvement in RV-functional parameters was observed under treatment. The TAPSE improved and correlated with the change in left ventricular (LV) function. Yet, it did not correlate with systolic pulmonary artery pressure (sPAP) and LV end-diastolic diameter. Conclusions. The HFrEF phenotype characterized by more severe RV dysfunction has a worse prognosis during sacubitril/valsartan therapy. Both RV-and LV functions significantly improve when the patient is treated with sacubitril/valsartan.

Published
2021

8. Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma

Author

Ahmad S. Halwani, Carlos Panizo, Iris Isufi, Alex F. Herrera, Craig Y. Okada, Elizabeth H. Cull, Bela Kis, Jorge M. Chaves, Nancy L. Bartlett, Weiyun Ai, Luis de la Cruz-Merino, Locke J. Bryan, Roch Houot, Kim Linton, Javier Briones, Ian Chau, Gottfried R. von Keudell, Hailing Lu, Adam Yakovich, Michael Chen, ter Meulen JH, Sergey Yurasov, Frank J. Hsu, Christopher R. Flowers, University of Utah, Clínica Universidad de Navarra [Pamplona], Universidad de Navarra [Pamplona] (UNAV), Yale University School of Medicine, H. Lee Moffitt Cancer Center and Research Institute, North-West University [Potchefstroom] (NWU), University of California [San Francisco] (UCSF), University of California, University of Sevilla, Augusta University, University System of Georgia (USG), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-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), Manchester University NHS Foundation Trust (MFT), Memorial Sloan Kettering Cancer Center (MSKCC), The University of Texas M.D. Anderson Cancer Center [Houston], Emory University [Atlanta, GA], Immune Design Corp., Yale School of Medicine [New Haven, Connecticut] (YSM), University of California [San Francisco] (UC San Francisco), University of California (UC), Universidad de Sevilla / University of Sevilla, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0303 health sciences, Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Antibodies, Monoclonal, Humanized, 3. Good health, Toll-Like Receptor 4, 03 medical and health sciences, 0302 clinical medicine, follicular lymphoma, Oncology, glucopyranosyl lipid A, 030220 oncology & carcinogenesis, Antineoplastic Combined Chemotherapy Protocols, Humans, TLR4, immunotherapy, pembrolizumab, Lymphoma, Follicular, 030304 developmental biology
Abstract

International audience; Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 mu g/dose, or 20 mu g/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 mu g/dose expansion. Adverse events grade >= 3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 mu g (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Published
2021

9. ESPEN guideline on hospital nutrition

Author

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

Subjects
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.

Published
2021

10. Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging

Author

Smiseth, Otto A, Morris, Daniel A, Cardim, Nuno, Cikes, Maja, Delgado, Victoria, Donal, Erwan, Flachskampf, Frank A, Galderisi, Maurizio, Gerber, Bernhard, Gimelli, Alessia, Klein, Allan L, Knuuti, Juhani, Lancellotti, Patrizio, Mascherbauer, Julia, Milicic, Davor, Seferovic, Petar, Solomon, Scott, Edvardsen, Thor, Popescu, Bogdan A, Reviewers: This document was reviewed by members of the 2018–2020 EACVI Scientific Documents Committee, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service de pathologie cardiovasculaire, Oslo University Hospital [Oslo], Charité Campus Virchow-Klinikum (CVK), University of Zagreb, Leiden University Medical Center (LUMC), Universiteit Leiden, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Uppsala University Hospital, 'Federico II' University of Naples Medical School, Cliniques universitaires St Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Fondazione Toscana Gabriele Monasterio, Cleveland Clinic, University of Turku, Université de Liège, Clinical Center of Serbia (KCS), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), 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), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical sciences, Cardio-vascular diseases, and Cardiology

Subjects
medicine.medical_specialty, Consensus, Diastole, heart failure, echocardiography, diastole, filling pressure, multimodality imaging, 030204 cardiovascular system & hematology, Ventricular Function, Left, MECHANISMS, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, diabetic cardiomyopathy, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, 030212 general & internal medicine, Heart Failure, Ejection fraction, diabetes, business.industry, Expert consensus, Stroke Volume, General Medicine, Prognosis, medicine.disease, 3. Good health, Heart failure, Screening, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, Heart failure with preserved ejection fraction
Abstract

Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF.

Published
2021

11. Selective Internal Radiation Combined with Chemotherapy Maintains the Quality of Life in Intrahepatic Cholangiocarcinomas

Author

Etienne Garin, Yan Rolland, Luc Beuzit, Camille Goislard de Monsabert, Eveline Boucher, Astrid Lièvre, Yann Touchefeu, Samuel Le Sourd, David Tougeron, Karim Boudjema, Boris Campillo-Gimenez, Isabelle Baumgaertner, Olivier Farges, Ahmet Ayav, Marc Pracht, Julien Edeline, Boris Guiu, CRLCC Eugène Marquis (CRLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CRHU Nancy, CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [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), BTG, Ligue Contre le Cancer, Université de Montpellier (UM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Jonchère, Laurent, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
vomiting, Yttrium-90, medicine.medical_treatment, insomnia, Brachytherapy, diarrhea, cisplatin, thrombocytopenia, chemotherapy, Gastroenterology, 030218 nuclear medicine & medical imaging, chemoradiotherapy, Cholangiocarcinoma, 0302 clinical medicine, Quality of life, dose response, pain, Embolization, RC254-282, clinical article, adult, gemcitabine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, yttrium 90, nausea, humanities, 3. Good health, sirtuin, aged, female, anorexia, patient-reported outcomes, 030220 oncology & carcinogenesis, liver resection, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, medicine.drug, radioembolization, medicine.medical_specialty, Nausea, patient-reported outcome, Article, multiple cycle treatment, 03 medical and health sciences, male, Internal medicine, biliary tract cancer, medicine, follow up, neutropenia, Humans, human, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Cisplatin, loss of appetite, Chemotherapy, business.industry, questionnaire, constipation, dyspnea, Gemcitabine, Radiation therapy, phase 2 clinical trial, multicenter study, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Concomitant, microsphere, Quality of Life, fatigue, asthenia, bile duct carcinoma, business
Abstract

Background: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. Methods: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles, SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL—measured by the QLQ-C30 questionnaire—at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. Results: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. Conclusions: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.

Published
2021

12. The European Cardiac Arrhythmia Genetics (ECGen) Focus Group

Author

Elijah R. Behr, Carol Ann Remme, Christophe Leclercq, Cardiology, ACS - Heart failure & arrhythmias, APH - Methodology, Amsterdam UMC, Laboratoire Traitement du Signal et de l'Image (LTSI), 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), St George’s University Hospitals, Amsterdam UMC - Amsterdam University Medical Center, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, medicine.medical_specialty, business.industry, Cardiac arrhythmia, Arrhythmias, Cardiac, Focus Groups, 030204 cardiovascular system & hematology, Focus group, Defibrillators, Implantable, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cardiology, Humans, Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2021

13. Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension

Author

Vincent Cottin, David Montani, Jérémie Pichon, Martine Reynaud-Gaubert, Xavier Jaïs, Pascal Magro, Gérald Simonneau, Florence Parent, Fabrice Bauer, Marianne Riou, Laurent Bertoletti, Pamela Moceri, Ari Chaouat, Andrei Seferian, Antoine Beurnier, Sébastien Renard, Pierre Mauran, Delphine Horeau-Langlard, Pascal de Groote, Laurent Savale, Mitja Jevnikar, Sophie Bulifon, Pascal Roblot, Hélène Bouvaist, Yuanchao Feng, Patrice Poubeau, Sylvain Palat, Zhiying Liang, Emmanuel Bergot, François Picard, Etienne-Marie Jutant, C. Chabanne, Olivier Sitbon, Athénaïs Boucly, Grégoire Prévot, Jean-François Mornex, Cécile Tromeur, Marc Humbert, Bruno Degano, Claire Dauphin, Arnaud Bourdin, Olivier Sanchez, Nicolas Favrolt, Jason Weatherald, Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), CHU Pontchaillou [Rennes], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Calgary, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Nord Laennec [CHU Nantes], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Reims (CHU Reims), American Memorial Hospital (Hôpital des enfants) [Reims], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Hôpital Dupuytren [CHU Limoges], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Nouvel Hôpital Civil de Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and MORNET, Dominique

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, medicine.disease, survival, Pulmonary hypertension, 3. Good health, [SDV] Life Sciences [q-bio], pulmonary arterial hypertension, Internal medicine, pulmonary hypertension, Long term survival, therapeutics, Cardiology, Medicine, Initial treatment, business
Abstract

International audience; Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Published
2021

14. Oral Health Disorders in Parkinson’s Disease: More than Meets the Eye

Author

Marc Vérin, Manon Auffret, Vincent Meuric, Emile Boyer, Martine Bonnaure-Mallet, CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Institut des Neurosciences Cliniques de Rennes (INCR), 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), This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and 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)

Subjects
medicine.medical_specialty, Parkinson's disease, Isolation (health care), [SDV]Life Sciences [q-bio], Disease, Review, Anxiety, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Quality of life, Tremor, medicine, microbiota, Humans, Intensive care medicine, Depression (differential diagnoses), dentistry, business.industry, Parkinson Disease, 030206 dentistry, medicine.disease, 3. Good health, Malnutrition, Dyskinesia, interdisciplinary research, Parkinson’s disease, Quality of Life, oral health, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, stomatognathic diseases
Abstract

International audience; Despite clinical evidence of poor oral health and hygiene in Parkinson’s disease (PD) patients, the mouth is often overlooked by both patients and the medical community, who generally focus on motor or psychiatric disorders considered more burdensome. Yet, oral health is in a two-way relationship with overall health-a weakened status triggering a decline in the quality of life. Here, we aim at giving a comprehensive overview of oral health disorders in PD, while identifying their etiologies and consequences. The physical (abnormal posture, muscle tone, tremor, and dyskinesia), behavioral (cognitive and neuropsychiatric disorders), and iatrogenic patterns associated with PD have an overall detrimental effect on patients’ oral health, putting them at risk for other disorders (infections, aspiration, pain, malnutrition), reducing their quality of life and increasing their isolation (anxiety, depression, communication issues). Interdisciplinary cooperation for prevention, management and follow-up strategies need to be implemented at an early stage to maintain and improve patients’ overall comfort and condition. Recommendations for practice, including (non-)pharmacological management strategies are discussed, with an emphasis on the neurologists’ role. Of interest, the oral cavity may become a valuable tool for diagnosis and prognosis in the near future (biomarkers). This overlooked but critical issue requires further attention and interdisciplinary research.

Published
2021

15. MLN51 triggers P-body disassembly and formation of a new type of RNA granules

Author

Annie Cavalier, Edouard Bertrand, Reynald Gillet, Pascale Bellaud, Alain Fautrel, Florence Godey, Aurélie Baguet, Nicolas Cougot, Catherine Tomasetto, Daniel Thomas, Elisabeth Daguenet, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Plate-forme d'histopathologie, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Hépatotoxicité et xénobiotiques, Détoxication et réparation Tissulaire, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -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 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Biologie, CRLCC Eugène Marquis ( CRLCC ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis (CRLCC), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
0303 health sciences, Messenger RNA, [SDV.GEN]Life Sciences [q-bio]/Genetics, RNA, Cancer, Cell Biology, Biology, medicine.disease, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Stress granule, Cytoplasm, 030220 oncology & carcinogenesis, P-bodies, medicine, Exon junction complex, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Lymph node, 030304 developmental biology
Abstract

International audience; Metastatic Lymph Node 51 (MLN51) is a core component of the exon junction complex (EJC), which is loaded on spliced mRNAs and plays an essential role in their fate. Unlike the three other EJC core components (eIF4AIII, Magoh and Y14), MLN51 is mainly located in the cytoplasm where it plays a key role in stress granules assembly. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements, and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in PB count is also observed in human HER2+ breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation may correlate to cancer progression.

