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61 results on '"Hospices Civils de Lyon (HCL)"'

1. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles

Author

Bettina Fabiani, Sylvain Mareschal, Pascaline Etancelin, Tony Petrella, Fabrice Jardin, Bruno Tesson, Sydney Dubois, Jean-Philippe Jais, Christiane Copie-Bergman, Gilles Salles, Elodie Bohers, Corinne Haioun, Pierre-Julien Viailly, Thierry Jo Molina, Philippe Ruminy, Karen Leroy, Hervé Tilly, Pauline Peyrouze, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot CALYM [Pierre-Benite], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Lille 2 - Faculté de Médecine, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de pathologie, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département d'Hématologie, Institut Carnot Lymphome (CALYM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre de pathologie [Dijon]

Subjects
0301 basic medicine, Male, Research paper, Key genes, Transcriptomic variability, DNA Copy Number Variations, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Locus (genetics), Computational biology, Independent component analysis, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hemic and lymphatic diseases, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Copy-number variation, Gene signatures, prognosis, Genetic Association Studies, lcsh:R5-920, Gene Expression Profiling, lcsh:R, Gene signatures, Chromosome Mapping, Computational Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Molecular Sequence Annotation, General Medicine, Diffuse large B-cell lymphoma, Gene signature, medicine.disease, Immunohistochemistry, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, Affymetrix genechip, Female, prognosis, Lymphoma, Large B-Cell, Diffuse, lcsh:Medicine (General)
Abstract

Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis

Published
2019

2. Epigenetics in atrial fibrillation: A reappraisal

Author

Rishi Arora, Philippe Chevalier, H. Llewelyn Roderick, Babken Asatryan, Sophie Rome, Rosa Doñate Puertas, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Northwestern University Feinberg School of Medicine, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bern University Hospital [Berne] (Inselspital), University of Oslo (UiO), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), and CarMeN, laboratoire

Subjects
Epigenomics, Epidrug, Systems biology, [SDV]Life Sciences [q-bio], Context (language use), Personalized therapy, 030204 cardiovascular system & hematology, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Humans, Heart Atria, 030212 general & internal medicine, Epigenetics, business.industry, Cardiac arrhythmia, Epigenetic, Atrial fibrillation, Atrial Remodeling, Epigenome, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], DNA methylation, Cardiology and Cardiovascular Medicine, business
Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important cause of morbidity and mortality globally. Atrial remodeling includes changes in ion channel expression and function, structural alterations, and neural remodeling, which create an arrhythmogenic milieu resulting in AF initiation and maintenance. Current therapeutic strategies for AF involving ablation and antiarrhythmic drugs are associated with relatively high recurrence and proarrhythmic side effects, respectively. Over the last 2 decades, in an effort to overcome these issues research has sought to identify the genetic basis for ,AF thereby gaining insight into the regulatory mechanisms governing its pathophysiology. Despite identification of multiple gene loci associated with AF, thus far none has led to a therapy, indicating additional contributors to pathology. Recently, in the context of expanding knowledge of the epigenome (DNA methylation, histone modifications, and noncoding RNAs), its potential involvement in the onset and progression of AF pathophysiology has started to emerge. Probing the role of various epigenetic mechanisms that contribute to AF may improve our knowledge of this complex disease, identify potential therapeutic targets, and facilitate targeted therapies. Here, we provide a comprehensive review of growing epigenetic features involved in AF pathogenesis and summarize the emerging epigenomic targets for therapy that have been explored in preclinical models of AF. ispartof: Heart Rhythm vol:18 issue:5 pages:824-832 ispartof: location:United States status: Published online

Published
2021

3. Cortical bone viscoelastic damping assessed with resonant ultrasound spectroscopy reflects porosity and mineral content

Author

Quentin Grimal, Xiran Cai, Fan Fan, Hélène Follet, Pascal Laugier, Françoise Peyrin, Haijun Niu, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Beihang University (BUAA), ShanghaiTech University [Shanghai], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), grimal, quentin, Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Materials science, Bone disease, Cortical bone, Biomedical Engineering, 02 engineering and technology, Matrix (biology), Mineral content, Damping, Bone and Bones, Viscoelasticity, Biomaterials, 03 medical and health sciences, Crystallinity, 0302 clinical medicine, Bone Density, medicine, Humans, Composite material, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Porosity, Aged, Resonant ultrasound spectroscopy, Minerals, Spectrum Analysis, [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], 030206 dentistry, 021001 nanoscience & nanotechnology, medicine.disease, Quality factor, Shear (sheet metal), medicine.anatomical_structure, Mechanics of Materials, 0210 nano-technology
Abstract