Published
2014

16. Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation

Author

Nicolas Massart, James T. Ross, Erwan Flecher, Alexandre Mansour, Yoann Launey, Vincent Auffret, Claude Ecoffey, Jean-Philippe Verhoye, Nicolas Nesseler, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), 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), University of California [San Francisco] (UCSF), University of California, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)

Subjects
medicine.medical_treatment, Shock, Cardiogenic, Critical Care and Intensive Care Medicine, Lower risk, Extracorporeal, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Extracorporeal membrane oxygenation, medicine, Humans, Cardiac Surgical Procedures, Retrospective Studies, Mechanical ventilation, business.industry, Hazard ratio, 030208 emergency & critical care medicine, Retrospective cohort study, Odds ratio, Oxygenation, 3. Good health, 030228 respiratory system, Anesthesia, Airway Extubation, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract

International audience; OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

Published
2021

17. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Author

Mathurin Fumery, Jérôme Filippi, Vered Abitbol, Amélie Biron, David Laharie, Melanie Serrero, Romain Altwegg, Yoram Bouhnik, Laurent Peyrin‐Biroulet, Cyrielle Gilletta, Xavier Roblin, Guillaume Pineton de Chambrun, Lucine Vuitton, Anne Bourrier, Stephane Nancey, Jean‐Marc Gornet, Stephane Nahon, Guillaume Bouguen, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Franck Brazier, Clara Yzet, Xavier Hebuterne, Guillaume Cadiot, Hedia Brixi, Pauline Rivière, Florian Poullenot, Xavier Treton, Carmen Stefanescu, Camille Zallot, Laurent Beaugerie, Philippe Seksik, Harry Sokol, Julien Kirchgesner, Gilles Boschetti, Bernard Flourié, Claire Gay, Pauline Danion, Chloe Venturin, Matthieu Allez, Clotilde Baudry, Benjamin Pariente, Pauline Wils, Charlotte Gagnière, Jenny Tannoury, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], CHU Marseille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, CHI Créteil, GETAID, Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and 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)

Subjects
Adult, Male, medicine.medical_specialty, Pancolitis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Ustekinumab, Humans, Medicine, Pharmacology (medical), Adverse effect, Colectomy, Hepatology, business.industry, Remission Induction, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug, Cohort study
Abstract

International audience; Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. Aims To assess the real-world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score

Published
2021

18. Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates

Author

Virginie Le Rolle, Arnaud Hubert, Cecilia Linde, Martin Penicka, Emmanuel Oger, Otto A. Smiseth, Elena Galli, Jens-Uwe Voigt, Alfredo Hernandez, John M Aalen, Christophe Leclercq, Alban Gallard, Elif Sade, C K Larsen, Erwan Donal, Jürgen Duchenne, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), University of Oslo (UiO), Oslo University Hospital [Oslo], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Başkent University Hospital [Adana, Turkey], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), OLV Ziekenhuis [Aslst], Karolinska Institutet [Stockholm], Centre for Cardiological Innovation, Norwegian Health Association, South-Eastern Norway Regional Health Authority, OT12/084, University Leuven, FKM1832917N, Research Foundation Flanders, Novartis, Bayer, Astra Zeneca, Medtronic, Radiodiagnostics, and Impulse Dynamics, The University Hospital of Rennes receives research facilities from GE Healthcare, Jonchère, Laurent, 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), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)

Subjects
medicine.medical_specialty, medicine.medical_treatment, Heart Ventricles, Diastole, Cardiac resynchronization therapy, Left atrium, cardiac resynchronization therapy, heart failure, 030204 cardiovascular system & hematology, Independent predictor, Left atrial strain, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Heart Atria, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Ejection fraction, Heart Murmurs, left atrial strain, business.industry, General Medicine, medicine.disease, medicine.anatomical_structure, Treatment Outcome, Echocardiography, Heart failure, Cardiology, cardiovascular system, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business
Abstract

Aims The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT. Methods and results Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = −0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = −0.14, P = 0.049 and r = −0.17, P = 0.002, respectively). Conclusion CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.

Published
2022

19. Transient Elastography Accurately Screens for Compensated Advanced Chronic Liver Disease in Patients with Ongoing or Recent Alcohol Withdrawal

Author

Legros, Ludivine, Bardou-Jacquet, Edouard, Turlin, Bruno, Michalak, Sophie, Hamonic, Stéphanie, Le Gruyer, Antonia, Aziz, Karim, Lemoine, Cynthia, Bouvard, Nicole, Chavagnat, Jean-Jacques, Silvain, Christine, Kerjean, Jacqueline, Le Dréau, Gérard, Lacave-Oberti, Natacha, Oberti, Frederic, Le Lan, Caroline, Guyader, Dominique, Moirand, Romain, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU de Saint-Brieuc, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CH de Lorient, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), The authors acknowledge the Centre de Ressources Biologiques Santé of Rennes BB-0033-00056 for managing the patient samples., 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), and Jonchère, Laurent

Subjects
[SDV] Life Sciences [q-bio], Alcoholism, elasticity imaging techniques, Liver, Liver Diseases, liver cirrhosis, [SDV]Life Sciences [q-bio], alcohol withdrawal, Humans, Substance Withdrawal Syndrome, alcoholic liver disease, liver fibrosis
Abstract

International audience; BACKGROUND AND AIMS: Liver stiffness measurement by transient elastography (TE) is a promising method for staging fibrosis in alcohol-related liver disease, but uncertainties remain regarding the influence of alcohol consumption and thus the ideal timing for TE performance. We evaluated the performance of TE compared with liver biopsy to exclude compensated advanced chronic liver disease (cACLD) in patients hospitalized for alcohol detoxification. METHODS: Patients were prospectively recruited at six in-patient addiction centers in France. Eligible patients exhibited increased aspartate-amino-transferases, and no history or signs of overt cirrhosis. TE, histology, and biochemistry measurements were obtained within a median of 6 days after alcohol withdrawal. TE and biochemistry were repeated one and two months later. RESULTS: The study included 259 patients for per-protocol analysis, of whom 45 (17.4%) had cACLD. TE identified patients with high accuracy at inclusion, 1-, and 2-month follow up, with area under curve values of 0.96 [95% confidence interval, CI, 0.94-0.99], 0.96 [95% CI, 0.92-0.99], and 0.93 [95% CI, 0.85-1.00], respectively. In 84% of patients, cACLD was ruled out when liver stiffness was 25 kPa (positive predictive value, 93% [83-102%]). Algorithms based on transaminases and/or bilirubin did not add to diagnostic performance of TE in this period. Among patients with initial liver stiffness of 10-25 kPa, over half of those with no cACLD exhibited liver stiffness of

Published
2022

20. New psychoactive substance cocktail in an intensive care intoxication case elucidated by molecular networking

Author

Pierre-Jean Ferron, Loic Grandin, Isabelle Morel, Brendan Le Daré, Thomas Gicquel, Romain Pelletier, Aurélien Couette, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), No funding to declare., Jonchère, Laurent, 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Adult, Male, Drug, Arylcyclohexylamine, Critical Care, Substance-Related Disorders, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Urine, Pharmacology, Toxicology, Mass Spectrometry, law.invention, 03 medical and health sciences, 0302 clinical medicine, intoxication, ketamine derivatives, law, Intensive care, medicine, Humans, Ketamine, 030212 general & internal medicine, Phencyclidine, intensive care, media_common, Psychotropic Drugs, molecular networking, business.industry, 030208 emergency & critical care medicine, General Medicine, Intensive care unit, 3. Good health, Substance Abuse Detection, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, New psychoactive substances, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Molecular networking, business, Chromatography, Liquid, medicine.drug
Abstract

International audience; Background The recreational use of new psychoactive substances (NPS) is increasing worldwide. Among them, the arylcyclohexylamine family including phencyclidine (PCP) and ketamine derivatives is increasing. We report a non-fatal intoxication mainly due to arylcyclohexylamine compounds illustrated by molecular networking (MN). Case details A 37-year-old man with a history of drug abuse was discovered with several bags labeled as research chemicals around him and traces of powder on his nose. He was rehydrated, intubated, and admitted to the intensive care unit (ICU). Urine and drug were analyzed by liquid chromatography-mass spectrometry for NPS identification. Several NPS were quantified in urine: 3-OH-PCP at 12,085 mg/L, 3-MeO-PCP at 1100 mg/L, 2F-DCK at 147 mg/L, N-ethylhexedrone at 165 mg/L and CMC at 48 mg/L. Using a bioinformatic approach, a molecular network was built to confirm the consumption of powders contained in the bags by comparison with patient's urine. Discussion This case illustrates the interest of MN to (i) perform sample-to-sample comparison, (ii) target quantification methods, and (iii) allow proper management to confirm the relevance of the treatment.

Published
2021

21. Les limites de l’ECG du sportif

Author

F. Schnell, Laboratoire Traitement du Signal et de l'Image (LTSI), 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), CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030229 sport sciences, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2021

22. Iron and platelets: A subtle, under‐recognized relationship

Author

Eolia Brissot, Pierre Brissot, Marie-Bérengère Troadec, Olivier Loréal, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Nutrition, Métabolismes et Cancer (NuMeCan), 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), None, Jonchère, Laurent, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Blood Platelets, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Iron, 03 medical and health sciences, 0302 clinical medicine, Megakaryocyte, Internal medicine, medicine, Humans, Platelet, Thrombopoiesis, Hemochromatosis, Thrombocytosis, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, medicine.anatomical_structure, Endocrinology, Iron-deficiency anemia, 030220 oncology & carcinogenesis, Hepatic fibrosis, business, 030215 immunology
Abstract

No data; International audience; The role of iron in the formation and functioning of erythrocytes, and to a lesser degree of white blood cells, is well established, but the relationship between iron and platelets is less documented. Physiologically, iron plays an important role in hematopoiesis, including thrombopoiesis; iron levels direct, together with genetic factors, the lineage commitment of megakaryocytic/erythroid progenitors toward either megakaryocyte or erythroid progenitors. Megakaryocytic iron contributes to cellular machinery, especially energy production in platelet mitochondria. Thrombocytosis, possibly favoring vascular thrombosis, is a classical feature observed with abnormally low total body iron stores (mainly due to blood losses or decreased duodenal iron intake), but thrombocytopenia can also occur in severe iron deficiency anemia. Iron sequestration, as seen in inflammatory conditions, can be associated with early thrombocytopenia due to platelet consumption and followed by reactive replenishment of the platelet pool with possibility of thrombocytosis. Iron overload of genetic origin (hemochromatosis), despite expected mitochondrial damage related to ferroptosis, has not been reported to cause thrombocytopenia (except in case of high degree of hepatic fibrosis), and iron-related alteration of platelet function is still a matter of debate. In acquired iron overload (of transfusional and/or dyserythropoiesis origin), quantitative or qualitative platelet changes are difficult to attribute to iron alone due to the interference of the underlying hematological conditions; likewise, hematological improvement, including increased blood platelet counts, observed under iron oral chelation is likely to reflect mechanisms other than the sole beneficial impact of iron depletion.

Published
2021

23. Early Detection of Late Onset Sepsis in Premature Infants Using Visibility Graph Analysis of Heart Rate Variability

Author

Patrick Pladys, Cristhyne Leon, Christelle Leon, Alain Beuchée, Carrault Guy, Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Grant agreement No. 689260, European Unions Horizon 2020 research and innovation program, Jonchère, Laurent, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Pediatrics, medicine.medical_specialty, predictive monitoring, premature infants, Feature selection, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Heart Rate, Intensive Care Units, Neonatal, Sepsis, Intensive care, Heart rate, medicine, Humans, Heart rate variability, 030212 general & internal medicine, Electrical and Electronic Engineering, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Receiver operating characteristic, Visibility graph, Infant, Newborn, Infant, late onset sepsis, visibility graph, 3. Good health, Computer Science Applications, Early Diagnosis, machine learning, Visibility graph analysis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Infant, Premature, 030217 neurology & neurosurgery, Biotechnology
Abstract

International audience; Objective: This study was designed to test the diagnostic value of visibility graph features derived from the heart rate time series to predict late onset sepsis (LOS) in preterm infants using machine learning. Methods: The heart rate variability (HRV) data was acquired from 49 premature newborns hospitalized in neonatal intensive care units (NICU). The LOS group consisted of patients who received more than five days of antibiotics, at least 72 hours after birth. The control group consisted of infants who did not receive antibiotics. HRV features in the days prior to the start of antibiotics (LOS group) or in a randomly selected period (control group) were compared against a baseline value calculated during a calibration period. After automatic feature selection, four machine learning algorithms were trained. All the tests were done using two variants of the feature set: one only included traditional HRV features, and the other additionally included visibility graph features. Performance was studied using area under the receiver operating characteristics curve (AUROC). Results: The best performance for detecting LOS was obtained with logistic regression, using the feature set including visibility graph features, with AUROC of 87.7% during the six hours preceding the start of antibiotics, and with predictive potential (AUROC above 70%) as early as 42 h before start of antibiotics. Conclusion: These results demonstrate the usefulness of introducing visibility graph indexes in HRV analysis for sepsis prediction in newborns. Significance: The method proposed the possibility of non-invasive, real-Time monitoring of risk of LOS in a NICU setting.

Published
2021

24. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis

Author

Massart, Julie, Robin, Marie-Anne, Noury, Fanny, Fautrel, Alain, Lettéron, P., Bado, A., Eliat, Pierre-Antoine, Fromenty, Bernard, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Hépatotoxicité et xénobiotiques, Détoxication et réparation Tissulaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Recherche Agronomique (INRA), INSERM (Institut Nationale de la Santé et de la Recherche Médicale), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Blood Glucose, Male, MESH: Inflammation, obesity, Mice, Obese, methylxanthine, Mice, Adipocytes, MESH: Obesity, MESH: Animals, glucose, MESH: Mice, Obese, MESH: Fatty Liver, MESH: Pentoxifylline, Glucose Transporter Type 2, MESH: Oxidative Stress, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Nuclear Proteins, MESH: Transcription Factors, Research Papers, Lipids, MESH: Glucose, Jejunum, Liver, MESH: Glycolysis, MESH: Sodium-Glucose Transporter 1, Sterol Regulatory Element Binding Protein 1, Glycolysis, drug-induced liver injury, MESH: Diabetes Mellitus, Type 2, MESH: Triglycerides, MESH: Cell Line, Tumor, ChREBP, MESH: Intestinal Absorption, MESH: Glucose Tolerance Test, MESH: Sterol Regulatory Element Binding Protein 1, Sodium-Glucose Transporter 1, MESH: Mice, Inbred C57BL, MESH: Transaminases, Cell Line, Tumor, Animals, Humans, MESH: Mice, Transaminases, Triglycerides, MESH: Adipocytes, fatty liver, Inflammation, MESH: Lipogenesis, MESH: Humans, Lipogenesis, MESH: Biological Markers, Glucose Tolerance Test, MESH: Lipids, MESH: Male, Mice, Inbred C57BL, Oxidative Stress, pentoxifylline, Diabetes Mellitus, Type 2, Intestinal Absorption, MESH: Jejunum, MESH: Blood Glucose, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Glucose Transporter Type 2, MESH: Nuclear Proteins, Biomarkers, Transcription Factors, MESH: Liver
Abstract

International audience; BACKGROUND AND PURPOSE: Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes. EXPERIMENTAL APPROACH: Pentoxifylline (100 mg*kg(-1) *day(-1)) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT-PCR and Western blotting. KEY RESULTS: Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline-treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver. CONCLUSION AND IMPLICATIONS: Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long-term treatment with pentoxifylline could worsen fatty liver in some patients with pre-existing hyperglycaemia.

Published
2012

25. Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial

Author

Vassilis, Tsatsaris, Catherine, Capitant, Thomas, Schmitz, Corine, Chazallon, Sophie, Bulifon, Didier, Riethmuller, Olivier, Picone, Patrice, Poulain, Fanny, Lewin, Fabrice, Lainé, Evelyne, Jacqz-Aigrain, Jean-Pierre, Aboulker, Odile, Launay, Elisabeth, Moreau, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie-obstétrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Fer et Métabolismes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), French National Institute of Health and Medical Research, programme de recherches H1N1 Aviesan, Institut de Microbiologie et des Maladies Infectieuses, Inserm C09-33 PREFLUVAC (Immunogenicity and Safety of an Inactivated Nonadjuvanted A[H1N1v] Influenza Vaccine in Pregnant Women) Study Group., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Biologie du développement et reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Centre d'Investigation Clinique [Rennes] ( CIC ), 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 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 ) -Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Prospective Studies, MESH: Maternal-Fetal Exchange, MESH : Pregnancy Trimester, Third, MESH : Pregnancy Trimester, Second, medicine.disease_cause, Antibodies, Viral, MESH: Influenza Vaccines, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, MESH: Pregnancy, Pregnancy, Influenza A virus, Medicine, MESH : Female, MESH : Influenza, Human, 030212 general & internal medicine, Prospective Studies, Pregnancy Complications, Infectious, Maternal-Fetal Exchange, 030219 obstetrics & reproductive medicine, MESH: Middle Aged, biology, MESH: Influenza, Human, MESH: Neutralization Tests, MESH: Infant, Newborn, Antibody titer, General Medicine, MESH : Adult, Middle Aged, Fetal Blood, MESH : Influenza A Virus, H1N1 Subtype, 3. Good health, Vaccination, Titer, Influenza Vaccines, MESH: Young Adult, MESH: Hemagglutination Inhibition Tests, Pregnancy Trimester, Second, MESH: Pregnancy Trimester, Second, MESH: Pregnancy Trimester, Third, Gestation, Female, Antibody, MESH : Antibodies, Viral, Adult, medicine.medical_specialty, Adolescent, Pregnancy Trimester, Third, MESH : Young Adult, MESH : Neutralization Tests, MESH : Infant, Newborn, MESH: Influenza A Virus, H1N1 Subtype, 03 medical and health sciences, Young Adult, Neutralization Tests, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Influenza, Human, Internal Medicine, Humans, MESH : Middle Aged, MESH: Pregnancy Complications, Infectious, MESH: Fetal Blood, Seroconversion, MESH : Fetal Blood, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Infant, Newborn, MESH : Maternal-Fetal Exchange, MESH: Adult, Hemagglutination Inhibition Tests, medicine.disease, MESH : Hemagglutination Inhibition Tests, MESH : Influenza Vaccines, MESH: Prospective Studies, MESH : Pregnancy, MESH : Pregnancy Complications, Infectious, Immunology, biology.protein, business, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND: Pregnant women and infants who get influenza are at increased risk for severe illness. OBJECTIVE: To evaluate the immunogenicity and transplacental antibody transfer of 2009 pandemic influenza A(H1N1) vaccine administered during pregnancy. DESIGN: Prospective, multicenter, single-group clinical trial. (ClinicalTrials.gov registration number: NCT01024400) SETTING: Five level-3 perinatal centers in France. PATIENTS: 107 pregnant women between 22(0/7) and 32(0/7) weeks of gestation. INTERVENTION: An intramuscular dose of a nonadjuvanted H1N1 vaccine that contained 15 mcg of hemagglutinin. MEASUREMENTS: Proportion of women with an influenza antibody titer of 1:40 or greater at days 21 and 42 after vaccination, delivery, and 3 months after delivery. Seroconversion rate, fold increase in the geometric mean titer 21 days after vaccination, and proportion of neonates with an antibody titer of 1:40 or greater at birth were also assessed. RESULTS: At baseline, 19% of the women had an antibody titer of 1:40 or greater. At day 21, 98% of the women had an antibody titer of 1:40 or greater, the seroconversion rate was 93%, and the fold increase in geometric mean titer was 67.4. At day 42, delivery, and 3 months after delivery, 98%, 92%, and 90% of the women, respectively, had an antibody titer of 1:40 or greater. Ninety-five percent of the cord serum samples obtained from 88 neonates showed an antibody titer of 1:40 or greater. The median neonate-mother antibody titer ratio was 1.4. LIMITATIONS: Only healthy pregnant women were selected. Data on hemagglutination inhibition antibody titers of infants were reported only at birth. CONCLUSION: A single dose of a nonadjuvanted influenza A(H1N1) vaccine with 15 mcg of hemagglutinin triggered a strong immune response in pregnant women and a high rate of neonatal seroprotection. PRIMARY FUNDING SOURCE: French National Institute of Health and Medical Research.

Published
2011

26. Loss of Dicer in Sertoli cells has a major impact on the testicular proteome of mice

Author

Charles E. Vejnar, Marguerite Neerman-Arbez, Charles Pineau, Antoine Rolland, Olivier Schaad, Serge Nef, Marilena D. Papaioannou, Florian Guillou, Alexandre Fort, Mélanie Lagarrigue, Patrick Descombes, Evgeny M. Zdobnov, Florence Aubry, Françoise Kühne, Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Virus, Environnement et Reproduction, Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-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)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics-Swiss Institute of Bioinformatics, Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-IFR140-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Genomics Platform, University of Geneva [Switzerland]-National Center of Competence in Research ‘Frontiers in Genetics', Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), 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)-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)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Université de Lausanne = University of Lausanne (UNIL), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE)-National Center of Competence in Research ‘Frontiers in Genetics', Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Superoxide Dismutase/genetics/metabolism, Enzymologic, Ribonuclease III, Male, Transcription, Genetic, Proteome, Ribonuclease III/deficiency/genetics, Proteome/metabolism, Inbred C57BL, Biochemistry, Transgenic, Analytical Chemistry, Mice, Superoxide Dismutase-1, MESH: Ribonuclease III, Genes, Reporter, Luciferases, Firefly, RNA interference, Tandem Mass Spectrometry, Testis, MESH: Up-Regulation, ddc:576.5, MESH: Animals, Promoter Regions, Genetic, Luciferases, Luciferases, Firefly/biosynthesis/genetics, 3' Untranslated Regions, MESH: Superoxide Dismutase, Sequence Deletion, Regulation of gene expression, 0303 health sciences, MESH: Testis, MESH: Gene Expression Regulation, Enzymologic, Testis/metabolism/pathology, 030302 biochemistry & molecular biology, MESH: 3' Untranslated Regions, MESH: Sequence Deletion, Sertoli cell, Up-Regulation, MESH: Proteome, medicine.anatomical_structure, RNA Interference, Transcription, Germ cell, MESH: Mice, Transgenic, MESH: RNA Interference, Mice, Transgenic, Biology, Gene Expression Regulation, Enzymologic, Promoter Regions, MicroRNAs/genetics/metabolism, 03 medical and health sciences, MESH: Gene Expression Profiling, Genetic, MESH: Sertoli Cells, MESH: Mice, Inbred C57BL, microRNA, MESH: Promoter Regions, Genetic, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Firefly, Reporter, MESH: Mice, 030304 developmental biology, Sertoli Cells, MESH: Luciferases, Firefly, Superoxide Dismutase, Research, Gene Expression Profiling, MESH: Transcription, Genetic, MESH: Genes, Reporter, MESH: Tandem Mass Spectrometry, Molecular biology, MESH: Male, Mice, Inbred C57BL, MicroRNAs, Gene Expression Regulation, Genes, biology.protein, Sertoli Cells/metabolism, Spermatogenesis, MESH: MicroRNAs, Dicer
Abstract