Viscoelasticity is an essential property of bone related to fragility, which is altered in aging and bone disease. Bone viscoelastic behavior is attributed to several mechanisms involving collagen and mineral properties, porosities, and bone hierarchical tissue organization. We aimed to assess the relationships between cortical bone viscoelastic damping measured with Resonant Ultrasound Spectroscopy (RUS), microstructural and compositional characteristics. We measured 52 bone specimens from the femur of 26 elderly human donors. RUS provided a shear damping coefficient at a frequency of the order of 150 kHz. The characteristics of the structure of the vascular pore network and tissue mineral density were measured using synchrotron radiation high-resolution computed tomography (SR- μ CT). Fourier transformed infrared microspectroscopy (FTIRM) was used to quantify mineral-to-organic phase ratio, mineral maturity, crystallinity, and collagen maturity. Cross-links were quantified from biochemistry. Viscoelastic damping was found to increase with vascular porosity ( r = 0 . 68 ), to decrease with the degree of mineralization of the extravascular matrix ( r = − 0 . 68 ), and was marginally affected by collagen. We built a multilinear model suggesting that when porosity is controlled, the variation of mineral content explains a small additional part of the variability of damping. The work supports the consideration of viscoelasticity measurement as a potential biomarker of fragility and provides a documentation of bone viscoelastic behavior and its determinants in a frequency range rarely investigated.

Published
2021

4. PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL

Author

Vahid Asnafi, Mathieu Simonin, Guillaume Charbonnier, Carlos Graux, Guillaume P. Andrieu, Philippe Rousselot, Françoise Huguet, Charlotte L. Smith, Milena Kohn, Agata Cieslak, Véronique Lhéritier, Salvatore Spicuglia, Marie-Emilie Dourthe, Nicolas Boissel, Hervé Dombret, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Spinelli, Lionel, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Coordination du Groupe GRAALL [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier de Versailles André Mignot (CHV), and 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)

Subjects
Male, BLOOD COMMENTARY, [SDV]Life Sciences [q-bio], Mice, SCID, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Epigenesis, Genetic, Histones, 0302 clinical medicine, Loss of Function Mutation, Tumor Cells, Cultured, Medicine, 0303 health sciences, Lymphoid Neoplasia, biology, Gene Expression Regulation, Leukemic, Polycomb Repressive Complex 2, JAK-STAT signaling pathway, Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Stem cell, PRC2, Adult, Adolescent, Antineoplastic Agents, Hormonal, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Epigenetics, Interleukin-7 receptor, Loss function, 030304 developmental biology, business.industry, Cell Biology, Minimal residual disease, Bromodomain, biology.protein, Cancer research, Prednisone, business, Transcription Factors
Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a group of aggressive hematological cancers with dismal outcomes that are in need of new therapeutic options. Polycomb repressor complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL, yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients. We found that PRC2 genetic lesions are frequent events in T-ALL and are not restricted to early thymic precursor ALL. PRC2 loss of function associates with activating mutations of the IL7R/JAK/STAT pathway. PRC2-altered T-ALL patients respond poorly to prednisone and have low bone marrow blast clearance and persistent minimal residual disease. Furthermore, we identified that PRC2 loss of function profoundly reshapes the genetic and epigenetic landscapes, leading to the reactivation of stem cell programs that cooperate with bromodomain and extraterminal (BET) proteins to sustain T-ALL. This study identifies BET proteins as key mediators of the PRC2 loss of function-induced remodeling. Our data have uncovered a targetable vulnerability to BET inhibition that can be exploited to treat PRC2-altered T-ALL patients.