International audience; Sertoli cells (SCs) are the central, essential coordinators of spermatogenesis, without which germ cell development cannot occur. We previously showed that Dicer, an RNaseIII endonuclease required for microRNA (miRNA) biogenesis, is absolutely essential for Sertoli cells to mature, survive, and ultimately sustain germ cell development. Here, using isotope-coded protein labeling, a technique for protein relative quantification by mass spectrometry, we investigated the impact of Sertoli cell-Dicer and subsequent miRNA loss on the testicular proteome. We found that, a large proportion of proteins (50 out of 130) are up-regulated by more that 1.3-fold in testes lacking Sertoli cell-Dicer, yet that this protein up-regulation is mild, never exceeding a 2-fold change, and is not preceeded by alterations of the corresponding mRNAs. Of note, the expression levels of six proteins of interest were further validated using the Absolute Quantification (AQUA) peptide technology. Furthermore, through 3'UTR luciferase assays we identified one up-regulated protein, SOD-1, a Cu/Zn superoxide dismutase whose overexpression has been linked to enhanced cell death through apoptosis, as a likely direct target of three Sertoli cell-expressed miRNAs, miR-125a-3p, miR-872 and miR-24. Altogether, our study, which is one of the few in vivo analyses of miRNA effects on protein output, suggests that, at least in our system, miRNAs play a significant role in translation control.

Published
2011

27. Vaginal Pessary for Pelvic Organ Prolapse: A French Multidisciplinary Survey

Author

R. Fauvet, Renaud de Tayrac, Mathilde Martin-Lasnel, Anne Villot, A.C. Pizzoferrato, Krystel Nyangoh-Timoh, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), CH Centre Hospitalier Public du Cotentin (CHPC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Public du Cotentin (CHPC)

Subjects
Vaginal discharge, Pessary, medicine.medical_specialty, education, Urinary incontinence, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Introitus, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Surveys and Questionnaires, Health care, medicine, Humans, 030212 general & internal medicine, Survey, Aged, Pelvic organ, Practice, 030219 obstetrics & reproductive medicine, business.industry, General surgery, General Medicine, Pessaries, 3. Good health, Pelvic organ prolapse, medicine.anatomical_structure, Urinary Incontinence, Knowledge, Vagina, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business
Abstract

International audience; Objective: Pessary fitting and follow-up for women with pelvic organ prolapse (POP) can be performed by different health care practitioners (HCPs). We aimed to investigate knowledge and current practices among the main HCPs involved in pessary use in France. Materials and Methods: We sent an electronic questionnaire about pessary use to the members of eight French learned societies between April and October 2020. Results: During the study period, 1017 HCPs responded to the questionnaire: 712 (70.0%) were doctors, 208 (20.4%) physiotherapists, 95 (9.3%) midwives, and 7 (0.6%) nurses. Of the respondents, 69.1% claimed to be comfortable with pessary fitting and follow-up, and 54.1% think that a pessary can be offered as a first-line treatment in the management of POP. However, 60.1% reported that the main indications for pessaries were "older women," 71.3% for women with contraindications to surgery, and 60.5% for women waiting for surgery. 23.9% do not prescribe local estrogen therapy with a pessary for postmenopausal women. The main pessaries used are the ring and cube types (63.7 and 57.5%, respectively). Wide introitus (53.3%), difficulties of use (56.3%), a short vagina (41.4%), and major unmasked urinary incontinence (47.2%) are considered to be the main risk factors for pessary failure. The most common complications related to pessaries reported by the patients are vaginal discharge (48.6%) and pain or discomfort (40.6%). Up to 43.4% of respondents considered that a follow-up visit every 3-6 months was optimal. The need for training ranged from 42.8% for nurses to 65.2% for general practitioners. Conclusions: This national multidisciplinary survey revealed that HCPs in France are on the whole comfortable with pessaries and mainly prescribe the ring and cube form. Even if opinion about pessaries appears to be changing, HCPs would welcome additional training to improve knowledge and practices.

Published
2022

28. Hemochromatosis classification: update and recommendations by the BIOIRON Society

Author

Pierre Brissot, Ioav Cabantchik, Fabiana Busti, Domenico Girelli, Martina U. Muckenthaler, Graça Porto, Università degli studi di Verona = University of Verona (UNIVR), Nutrition, Métabolismes et Cancer (NuMeCan), 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), The Hebrew University of Jerusalem (HUJ), University of Heidelberg, Medical Faculty, Instituto de Biologia Molecular e Celular (IBMC), Jonchère, Laurent, University of Verona (UNIVR), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Molecular complexity, Iron Overload, Iron, [SDV]Life Sciences [q-bio], Immunology, MEDLINE, Bioinformatics, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Hepcidin, Humans, Medicine, Hemochromatosis Protein, Cation Transport Proteins, Hemochromatosis, 030304 developmental biology, 0303 health sciences, biology, business.industry, Genetic heterogeneity, Cell Biology, Hematology, Ferroportin disease, medicine.disease, 3. Good health, hemochromatosis, iron overload, Clinical Practice, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, biology.protein, business, Gene Discovery
Abstract

Hemochromatosis (HC) is a genetically heterogeneous disorder in which uncontrolled intestinal iron absorption may lead to progressive iron overload (IO) responsible for disabling and life-threatening complications such as arthritis, diabetes, heart failure, hepatic cirrhosis, and hepatocellular carcinoma. The recent advances in the knowledge of pathophysiology and molecular basis of iron metabolism have highlighted that HC is caused by mutations in at least 5 genes, resulting in insufficient hepcidin production or, rarely, resistance to hepcidin action. This has led to an HC classification based on different molecular subtypes, mainly reflecting successive gene discovery. This scheme was difficult to adopt in clinical practice and therefore needs revision. Here we present recommendations for unambiguous HC classification developed by a working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society), including both clinicians and basic scientists during a meeting in Heidelberg, Germany. We propose to deemphasize the use of the molecular subtype criteria in favor of a classification addressing both clinical issues and molecular complexity. Ferroportin disease (former type 4a) has been excluded because of its distinct phenotype. The novel classification aims to be of practical help whenever a detailed molecular characterization of HC is not readily available.

Published
2022

29. TGFβ-induced FOXS1 controls epithelial-mesenchymal transition and predicts a poor prognosis in liver cancer

Author

Raphael Pineau, Stefano Caruso, David Gilot, Kevin Bévant, Cédric Coulouarn, Gaëlle Angenard, Panagiotis Papoutsoglou, Matthis Desoteux, Jessica Zucman-Rossi, L Sulpice, Corentin Louis, Nutrition, Métabolismes et Cancer (NuMeCan), 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), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Supported by Fondation ARC pour la Recherche sur le Cancer, IREB, Institut National Du Cancer, Prix René and Andrée Duquesne–Comité de Paris Ligue Contre le Cancer, Coup d’Elan de la Fondation Bettencourt-Schueller, Raymond Rosen Award from the Fondation pour le Recherche Médicale, Université de Rennes 1, ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan Cancer (C18007NS), Labex OncoImmunology (Investissement d’Avenir), Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer (CD22, CD35, and CD85), Ligue Nationale Contre le Cancer, Région Bretagne, Fondation Mérieux, and SIRIC CARPEM., École pratique des hautes études (EPHE), Gestionnaire, HAL Sorbonne Université 5, 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), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), and Dublin Institute for Advanced Studies (DIAS)

Subjects
Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, SMAD, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Medicine, Humans, Epithelial–mesenchymal transition, Transcription factor, 030304 developmental biology, 0303 health sciences, Hepatology, biology, business.industry, Liver Neoplasms, Forkhead Transcription Factors, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Transforming growth factor beta, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Biomarker (medicine), Mothers against decapentaplegic, business, Transforming growth factor
Abstract

International audience; Transforming growth factor beta (TGFβ) plays a key role in tumor progression, notably as a potent inducer of epithelial-mesenchymal transition (EMT). However, all of the molecular effectors driving TGFβ-induced EMT are not fully characterized. Here, we report that forkhead box S1 (FOXS1) is a SMAD (mothers against decapentaplegic)dependent TGFβ-induced transcription factor, which regulates the expression of genes required for the initial steps of EMT (e.g., snail family transcription repressor 1) and to maintain a mesenchymal phenotype in hepatocellular carcinoma (HCC) cells. In human HCC, we report that FOXS1 is a biomarker of poorly differentiated and aggressive tumor subtypes. Importantly, FOXS1 expression level and activity are associated with a poor prognosis (e.g., reduced patient survival), not only in HCC but also in colon, stomach, and kidney cancers. Conclusion: FOXS1 constitutes a clinically relevant biomarker for tumors in which the pro-metastatic arm of TGFβ is active (i.e., patients who may benefit from targeted therapies using inhibitors of the TGFβ pathway). (Hepatology Communications 2021;0:1-15).

Published
2022

30. A common SNP near BMP2 is associated with severity of the iron burden in HFE p.C282Y homozygous patients: a follow-up study

Author

Jacqueline Milet, Yves Deugnier, Jean Mosser, Gérald Le Gac, Catherine Bourgain, Corine Thèze, Virginie Scotet, Isabelle Gourlaouen, Claude Férec, Santé de la mère et de l'enfant en milieu tropical : épidémiologie génétique et périnatale, Université Paris Descartes - Paris 5 (UPD5), Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fer et Métabolismes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes]-Centre Hospitalier Universitaire [Rennes], Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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 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)-Service des maladies du foie, De Villemeur, Hervé, Université Paris Descartes - Paris 5 ( UPD5 ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Génétique épidémiologique et structures des populations humaines ( Inserm U535 ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique [Rennes] ( CIC ), 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 Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Service des maladies du foie

Subjects
Male, Bone Morphogenetic Protein 2, Penetrance, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Gene Frequency, Phlebotomy, Genotype, 0303 health sciences, Homozygote, Penetrance of the p.C282Y/p.C282Y genotype, Hematology, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Molecular Medicine, Female, France, Hemochromatosis, Adult, Alcohol Drinking, Iron, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, SNP, Humans, Allele, Hemochromatosis Protein, Molecular Biology, Genetic Association Studies, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Histocompatibility Antigens Class I, Membrane Proteins, Cell Biology, medicine.disease, Modifier genes, Amino Acid Substitution, Ferritins, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Biomarkers, Follow-Up Studies
Abstract

International audience; BACKGROUND AND OBJECTIVES: It is now generally admitted that penetrance of the common HFE p.C282Y/p.C282Y genotype is incomplete, and identification of modifier genes is the concern of a growing number of research projects. We recently identified a significant association between pretherapeutic serum ferritin level and the common rs235756 single nucleotide polymorphism (SNP) of the BMP2 gene region. Our results further suggested an interactive effect between the BMP2 rs235756 SNP and the rs16827043 SNP in HJV, with a small additive effect of the rs4901474 SNP in BMP4. DESIGN AND METHODS: The present study has been designed as a replication study in an independent cohort of 450 HFE p.C282Y homozygous patients from a nearby French region (Brittany). Information on individual alcohol consumption and amount of iron removed by phlebotomy being available for a substantial part of this cohort, additional analyses were conducted. RESULTS: Only the use of the Amount of Iron Removed by phlebotomy (AIR) as marker of iron burden has provided positive results. Indeed, a significant association was detected between rs235756 and AIR adjusted for sex and age, with a mean AIR increasing with the number of BMP2 T alleles in the genotype groups. The effect of rs235657 was not strong enough to detect effects of gene combinations. Still, the trend in two-locus genotype risks involving BMP2 and HJV for AIR was concordant with the specific interactive effect described in the initial study. INTERPRETATION AND CONCLUSIONS: Although we failed to replicate results of the initial study, we argue that, altogether, our results help to consider genes involved in the regulation of hepcidin synthesis as potential modifiers of the p.C282Y/pC282Y genotype expression and especially BMP2.

Published
2010

31. Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

Author

Cerapio, Juan Pablo, Marchio, Agnès, Cano, Luis, López, Ignacio, Fournié, Jean-Jacques, Régnault, Béatrice, Casavilca-Zambrano, Sandro, Ruiz, Eloy, Dejean, Anne, Bertani, Stéphane, Pineau, Pascal, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), 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), Génotypage des Eucaryotes (Plate-Forme), Institut Pasteur [Paris] (IP), Instituto Nacional de Enfermedades Neoplasicas [Lima, Pérou] (INEN), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD), Alliance pour les sciences de la vie et de la santé (Aviesan)., European Project: 823935,H2020-MSCA-RISE-2018,COCLICAN(2018), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Innovation et Recherche Technologique / Center for Innovation and Technological Research, Institut Pasteur [Paris], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Bertani, Stéphane, Collaborative Consortium for the early detection of Liver Cancer - COCLICAN - - H2020-MSCA-RISE-20182018-11-01 - 2022-10-31 - 823935 - VALID, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, 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), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
DNA methylation, MESH: Cancer, [SDV]Life Sciences [q-bio], [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, indigenous people, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, [SHS.ANTHRO-BIO] Humanities and Social Sciences/Biological anthropology, MESH: Comparative Genomics, liver cancer, integrative genomics, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hepatitis B virus, Research Paper
Abstract

International audience; Hepatocellular carcinoma (HCC) usually afflicts individuals in their maturity after a protracted liver disease. Contrasting with this pattern, the age structure of HCC in Andean people displays a bimodal distribution with half of the patients developing HCC in adolescence and early adulthood. To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults. While genome-wide hypomethylation is considered as a paradigm in human HCCs, our analysis revealed that Peruvian tumors are associated with a global DNA hypermethylation. Moreover, pathway enrichment analysis of transcriptome data characterized an original combination of signatures. Peruvian HCC forgoes canonical activations of IGF2, Notch, Ras/MAPK, and TGF-β signals to depend instead on Hippo/YAP1, MYC, and Wnt/β-catenin pathways. These signatures delineate a homogeneous subtype of liver tumors at the interface of the proliferative and non-proliferative classes of HCCs. Remarkably, the development of this HCC subtype occurs in patients with one of the four Native American mitochondrial haplogroups A-D. Finally, integrative characterization revealed that Peruvian HCC is apparently controlled by the PRC2 complex that mediates cell reprogramming with massive DNA methylation modulating gene expression and pinpointed retinoid signaling as a potential target for epigenetic therapy.

Published
2021

32. Dynamic risk assessment to improve quality of care in patients with atrial fibrillation

Author

Ursula Ravens, Bushra S. Ilyas, Ulrich Schotten, Isabelle C. Van Gelder, Christian G Meyer, Burcu Vardar, Elena Andreassi Marinelli, Moritz F. Sinner, Stephan Willems, Christophe Leclercq, Renate B. Schnabel, Doreen Haase, Larissa Fabritz, Dierk Thomas, Dobromir Dobrev, Mattias Wieloch, Jeff S. Healey, Emma Svennberg, Paul D. Ziegler, Christina Easter, Stefan H. Hohnloser, Gregory Y.H. Lip, Gerhard Hindricks, A. John Camm, Andreas Goette, Monika Stoll, Irina Savelieva, Tatjana S. Potpara, Guenter Breithardt, Stéphane N. Hatem, Karl Georg Häusler, Rüdiger Smolnik, Alice J Sitch, Reza Wakili, Jan Steffel, Helmut Pürerfellner, Winnie Chua, José L. Merino, Anthony W.S. Chan, Harry J.G.M. Crijns, Thomas Huebner, Paulus Kirchhof, Christina Dimopoulou, Thorsten Lewalter, Stef Zeemering, Kenneth M. Stein, Mirko De Melis, Eduard Guasch, Jordi Heijman, Dipak Kotecha, Lluís Mont, Jonas Oldgren, Michael Nabauer, Michiel Rienstra, Ingo Kutschka, Aaron Isaacs, Lars Eckardt, Hein Heidbuchel, Cardiovascular Centre (CVC), University of Birmingham [Birmingham], University Hospitals Birmingham [Birmingham, Royaume-Uni], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Barcelona, University Hospital of Würzburg, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Belgrade [Belgrade], University Medical Center Groningen [Groningen] (UMCG), Asklepios Klinik St. Georg, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of London [London], Pfizer, Medtronic Inc [Minneapolis, MI, USA], European Society of Cardiology (ESC), University Hospital [Essen, Germany], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Population Health Research Institute [Hamilton, ON, Canada], Goethe-Universität Frankfurt am Main, University Hospital Göttingen, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Liverpool, La Paz University Hospital, Universitat de Barcelona (UB), University-Hospital Munich-Großhadern [München], Uppsala University, Ordensklinikum Linz Elisabethinen, St George's, University of London, Universität Zürich [Zürich] = University of Zurich (UZH), Boston Scientific, Karolinska Institutet [Stockholm], Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], University Hospital Essen, SANOFI Recherche, University of Antwerp (UA), Leipzig University, EHRA, 633196, EU Horizon 2020, AFNet, AFNET, MUMC+: MA Cardiologie (9), Cardiologie, RS: Carim - H01 Clinical atrial fibrillation, Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Biochemie, RS: Carim - H08 Experimental atrial fibrillation, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Technology, Quality management, Rate control, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Stroke, Research priorities, CATHETER ABLATION, ROADMAP, Integrated care, Atrial fibrillation, 3. Good health, OPPORTUNITIES, Treatment Outcome, Consensus statement, Screening, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Rhythm control, Cognitive function, Cardiology and Cardiovascular Medicine, Risk assessment, medicine.medical_specialty, Consensus, Catheter ablation, Heart failure, Outcomes, DIAGNOSIS, Risk Assessment, CLASSIFICATION, 03 medical and health sciences, Big data, Anticoagulation, FUTURE, Physiology (medical), medicine, MANAGEMENT, Humans, Intensive care medicine, Atrial cardiomyopathy, business.industry, Research, Bleeding, Quality of care, Anticoagulants, EHRA, medicine.disease, Lifestyle, AFNET, Comorbidity, PREVENTION, REDUCTION, Human medicine, business
Abstract

Aims The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. Methods and results This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. Conclusion The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

Published
2021

33. Long Noncoding RNAs in Cholangiocarcinoma

Author

Cédric Coulouarn, Panagiotis Papoutsoglou, Aude Merdrignac, 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), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Inserm, Université de Rennes 1, and ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational, [Grant C18007NS to CC]). CC is a member of the European Network for the Study of Cholangiocarcinoma (ENSCCA) and participates in the initiative COST Action EURO-CHOLANGIO-NET granted by the COST Association (CA18122)., 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), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
signaling pathway, 0301 basic medicine, Angiogenesis, Cell, information science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Epigenesis, Genetic, liver cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, parasitic diseases, medicine, Animals, Humans, cardiovascular diseases, Epigenetics, Epithelial–mesenchymal transition, Hepatology, fungi, RNA, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Long non-coding RNA, 030104 developmental biology, medicine.anatomical_structure, Bile Duct Neoplasms, Tumor progression, long non coding RNA, cardiovascular system, Cancer research, biomarker, Biomarker (medicine), RNA, Long Noncoding, 030211 gastroenterology & hepatology, cholangiocarcinoma
Abstract

International audience; Cholangiocarcinoma (CCA) is the second primary hepatic malignancy after hepatocellular carcinoma. CCA is characterized by its aggressiveness and poor prognosis associated with limited therapeutic options. Thus, a better understanding of molecular pathogenesis of CCA together with the identification of robust biomarkers and therapeutic targets is still necessary to improve the management of patients with CCA. In this review, we discuss the role of long non coding RNAs (lncRNAs) in CCA onset and progression. LncRNAs represent a heterogeneous class of RNA molecules with various genomic location and organization acting at both transcriptional and post-transcriptional levels. Notably, we provide an overview of the functions of lncRNAs in epigenetic modulation and regulation of signaling pathways and cell behaviors leading to tumor progression (e.g. apoptosis, survival, epithelial to mesenchymal transition, migration, invasion, angiogenesis). Moreover, we depict the clinical relevance of lncRNAs as biomarkers and emerging therapeutic targets in CCA.