Published
2021

5. Impact of the reperfusion status for predicting the final stroke infarct using deep learning

Author

Debs, Noëlie, Cho, Tae-Hee, Rousseau, David, Berthezène, Yves, Buisson, Marielle, Eker, Omer, Mechtouff, Laura, Nighoghossian, Norbert, Ovize, Michel, Frindel, Carole, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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), Hospices Civils de Lyon, Departement de Neurologie (HCL), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Service de Radiologie et IRM, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-16-RHUS-0009,MARVELOUS,MARVELOUS(2016), ANR-18-RHUS-0001,BOOSTER,Brain clOt persOnalized therapeutic Strategies for sTroke Emergent Reperfusion(2018), CCSD, Accord Elsevier, MARVELOUS - - MARVELOUS2016 - ANR-16-RHUS-0009 - RHUS - VALID, Brain clOt persOnalized therapeutic Strategies for sTroke Emergent Reperfusion - - BOOSTER2018 - ANR-18-RHUS-0001 - RHUS - VALID, 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, Reperfusion status, Regular Article, Convolutional neural network, lcsh:Computer applications to medicine. Medical informatics, lcsh:RC346-429, Brain Ischemia, Stroke, Deep Learning, Diffusion Magnetic Resonance Imaging, Magnetic resonance imaging, [INFO.EIAH] Computer Science [cs]/Technology for Human Learning, Infarction, Reperfusion, Humans, lcsh:R858-859.7, [INFO.EIAH]Computer Science [cs]/Technology for Human Learning, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prediction, lcsh:Neurology. Diseases of the nervous system, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

Graphical abstract, Highlights • Deep learning predictive models of the final stroke infarct may have better performances when trained on reperfusion status specific subsets. • The proposed predictive models outperformed the standards threshold-based perfusion-diffusion mismatch models. • Comparing the predicted infarct in case of a successful vs failed reperfusion may help in estimating the treatment effect and guiding therapeutic decisions in selected patients., Background Predictive maps of the final infarct may help therapeutic decisions in acute ischemic stroke patients. Our objectives were to assess whether integrating the reperfusion status into deep learning models would improve their performance, and to compare them to current clinical prediction methods. Methods We trained and tested convolutional neural networks (CNNs) to predict the final infarct in acute ischemic stroke patients treated by thrombectomy in our center. When training the CNNs, non-reperfused patients from a non-thrombectomized cohort were added to the training set to increase the size of this group. Baseline diffusion and perfusion-weighted magnetic resonance imaging (MRI) were used as inputs, and the lesion segmented on day-6 MRI served as the ground truth for the final infarct. The cohort was dichotomized into two subsets, reperfused and non-reperfused patients, from which reperfusion status specific CNNs were developed and compared to one another, and to the clinically-used perfusion-diffusion mismatch model. Evaluation metrics included the Dice similarity coefficient (DSC), precision, recall, volumetric similarity, Hausdorff distance and area-under-the-curve (AUC). Results We analyzed 109 patients, including 35 without reperfusion. The highest DSC were achieved in both reperfused and non-reperfused patients (DSC = 0.44 ± 0.25 and 0.47 ± 0.17, respectively) when using the corresponding reperfusion status-specific CNN. CNN-based models achieved higher DSC and AUC values compared to those of perfusion-diffusion mismatch models (reperfused patients: AUC = 0.87 ± 0.13 vs 0.79 ± 0.17, P

Published
2021

6. Proposed Requirements for Cardiovascular Imaging Related Machine Learning Evaluation (PRIME) Checklist

Author

Joel T. Dudley, Geoffrey H. Tison, Sirish Shrestha, Naveena Yanamala, Mahdi Tabassian, Lasse Lovstakken, Marco Piccirilli, Partho P. Sengupta, Olivier Bernard, Emmanuel Messas, Nicolas Duchateau, Rima Arnaout, Jens-Uwe Voigt, Mathieu Pernot, Khader Shameer, Kipp W. Johnson, James K. Min, B. Berthon, Johan W. Verjans, Nobuyuki Kagiyama, Erwan Donal, Rahul C. Deo, Piotr J. Slomka, Jan D'hooge, Modeling & analysis for medical imaging and Diagnosis (MYRIAD), 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, DEEP, PREDICTION, digital health, 030204 cardiovascular system & hematology, Machine learning, computer.software_genre, reproducible research, reporting guidelines, 030218 nuclear medicine & medical imaging, Domain (software engineering), 03 medical and health sciences, 0302 clinical medicine, MICROARRAY, Multidisciplinary approach, Internal medicine, Health care, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Radiology, Nuclear Medicine and imaging, cardiovascular imaging, ComputingMilieux_MISCELLANEOUS, Pace, Flexibility (engineering), Science & Technology, business.industry, ARTIFICIAL-INTELLIGENCE, Radiology, Nuclear Medicine & Medical Imaging, Foundation (evidence), artificial intelligence, Digital health, Checklist, machine learning, Cardiology, Cardiovascular System & Cardiology, Artificial intelligence, Cardiology and Cardiovascular Medicine, business, computer, Life Sciences & Biomedicine, checklist
Abstract

Machine learning (ML) has been increasingly used within cardiology, particularly in the domain of cardiovascular imaging. Due to the inherent complexity and flexibility of ML algorithms, inconsistencies in the model performance and interpretation may occur. Several review articles have been recently published that introduce the fundamental principles and clinical application of ML for cardiologists. This paper builds on these introductory principles and outlines a more comprehensive list of crucial responsibilities that need to be completed when developing ML models. This paper aims to serve as a scientific foundation to aid investigators, data scientists, authors, editors, and reviewers involved in machine learning research with the intent of uniform reporting of ML investigations. An independent multidisciplinary panel of ML experts, clinicians, and statisticians worked together to review the theoretical rationale underlying 7 sets of requirements that may reduce algorithmic errors and biases. Finally, the paper summarizes a list of reporting items as an itemized checklist that highlights steps for ensuring correct application of ML models and the consistent reporting of model specifications and results. It is expected that the rapid pace of research and development and the increased availability of real-world evidence may require periodic updates to the checklist. ispartof: Jacc-Cardiovascular Imaging vol:13 issue:9 pages:2017-2035 ispartof: location:United States status: published

Published
2020

7. Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study

Author

Mariola Pęczkowska, Akihiro Sukurai, Anita Špehar Uroić, Andreas Machens, Laura Fugazzola, Tushar Bandgar, Carla Vaz Ferreira Vargas, Hartmut P. H. Neumann, Martin Schlumberger, Delphine Drui, Patricia Fainstein-Day, Francoise Borson Chazot, Amandine Berdelou, Tom R. Kurzawinski, Delphine Mirebeau-Prunier, Olivier Chabre, Dominique Maiter, Philippe Caron, Gabriella Sanso, Tsuneo Imai, Camilo Jimenez, Frederic Sebag, Márta Korbonits, Atila Patocs, Laura Valerio, Sarka Dvorakova, Claudio Letizia, Srivandana Akshintala, Christian Godballe, Regis Cohen, Eric Baudin, Caterina Mian, Jolanta Krajewska, Rossella Elisei, Laurence Leclerc, Tobias Else, Marc Klein, Kornelia Hasse-Lazar, Thierry Brue, Steven G. Waguespack, Petr Vlcek, Nuria Valdes, Thera P. Links, Ana Luisa Maia, Ana O. Hoff, Henning Dralle, Frederic Castinetti, André Lacroix, Xiao Ping Qi, Maria João Bugalho, Maralyn Druce, Nelson Wohllk, Barbara Jarzab, Birke Bausch, Delmar M. Lourenço, John Glod, Shinya Uchino, Caroline Brain, Letizia Canu, Charis Eng, Marta Barontini, Jes Sloth Mathiesen, Antoine Tabarin, Elizabeth G. Grubbs, Lucieli Ceolin, Sandrine Laboureau, Repositório da Universidade de Lisboa, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), University of Coimbra [Portugal] (UC), Endocrine Section, Hospital del Salvador, Département d'Endocrinologie [CHU Nantes] (Institut du Thorax), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut du Thorax [Nantes], Queen Mary University of London (QMUL), Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Department of Internal Medicine and Medical Specialties, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Endocrinology and Diabetes Mellitus, Hôpital Delafontaine, CHU Bordeaux [Bordeaux], Endocrinology, Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Department of Medical and Surgical Sciences, Universita degli Studi di Padova, Department of Hypertension, Institute of Cardiology, Service de chirurgie générale et endocrinienne, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Aix Marseille Université (AMU), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Centro de Investigaciones Endocrinológicas, Hospital de Niños R. Gutiérrez, Genomic Medicine Institute, Cleveland Clinic, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Fédération d'endocrinologie, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Padova = University of Padua (Unipd), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, Pediatrics, PHEOCHROMOCYTOMA, MEDULLARY-THYROID CARCINOMA, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Adrenal Gland Neoplasms, Multiple Endocrine Neoplasia Type 2b, Internal Medicine, Endocrinology, surgery, 0302 clinical medicine, DOMAIN, 030212 general & internal medicine, Child, MUTATION, men2, Middle Aged, Prognosis, Penetrance, CANCER, 3. Good health, Diabetes and Metabolism, Natural history, Survival Rate, Child, Preschool, RET PROTOONCOGENE, MANAGEMENT, Cohort, Thyroidectomy, Female, Multiple endocrine neoplasia type 2b, Adult, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, Pheochromocytoma, 03 medical and health sciences, Young Adult, medicine, Humans, Thyroid Neoplasms, Survival rate, Retrospective Studies, adrenal gland, business.industry, Infant, International Agencies, Retrospective cohort study, medicine.disease, Carcinoma, Neuroendocrine, MEN2b, business, Follow-Up Studies
Abstract