Published
2021

34. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial

Author

Etienne Garin, Lambros Tselikas, Boris Guiu, Julia Chalaye, Julien Edeline, Thierry de Baere, Eric Assenat, Vania Tacher, Corentin Robert, Marie Terroir-Cassou-Mounat, Denis Mariano-Goulart, Giuliana Amaddeo, Xavier Palard, Antoine Hollebecque, Marilyne Kafrouni, Hélène Regnault, Karim Boudjema, Serena Grimaldi, Marjolaine Fourcade, Hicham Kobeiter, Eric Vibert, Samuel Le Sourd, Lauranne Piron, Danièle Sommacale, Sophie Laffont, Boris Campillo-Gimenez, Yan Rolland, Corentin Robert Robert, Marc Pracht, Valérie Ardisson, Laurence Lenoir, Thierry De Baere, Frederic Deschamps, Michel Ducreux, Maximiliano Gelli, Christophe Cassinotto, Carole Allimant, Sophie Bonnot-Lours, Margarita Marie, Emmanuel Itti, Lionel Lerman, Mukedaisi Abulizi, Alain Luciani, Charlotte E. Costentin, Milan Milliner, CRLCC Eugène Marquis (CRLCC), 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), Institut Gustave Roussy (IGR), Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University Hospital of Montpellier, CHU Henri Mondor, Centre Hospitalier Universitaire [Rennes], 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), 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), Département de médecine oncologique [Gustave Roussy], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Médecine nucléaire, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Henri Mondor [Créteil], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Jonchère, Laurent

Subjects
medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Clinical endpoint, Medicine, Dosimetry, Progression-free survival, education, education.field_of_study, Hepatology, business.industry, Selective internal radiation therapy, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Radiation therapy, Clinical trial, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Nuclear medicine, business
Abstract

International audience; BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma.METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion 5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group.INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

Published
2021

35. A visual analogue scale for food intake as a screening test for malnutrition in the primary care setting: Prospective non-interventional study

Author

Gwenhaël Bouëtté, Katharina Apel, Ronan Thibault, Maxime Esvan, 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), 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 Jonchère, Laurent

Subjects
Male, 0301 basic medicine, Food intake, Pediatrics, Visual Analog Scale, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, 0302 clinical medicine, Clinical endpoint, Mass Screening, Medicine, Prospective Studies, Nutritional screening, Prospective cohort study, 2. Zero hunger, Nutrition and Dietetics, Middle Aged, Primary care, 3. Good health, [SDV] Life Sciences [q-bio], Female, France, General practice, Adult, medicine.medical_specialty, Screening test, Visual analogue scale, Nutritional Status, 030209 endocrinology & metabolism, Sensitivity and Specificity, Diagnostic Self Evaluation, 03 medical and health sciences, Humans, Aged, 030109 nutrition & dietetics, Primary Health Care, business.industry, Malnutrition, Undernutrition, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, Nutrition Assessment, Non interventional, Feasibility Studies, Energy intake, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Introduction and aims:The Self-Evaluation of Food Intake (SEFI®) is a simple tool to assess food intake that correlates well with the diagnosis of malnutrition in the hospital setting. Aims: to evaluate the validity of SEFI® for the diagnosis of malnutrition among adults in the primary care setting (primary aim); to assess the prevalence of malnutrition, the feasibility of the SEFI® and the variables associated with malnutrition (secondary aims).Methods:A non-interventional prospective study on consecutive patients at three primary care practices. Primary endpoint: confrontation of a SEFI® visual analogue scale score

Published
2021

36. Les nouveaux outils d'analyse de la spermatogenèse

Author

Rolland, Antoine, Pineau, Charles, Jégou, Bernard, Virus, Environnement et Reproduction, Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), 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)-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)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-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)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-IFR140-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Brébion, Alice

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008

37. Roles of CDK/Cyclin complexes in transcription and pre-mRNA splicing: Cyclins L and CDK11 at the cross-roads of cell cycle and regulation of gene expression

Author

Janeen H. Trembley, Pascal Loyer, 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), University of Minnesota [Crookston], University of Minnesota System, 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 Jonchère, Laurent

Subjects
0301 basic medicine, Transcription, Genetic, RNA Splicing, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Cyclin-dependent kinase, Cyclins, CCNL2, RNA Precursors, CCNL1, Animals, Humans, cancer, Amino Acid Sequence, Cyclin L, Cyclin, Regulation of gene expression, biology, Kinase, Cell Cycle, Cell Biology, Cell cycle, Cyclin-Dependent Kinases, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, pre-mRNA splicing, RNA splicing, biology.protein, Phosphorylation, Transcription, 030217 neurology & neurosurgery, CDK11, Developmental Biology
Abstract

International audience; Cyclin Dependent Kinases (CDKs) represent a large family of serine/threonine protein kinases that become active upon binding to a Cyclin regulatory partner. CDK/cyclin complexes recently identified, as well as "canonical" CDK/Cyclin complexes regulating cell cycle, are implicated in the regulation of gene expression via the phosphorylation of key components of the transcription and pre-mRNA processing machineries. In this review, we summarize the role of CDK/cyclin-dependent phosphorylation in the regulation of transcription and RNA splicing and highlight recent findings that indicate the involvement of CDK11/cyclin L complexes at the cross-roads of cell cycle, transcription and RNA splicing. Finally, we discuss the potential of CDK11 and Cyclins L as therapeutic targets in cancer.

Published
2020

38. The importance of feature aggregation in radiomics: a head and neck cancer study

Author

Fontaine, Pierre, Acosta, Oscar, Castelli, Joël, de Crevoisier, Renaud, Müller, Henning, Depeursinge, Adrien, CRLCC Eugène Marquis (CRLCC), University of Applied Sciences and Arts of Western Switzerland (HES-SO), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, Adult, Adolescent, lcsh:R, lcsh:Medicine, Middle Aged, Article, Workflow, Cohort Studies, Machine Learning, Young Adult, Image processing, Head and Neck Neoplasms, Positron-Emission Tomography, Image Processing, Computer-Assisted, Humans, Computer Simulation, [SDV.IB]Life Sciences [q-bio]/Bioengineering, lcsh:Q, Tomography, X-Ray Computed, lcsh:Science, Aged, Retrospective Studies
Abstract

International audience; In standard radiomics studies the features extracted from clinical images are mostly quantified with simple statistics such as the average or variance per Region of Interest (ROI). Such approaches may smooth out any intra-region heterogeneity and thus hide some tumor aggressiveness that may hamper predictions. In this paper we study the importance of feature aggregation within the standard radiomics workflow, which allows to take into account intra-region variations. Feature aggregation methods transform a collection of voxel values from feature response maps (over a ROI) into one or several scalar values that are usable for statistical or machine learning algorithms. This important step has been little investigated within the radiomics workflows, so far. In this paper, we compare several aggregation methods with standard radiomics approaches in order to assess the improvements in prediction capabilities. We evaluate the performance using an aggregation function based on Bags of Visual Words (BoVW), which allows for the preservation of piece-wise homogeneous information within heterogeneous regions and compared with standard methods. The different models are compared on a cohort of 214 head and neck cancer patients coming from 4 medical centers. Radiomics features were extracted from manually delineated tumors in clinical PET-FDG and CT images were analyzed. We compared the performance of standard radiomics models, the volume of the ROI alone and the BoVW model for survival analysis. The average concordance index was estimated with a five fold cross-validation. The performance was significantly better using the BoVW model 0.627 (95% CI: 0.616-0.637) as compared to standard radiomics0.505 (95% CI: 0.499-0.511), mean-var. 0.543 (95% CI: 0.536-0.549), mean0.547 (95% CI: 0.541-0.554), var.0.530 (95% CI: 0.524-0.536) or volume 0.577 (95% CI: 0.571-0.582). We conclude that classical aggregation methods are not optimal in case of heterogeneous tumors. We also showed that the BoVW model is a better alternative to extract consistent features in the presence of lesions composed of heterogeneous tissue.

Published
2020

39. External validation of Gout-calculator performance on a cohort of acute arthritis (SYNOLACTATE) sparing distal joints such as hallux and midfoot. A cross-sectional study of 170 patients

Author

François Robin, Guillaume Coiffier, Olivia Berthoud, Anne Gougeon-Jolivet, Pascal Guggenbuhl, Jean-David Albert, S. Cadiou, Claude Bendavid, Nutrition, Métabolismes et Cancer (NuMeCan), 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), CHU Pontchaillou [Rennes], Centre hospitalier de Dinan, 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, Gout, [SDV]Life Sciences [q-bio], Arthritis, SYNOLACTATE, Likelihood ratios in diagnostic testing, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Gout-calculator, Rheumatology, Internal medicine, Synovial Fluid, Crystal, medicine, Humans, Synovial fluid, Prospective Studies, 030212 general & internal medicine, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Retrospective cohort study, General Medicine, medicine.disease, Uric Acid, 3. Good health, Cross-Sectional Studies, Acute arthritis, Cohort, Hallux, Septic arthritis, business
Abstract

International audience; OBJECTIVE: To evaluate the performance of the Gout-calculator in a cohort of consecutive acute arthritis affecting large and intermediate joints (without an attack on hallux or midfoot joints). METHODS: A retrospective study. Gout-calculator data were collected in medical records of patients included in the prospective consecutive cohort of acute arthritis called SYNOLACTATE. The diagnosis of gout was defined by the presence of sodium urate crystals in synovial fluid. The diagnostic performance of the Gout-calculator was studied by performing an ROC curve with the calculation of its AUC (95% CI) as well as the calculation of Sensitivity (Se), Specificity (Sp), and positive likelihood ratio (LR+). RESULTS: 170 patients with acute arthritis were included. Variables associated with the diagnosis of gout were as follows: serum uric acid > 350 μmol/L (OR 5.52 (2.52-12.1), p < 0.001), joint redness (OR 5.08 (1.85-14.0), p = 0.001), previous patient-reported arthritis attack (OR 4.04 (1.92-8.49), p < 0.001), male (OR 3.00 (1.17-7.69), p = 0.02), hypertension or cardiovascular disease (OR 2.33 (1.07-5.06), p = 0.03). The median (IQR) of Gout-calculator was significantly higher in gouty arthritis (7.0 [5.5-8.1]) than in associated-CPP acute arthritis (4.0 [2.0-5.8]), septic arthritis (3.0 [2.0-5.1]), or others arthritis (3.5 [2.0-5.5]). The AUC was 0.833 (0.768-0.897) with for the threshold ≥ 8, a Se at 27.5% (0.161-0.428), Sp 97.7% (0.934-0.992), and LR+ 11.9 (3.5-40). CONCLUSION: Despite diagnostic performances close to those published, the use of the Gout-calculator is not sufficient for the diagnosis of gout or to exclude the differential diagnosis of septic arthritis in the SYNOLACTATE cohort. KEY POINTS: • For a Gout-calculator threshold of ≤ 4, Sensitivity is 92.5%, Specificity 50.8% and LR- 0.15 to the gout diagnosis. • For a Gout-calculator threshold of > = 8, Sensitivity is 27.5%, Specificity 97.7% and LR+ 11.9 to the gout diagnosis. • In a population of acute arthritis affecting large joints, Gout-calculator is not sufficient to discriminate between gouty arthritis and septic arthritis.

Published
2020

40. Carfilzomib maintenance in newly diagnosed non-transplant eligible multiple myeloma

Author

Sophie Cereja, Damien Roos-Weil, Laurent Voillat, Marie-Odile Petillon, Véronique Dorvaux, Marie-Lorraine Chretien, Nathalie Meuleman, Hervé Avet-Loiseau, Arthur Bobin, Olivier Fitoussi, Carla Araujo, Murielle Roussel, Eric Voog, Frédérique Kuhnowski, Intergroupe Francophone du Myelome Multiple, Jean Claude Eisenmann, Mourad Tiab, Catherine Humbrecht-Kraut, Thierry Facon, Jean-Valère Malfuson, Brigitte Kolb, Karim Belhadj-Merzoug, Philippe Rodon, Pascal Bourquard, Lionel Karlin, Olivier Decaux, Maeva Kyheng, Valentine Richez, Sophie Rigaudeau, Jamile Frayfer, Xavier Leleu, Philippe Moreau, Arnaud Jaccard, Alain Duhamel, Aurore Perrot, Pascal Lenain, Cyrille Hulin, Cécile Gruchet-Merouze, Jean Fontan, Anna Schmitt, Stéphanie Guidez, Fritz Offner, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Amgen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], MEDLINE, Antineoplastic Agents, Newly diagnosed, Maintenance Chemotherapy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, business.industry, Hematology, medicine.disease, Carfilzomib, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Multiple Myeloma, business, Oligopeptides
Abstract

International audience

Published
2022

41. Classification of High Frequency Oscillations in intracranial EEG signals based on coupled time-frequency and image-related features