© 2019 Elsevier Ltd. All rights reserved., Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. Methods: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. Findings: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range

Published
2019

8. Concepts and procedures for mapping food and health research infrastructure: New insights from the EuroDISH project

Author

Léopold Fezeu, Rosalie A. M. Dhonukshe-Rutten, Pieter van 't Veer, Marga C. Ocké, Kerry Brown, Paul Finglas, Lada Timotijevic, Nadia Slimani, Inge Tetens, K.L. Zimmermann, H.M. Snoek, Marjolein Geurts, Cécile Vors, Martine Laville, Giuditta Perozzi, Krijn J. Poppe, Johanne Louise Arentoft, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
0301 basic medicine, Engineering, medicine.medical_specialty, Knowledge management, [SDV]Life Sciences [q-bio], Determinants of dietary intake, Boundary (real estate), 03 medical and health sciences, 0302 clinical medicine, Research community, Research environment, medicine, Consument & Keten, 030212 general & internal medicine, Sensory Science and Eating Behaviour, Pace, VLAG, Human Nutrition & Health, 030109 nutrition & dietetics, Scope (project management), business.industry, Programmamanagement, Public health, Environmental resource management, Humane Voeding & Gezondheid, Research infrastructure, Determinants of dietary, Onderwijsinstituut, EuroDISH, Food and health, Europe, Sensoriek en eetgedrag, Disease risk, business, Consumer and Chain, intake, Food Science, Biotechnology
Abstract

International audience; Background: Recent initiatives in Europe have encouraged the formalisation of research infrastructure to unify fragmented facilities, resources and services; and to facilitate world-class research of complex public health challenges, such as those related to non-communicable disease. How this can be achieved in the area of food and health has, to date, been unclear. Scope and approach: This commentary paper presents examples of the types of food and health research facilities, resources and services available in Europe. Insights are provided on the challenge of identifying and classifying research infrastructure. In addition, suggestions are made for the future direction of food and health research infrastructure in Europe. These views are informed by the EuroDISH project, which mapped research infrastructure in four areas of food and health research: Determinants of dietary behaviour; Intake of foods/nutrients; Status and functional markers of nutritional health; Health and disease risk of foods/nutrients. Key findings and conclusion: There is no objective measure to identify or classify research infrastructure. It is therefore, difficult to operationalise this term. EuroDISH demonstrated specific challenges with identifying the degree an organisation, project, network or national infrastructure could be considered a research infrastructure; and establishing the boundary of a research infrastructure (integral hard or soft facilities/resources/services). Nevertheless, there are opportunities to create dedicated food and health research infrastructures in Europe. These would need to be flexible and adaptable to keep pace with an ever-changing research environment and bring together the multi-disciplinary needs of the food and health research community. (C) 2017 Elsevier Ltd. All rights reserved.