Author

Fatma Krikid, Ahmad Karfoul, Sahbi Chaibi, Amar Kachenoura, Anca Nica, Abdennaceur Kachouri, Régine Le Bouquin Jeannès, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Sfax - University of Sfax, 19G1411, Providence Health Care, PHC: 41711PK, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, Epilepsy, SVM, Biomedical Engineering, 020206 networking & telecommunications, Health Informatics, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Image gradient, Signal Processing, 0202 electrical engineering, electronic engineering, information engineering, Time-Frequency representation, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Sparsity, 030217 neurology & neurosurgery, High Frequency Oscillations, Multi-classification
Abstract

International audience; High Frequency Oscillations (HFOs) occurring in the range of [30–500 Hz] in epileptic intracranial ElectroEncephaloGraphic (iEEG) signals have recently proven to be good biomarkers for localizing the epileptogenic zone. Identifying these particular cerebral events and their discrimination from other transient events like interictal epileptic spikes is traditionally performed by experts through a visual inspection. However, this is laborious, very time-consuming and subjective. In this paper, a new classification approach of HFOs is proposed. This approach mainly relies on the combination of raw time frequency (TF) features, computed from a TF representation of HFOs using S-transform, with relevant image-based ones derived from a binarization of the corresponding TF grayscale image. The obtained feature vector is then used to learn a multi-class Radial Basis Function (RBF) based Support Vector Machine (SVM) classifier. The efficiency of the proposed approach, compared to conventional classification schemes based only on time, frequency or energy-based features, is confirmed, using both simulated and real iEEG signals. The proposed classification system has achieved, using simulated data and a signal to noise ratio (SNR) of 15 dB, a sensitivity, specificity, accuracy, area under the curve and F1-score around 0.990, 0.996, 0.995, 0.993 and 0.990 respectively. Besides, for real data, our proposed approach has attained the scores of 0.765, 0.941, 0.906, 0.929 and 0.768 for sensitivity, specificity, accuracy, area under the curve and F1-score respectively. These results confirm the relevance of coupling TF and image-related features, in the way proposed in this paper, for higher HFOs classification quality compared to already existing approaches. © 2021 Elsevier Ltd

Published
2022

42. Une forme de référence mutuelle pour la fusion et l'évaluation des méthodes de segmentation

Author

Jehan-Besson, S., Clouard, R., Tilmant, C., de Cesare, A., Lalande, A., Lebenberg, J., Clarysse, P., Sarry, L., Frouin, F., Garreau, M., Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Equipe Image - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)-Clermont Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
active contours, variational approaches, segmentation evaluation, shape gradients, [INFO.INFO-IT]Computer Science [cs]/Information Theory [cs.IT], Computer Science::Computer Vision and Pattern Recognition, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Mutual shape, segmentation, shape optimization, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, segmentation fusion
Abstract

This paper proposes the estimation of a mutual shape from a set of different segmentation results using both active contours and information theory. The mutual shape is here defined as a consensus shape estimated from a set of different segmentations of the same object. In an original manner, such a shape is defined as the minimum of a criterion that benefits from both the mutual information and the joint entropy of the input segmentations. This energy criterion is justified using similarities between information theory quantities and area measures, and presented in a continuous variational framework. In order to solve this shape optimization problem, shape derivatives are computed for each term of the criterion and interpreted as an evolution equation of an active contour. A mutual shape is then estimated together with the sensitivity and specificity of each segmentation. Some synthetic examples allow us to cast the light on the difference between the mutual shape and an average shape. The applicability of our framework has also been tested for segmentation evaluation and fusion of different types of real images (natural color images, old manuscripts, medical images).

Published
2022

43. Acetaminophen (APAP, paracetamol) interferes with the first trimester human fetal ovary development in an ex vivo model

Author

Laetitia L Lecante, Sabrina Leverrier-Penna, Thomas Gicquel, Frank Giton, Nathalie Costet, Christèle Desdoits-Lethimonier, Laurianne Lesné, Bernard Fromenty, Vincent Lavoué, Antoine D Rolland, Séverine Mazaud-Guittot, École des Hautes Études en Santé Publique [EHESP] (EHESP), University of Aberdeen, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), 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), CHU Pontchaillou [Rennes], 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), ANR-15-CE34-0001-01, Agence nationale de la recherche, 2014S032, Agence Nationale de Sécurité du Médicament et des Produits de Santé, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
Male, N-acetyl-p-aminophenol, hormones, paracetamol, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Biochemistry (medical), Clinical Biochemistry, Ovary, digestive, oral, and skin physiology, human fetal ovary, Endocrine Disruptors, Biochemistry, Pregnancy Trimester, First, Endocrinology, Fetus, Pregnancy, Humans, Female, metabolites, Acetaminophen
Abstract

Context Acetaminophen (APAP, paracetamol) is widely used by pregnant women. Although long considered safe, growing evidence indicates that APAP is an endocrine disruptor since in utero exposure may be associated with a higher risk of male genital tract abnormalities. In rodents, fetal exposure has long-term effects on the reproductive function of female offspring. Human studies have also suggested harmful APAP exposure effects. Objective Given that disruption of fetal ovarian development may impact women’s reproductive health, we investigated the effects of APAP on fetal human ovaries in culture. Design and Setting Human ovarian fragments from 284 fetuses aged 7 to 12 developmental weeks (DW) were cultivated ex vivo for 7 days in the presence of human-relevant concentrations of APAP (10−8 to 10−3 M) or vehicle control. Main Outcome Measures Outcomes included examination of postculture tissue morphology, cell viability, apoptosis, and quantification of hormones, APAP, and APAP metabolites in conditioned culture media. Results APAP reduced the total cell number specifically in 10- to 12-DW ovaries, induced cell death, and decreased KI67-positive cell density independently of fetal age. APAP targeted subpopulations of germ cells and disrupted human fetal ovarian steroidogenesis, without affecting prostaglandin or inhibin B production. Human fetal ovaries were able to metabolize APAP. Conclusions Our data indicate that APAP can impact first trimester human fetal ovarian development, especially during a 10- to 12-DW window of heightened sensitivity. Overall, APAP behaves as an endocrine disruptor in the fetal human ovary.

Published
2022

44. Natural History of Perianal Crohn's Disease: Long-term Follow-up of a Population-Based Cohort

Author

Charlène Brochard, Marie-Laure Rabilloud, Stéphanie Hamonic, Emma Bajeux, Maël Pagenault, Alain Dabadie, Agathe Gerfaud, Jean-François Viel, Isabelle Tron, Michel Robaszkiewicz, Jean-François Bretagne, Laurent Siproudhis, Guillaume Bouguen, Etienne Cruchant, Jean-Luc Alexandre, Jacques Arnaud Seyrig, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), 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), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Observatoire Régional de Santé (ORS Bretagne), ORS Bretagne, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AbbVie, 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), 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, outcomes, population based, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, medicine, Humans, Rectal Fistula, Proctitis, Retrospective Studies, Crohn's disease, Hepatology, business.industry, Incidence (epidemiology), Hazard ratio, Gastroenterology, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Natural history, [SDV] Life Sciences [q-bio], natural history, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Perianal Crohn’s disease, Anal stricture, Follow-Up Studies
Abstract

International audience; BACKGROUND AND AIMS: The natural history of perianal Crohn’s disease (PCD) remains poorly described and is mainly based on retrospective studies from referral centres. The aim of this study was to assess the incidence, outcomes and predictors of the onset of PCD. METHODS: All incident cases of patients diagnosed with possible CD were prospectively registered from 1994 to 1997 in Brittany, a limited area in France. At diagnosis, the clinical features of perianal disease were recorded. All patient charts were reviewed from the diagnosis to the last clinic visit in 2015. RESULTS: Among the 272 out of 331 incident CD patients followed up, 51 (18.7%) patients had PCD at diagnosis. After a mean follow-up of 12.8 years, 93 (34%) patients developed PCD. The cumulative probabilities of perianal CD occurrence were 22%, 29%, and 32% after 1 year, 5 years, and 10 years, respectively. The cumulative probabilities of anal ulceration were 14%, and 19% after 1 year and 10 years, respectively. Extraintestinal manifestations were associated with the occurrence of anal ulceration. The cumulative probabilities of fistulizing PCD were 11%, 16%, and 19% after 1 year, 5 years, and 10 years, respectively. Extraintestinal manifestations, rectal involvement and anal ulceration were predictors of fistulizing PCD. The cumulative probability of developing anal stricture was 4% after 10 years. CONCLUSIONS: PCD is frequently observed during CD, in approximately one-third of patients. These data underline the need for targeted therapeutic research on primary perianal lesions (proctitis, anal ulceration) to avoid the onset of fistulizing perianal disease.

Published
2022

45. Surgical data science – from concepts toward clinical translation

Author

Hubertus Feussner, Swaroop Vedula, Ozanan R. Meireles, Nicolas Padoy, Carla M. Pugh, Russell H. Taylor, Duygu Sarikaya, Bernard Gibaud, Jan Goedeke, Pietro Mascagni, Pierre Jannin, Hirenkumar Nakawala, Toby Collins, Beat P. Müller-Stich, Teodor P. Grantcharov, Stamatia Giannarou, Ines Gockel, Gregory D. Hager, Dogu Teber, Doreen Heckmann-Nötzel, Justin W. Collins, Matthias Eisenmann, Lena Maier-Hein, Sinan Onogur, Anand Malpani, Frank Ückert, Hani J. Marcus, Germain Forestier, Luc Joyeux, Daniel R. Leff, Keno März, Daniel A. Hashimoto, Johannes Fallert, Thomas Neumuth, Minu D. Tizabi, Tobias Roß, Makoto Hashizume, Lars Mündermann, Kevin Cleary, Raphael Sznitman, Kyle Lam, Nassir Navab, Alexander Seitel, Martin Wagner, Amin Madani, Stefanie Speidel, Ron Kikinis, Adrian Park, Danail Stoyanov, Gabor Fichtinger, Hannes Kenngott, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, Gazi University, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), Johns Hopkins University (JHU), La société Karl STORZ, Technische Universität München = Technical University of Munich (TUM), Imperial College London, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Università degli studi di Verona = University of Verona (UNIVR), Johns Hopkins University School of Medicine [Baltimore], Stanford University School of Medicine [CA, USA], University College of London [London] (UCL), Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington DC, Queen's University [Kingston, Canada], Institut de Recherche en Informatique Mathématiques Automatique Signal - IRIMAS - UR 7499 (IRIMAS), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Monash university, University of Toronto, Kyushu University, Heidelberg University Hospital [Heidelberg], Harvard Medical School [Boston] (HMS), University of Bern, Universität Leipzig, University Hospital Leipzig, Ludwig-Maximilians-Universität München (LMU), Massachusetts General Hospital [Boston], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Baylor College of Medicine (BCM), Baylor University, University Health Network, UCL Institute of Neurology, Queen Square [London], Universität Karlsruhe (TH), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), This work was supported by the European Research Council (ERC) starting grant COMBIOSCOPY under the New Horizon Framework Programme grant agreement [ERC-2015-StG-637960], the Helmholtz Imaging Platform (HIP), a platform of the Helmholtz Incubator on Information and Data Science, the NCT Heidelberg, BPI France (project CONDOR), the Johns Hopkins Science of Learning Institute Research Grant, the National Institutes of Health [NIDCR R01 DE025265, P41 EB015902, P41 EB015898, R01 CA235589], the Surgical Oncology Program of the National Center for Tumor Diseases (NCT) Heidelberg, KARL STORZ SE & Co. KG, the Royal Society (UF140290) and NIHR Imperial BRC (Biomedical Research Centre), the ERC - H2020 Autonomous Robotic Surgery (ARS) grant agreement [ERC-2016-ADG-742671], the Surgical Metrics Project - American College of Surgeons (National Society Contract), the Quantified Physician - 7-SIGMA Simulation Systems, Minnesota, MN (Industry Contract), the Tourniquet Master Training - DOD SBIR Phase IIb - Continuation Award [W81XWH-13-C-0021], the Ontology for Human Motion and Psychomotor Performance - Stanford University Media-X, Motion Analysis for Microvascular Anastomosis - University of Wisconsin (Academic Contract), the Precision Learning Initiative - American Medical Association (National Society Grant), Quantifying the Metrics of Surgical Mastery: An Exploration in Data Science (NIH) [R01DK123445], the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) [203145Z/16/Z], Engineering and Physical Sciences Research Council (EPSRC) [EP/P027938/1, EP/R004080/1, EP/P012841/1], the Royal Academy of Engineering Chair in Emerging Technologies, the St. Michael’s Hospital, the University of Toronto, the Grant-in-Aid for Scientific Research on Innovative Area from MEXT, Japan, the National Cancer Data Ecosystem, contract number 19X037Q under Task Order HHSN26100071 from NCI, the project ProteCT [BMBF 16SV8568], the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) as part of Germany’s Excellence Strategy - EXC 2050/1 - Project ID 390696704 - Cluster of Excellence 'Centre for Tactile Internet with Human-in-the-Loop' (CeTI), the Canada Research Chair in Computer Integrated Surgery, Natural Sciences and Engineering Research Council of Canada, the ANR with grants ANR-16-CE33-0009 (project DeepSurg), ANR-10-IAHU-02 (IHU Strasbourg) and ANR-20-CHIA-0029-01 (Chair AI4ORSafety), and the Federal Ministry of Economics and Energy (BMWi) and the German Aerospace Center (DLR) within the OP 4.1 project [BMWI 01MT17001C]., ANR-16-CE33-0009,DeepSurg,Apprentissage Profond à partir de Vidéos Chirurgicales Multi-vues et Multimodales pour Faciliter la Gestion du Bloc Opératoire(2016), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), ANR-20-CHIA-0029,AI4ORSafety,Evaluation automatique des vues endoscopiques pour la validation des points de contrôle au bloc opératoire(2020), European Project: 637960,H2020,ERC-2014-STG,COMBIOSCOPY(2015), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Kyushu University [Fukuoka], Universität Leipzig [Leipzig], Institute of Neurology - UCL/Queen Square [London, UK] (IN-UCL-QS), 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), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne] (NCT / DKFZ), and Technische Universität Dresden = Dresden University of Technology (TU Dresden)

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial intelligence, Surgical data science, Computer science, Computer Vision and Pattern Recognition (cs.CV), media_common.quotation_subject, Aucun, Delphi method, Computer Science - Computer Vision and Pattern Recognition, Health Informatics, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Field (computer science), Machine Learning (cs.LG), [SPI.AUTO]Engineering Sciences [physics]/Automatic, Machine Learning, 03 medical and health sciences, Computer Science - Computers and Society, 0302 clinical medicine, Computers and Society (cs.CY), Health care, FOS: Electrical engineering, electronic engineering, information engineering, Humans, Radiology, Nuclear Medicine and imaging, Quality (business), 030304 developmental biology, media_common, 0303 health sciences, Radiological and Ultrasound Technology, business.industry, Clinical translation, Image and Video Processing (eess.IV), Data Science, Deep learning, Electrical Engineering and Systems Science - Image and Video Processing, Computer aided surgery, Computer Graphics and Computer-Aided Design, Data science, 3. Good health, Current practice, 030220 oncology & carcinogenesis, Data analysis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Computer Vision and Pattern Recognition, business, Data Annotation
Abstract

Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.

Published
2022

46. Multimodality imaging approach to left ventricular dysfunction in diabetes

Author

Gianluca Pontone, Magnus Bäck, Pál Maurovich-Horvat, Geneviève Derumeaux, Phillippe Charron, Stefan Neubauer, Erwan Donal, Patrizio Lancellotti, Bernard Cosyns, Eylem Levelt, Antti Saraste, Bogdan A. Popescu, Julien Magne, Thomas H. Marwick, Danilo Neglia, Jeroen J. Bax, Ivan Stankovic, Victoria Delgado, Marc R. Dweck, Sven Plein, Maurizio Galderisi, Philippe Bertrand, Niall G Keenan, Thor Edvardsen, Alessia Gimelli, Clinical sciences, Cardio-vascular diseases, Cardiology, Jonchère, Laurent, Baker Heart and Diabetes Institute (AUSTRALIA), Fondazione Toscana Gabriele Monasterio, University of Leeds, Leiden University, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Leiden University Medical Center (LUMC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Leicester, Semmelweis University of Medicine [Budapest], University of Oxford, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Turku, Universitair Ziekenhuis Brussel = University Hospital of Brussels (UZ Brussel), Oslo University Hospital [Oslo], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Bari Aldo Moro (UNIBA), University of Oxford [Oxford], Universitair Ziekenhus Brussel (UZ Brussel), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Universiteit Leiden, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
medicine.medical_specialty, Consensus, Endocrinology, Diabetes and Metabolism, Diastole, heart failure, 030204 cardiovascular system & hematology, MECHANISMS, Pathogenesis, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrosis, Internal medicine, Diabetic cardiomyopathy, Diabetes mellitus, Diabetes Mellitus, medicine, diabetic cardiomyopathy, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Subclinical infection, Cardioprotection, [SDV.IB] Life Sciences [q-bio]/Bioengineering, diabetes, business.industry, Microcirculation, General Medicine, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, Cardiology, Screening, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, Cardiology and Cardiovascular Medicine
Abstract

Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment.

Published
2022

47. Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON-HF trial

Author

Cecilia Linde, Gianluigi Savarese, Camilla Hage, Emmanuel Oger, Lars H. Lund, Erwan Donal, Ashwin Venkateshvaran, Anna Lundberg, Lina Benson, Jean-Claude Daubert, Karolinska Institute, Karolinska University Hospital [Stockholm], Novartis Pharmaceutical Corporation, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Federation Francaise de Cardiologie/Societe Francaise de Cardiologie, France, Medtronic Bakken Research Center, Maastricht, the Netherlands MedtronicNetherlands Government, Novartis Novartis, Swedish Research Council (Vetenskapsrade) Swedish Research Council [20180899], Jonchère, Laurent, 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), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, Ventricular Function, Left, Sacubitril, 0302 clinical medicine, Left atrial enlargement, Heart failure with borderline ejection fraction, Medicine, 030212 general & internal medicine, Structural heart disease, Aged, 80 and over, Eligibility, Clinical Trials as Topic, Ejection fraction, Aminobutyrates, Heart failure with mid-range ejection fraction, 3. Good health, Heart failure with preserved ejection fraction, Valsartan, Echocardiography, Cardiology, cardiovascular system, Female, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, circulatory and respiratory physiology, medicine.drug, Heart failure with mildly reduced ejection fraction, Trial design, medicine.medical_specialty, PARAGON‐HF, Angiotensin Receptor Antagonists, 03 medical and health sciences, Internal medicine, Humans, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Sacubitril/valsartan, Aged, Heart Failure, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Biphenyl Compounds, PARAGON-HF, Stroke Volume, Original Articles, Heart failure with mid‐range ejection fraction, medicine.disease, RC666-701, Heart failure, business, Sacubitril, Valsartan
Abstract

International audience; Aims In the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON-HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios. Methods and results Eligibility was assessed in the Karolinska-Rennes study (acute HFpEF, LVEF >= 45%, and N-terminal pro-B-type natriuretic peptide >= 300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (= 45%) with N-terminal pro-B-type natriuretic peptide and cardiac structure/function assessed, eligibility for sacubitril/valsartan was according to PARAGON-HF complete criteria 34%, pragmatic criteria 63%, LVEF below lower limit of normal range 5.4%, and LVEF below mean of normal range 41%. Cardiac structural impairment was almost ubiquitous. Ineligibility was more due to exclusion criteria than failing to meet inclusion criteria.

Published
2022

48. Molecular networking for drug toxicities studies: The case of hydroxychloroquine in covid-19 patients

Author

Pierre-Jean Ferron, Brendan Le Daré, Julie Bronsard, Clara Steichen, Elodie Babina, Romain Pelletier, Thierry Hauet, Isabelle Morel, Karin Tarte, Florian Reizine, Bruno Clément, Bernard Fromenty, Thomas Gicquel, Centre Hospitalier Universitaire [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), CHU Pontchaillou [Rennes], Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale, Inserm, Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM, HAL UR1, Admin, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biology (General), Correlation of Data, Spectroscopy, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Fatty Acids, General Medicine, Middle Aged, 3. Good health, Computer Science Applications, Chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Chemical and Drug Induced Liver Injury, HepaRG, Metabolic Networks and Pathways, Hydroxychloroquine, Drug-Related Side Effects and Adverse Reactions, QH301-705.5, Cell Survival, Antiviral Agents, Catalysis, Article, Cell Line, Inorganic Chemistry, 03 medical and health sciences, Fatty liver, Humans, Obesity, Physical and Theoretical Chemistry, Molecular networking, QD1-999, Molecular Biology, 030304 developmental biology, Aged, Drug metabolism, Organic Chemistry, COVID-19, COVID-19 Drug Treatment, Linear Models, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, molecular networking, hydroxychloroquine, drug metabolism, fatty liver
Abstract

International audience; Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2022

49. Histoire de la kétamine : une molécule ancienne qui a toujours la cote

Author

Daré, Brendan Le, Pelletier, Romain, Morel, Isabelle, Gicquel, Thomas, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), None, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Anesthetics, Dissociative, ketamine, Substance-Related Disorders, recreational use, [SDV]Life Sciences [q-bio], Stereoisomerism, analgesia, History, 20th Century, anesthesia, History, 21st Century, analgésie, anesthésie, kétamine, dépression, usage récréatif, depression, Humans
Abstract

National audience; The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with psychodysleptic, hallucinogenic and dissociative properties. Following the first administration of ketamine to humans in 1964 in Jackson prison (Michigan, USA), its dissociative effects associated with short anaesthesia were reported, and a patent for its human use was filed in 1966. In the 1990s, the discovery of opioid-induced hyperalgesia sparked interest in ketamine as an analgesic. In recent years, the human use of ketamine, and in particular its esketamine enantiomer, has shifted towards the treatment of depression. The first cases of ketamine abuse were reported in 1992 in France, leading to special surveillance by the health authorities, and its inclusion in the list of narcotic drugs in 1997. Today, ketamine has become an attractive substance for recreational use, gradually emerging from alternative techno circles to spread to more commercial party scenes. These elements represent a public health concern, associated with the risk of developing new chemically synthesized analogues, the harmful effects of which are still little known.

Published
2022

50. To be malnourished or not to be malnourished: that is the question!

Author

Ronan Thibault, Mallorie Kerjouan, Jouneau Stéphane, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), and Jonchère, Laurent

Subjects
[SDV] Life Sciences [q-bio], Pulmonary and Respiratory Medicine, 03 medical and health sciences, Pediatrics, medicine.medical_specialty, 0302 clinical medicine, 030228 respiratory system, business.industry, [SDV]Life Sciences [q-bio], Medicine, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022

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