Published
2017

9. Continuum of vasodilator stress from rest to contrast medium to adenosine hyperemia for fractional flow reserve assessment

Author

Keith G. Oldroyd, Sérgio Bravo Baptista, Nico H.J. Pijls, Frederik M. Zimmermann, Barry Hennigan, Gilles Rioufol, Hyoung-Mo Yang, Julien Adjedj, Mitsuaki Matsumura, Bon-Kwon Koo, Seung-Jung Park, Emanuele Barbato, Giovanni Esposito, Nils P. Johnson, Akiko Maehara, Antonio Maria Leone, William F. Fearon, Richard L. Kirkeeide, Bruno Trimarco, Nils Witt, Bernard De Bruyne, Colin Berry, Allen Jeremias, K. Lance Gould, George S. Chrysant, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Cardiovascular Biomechanics, Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Johnson, Nils P, Jeremias, Allen, Zimmermann, Frederik M, Adjedj, Julien, Witt, Nil, Hennigan, Barry, Koo, Bon Kwon, Maehara, Akiko, Matsumura, Mitsuaki, Barbato, Emanuele, Esposito, Giovanni, Trimarco, Bruno, Rioufol, Gille, Park, Seung Jung, Yang, Hyoung Mo, Baptista, Sérgio B, Chrysant, George S, Leone, Antonio M, Berry, Colin, De Bruyne, Bernard, Gould, K. Lance, Kirkeeide, Richard L, Oldroyd, Keith G, Pijls, Nico H. J, and Fearon, William F.

Subjects
Male, Cardiac Catheterization, Time Factors, medicine.medical_treatment, Vasodilator Agents, [SDV]Life Sciences [q-bio], Contrast Media, Fractional flow reserve, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, 030212 general & internal medicine, Prospective Studies, fractional flow reserve, Cardiac catheterization, Vasodilators, Middle Aged, Coronary Vessels, 3. Good health, Fractional Flow Reserve, Myocardial, Cateterização cardíaca, Injections, Intra-Arterial, adenosine, Area Under Curve, Injections, Intravenous, Cardiology, Aortic pressure, Vasodilatadores, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Revascularization, 03 medical and health sciences, contrast medium, Predictive Value of Tests, Internal medicine, medicine, Humans, Arterial Pressure, Instantaneous wave-free ratio, Aged, business.industry, Reproducibility of Results, medicine.disease, instantaneous wave-free ratio, hyperemia, Surgery, Contrast medium, Blood pressure, ROC Curve, Doença das artérias coronárias, business
Abstract

International audience; OBJECTIVES: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) \textless/=0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). BACKGROUND: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. METHODS: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. RESULTS: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 +/- 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias \textless0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR \textless/=0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p \textless 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. CONCLUSIONS: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only approximately 85% agreement.

Published
2016

10. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Author

Grégory Picard, Marie-Agnès Chauvin, Emmanuelle Loizon, Monique Estienne, Michel Lagarde, Anne Meynier, Noël Peretti, Pascale Plaisancié, Michel Guichardant, Marie-Caroline Michalski, Bérengère Benoit, Claude Genot, Manar Awada, Cyrille Debard, Christophe O. Soulage, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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-Institut National de la Recherche Agronomique (INRA), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Michalski, Marie-Caroline

Subjects
Male, MESH: Inflammation, MESH: Oxidation-Reduction, 4-hydroxy-2-alkenals, GPX2, 030309 nutrition & dietetics, métabolisme des lipides, MESH: Heat-Shock Proteins, medicine.disease_cause, Biochemistry, Intestinal absorption, MESH: Lipid Peroxidation, Lipid peroxidation, Mice, chemistry.chemical_compound, absorption digestive, Endocrinology, MESH: Fatty Acids, Omega-3, MESH: Animals, Intestinal Mucosa, Endoplasmic Reticulum Chaperone BiP, Research Articles, Heat-Shock Proteins, chemistry.chemical_classification, 0303 health sciences, MESH: Oxidative Stress, peroxydation lipidique, Glutathione peroxidase, lipid peroxidation, 3. Good health, medicine.anatomical_structure, nutrition, Alimentation et Nutrition, peroxydation des lipides, MESH: Caco-2 Cells, medicine.symptom, Oxidation-Reduction, nutrition humaine, MESH: Intestines, polyunsaturated fatty acids, medicine.medical_specialty, MESH: Intestinal Absorption, Inflammation, QD415-436, Biology, Diet, High-Fat, acide gras polyinsaturé n 3, 03 medical and health sciences, physiologie digestive, MESH: Mice, Inbred C57BL, Internal medicine, Fatty Acids, Omega-3, inflammation intestinale, medicine, Animals, Humans, Food and Nutrition, nutrition, polyunsaturated fatty acids, lipid peroxidation, 4-hydroxy-2-alkenals, intestine, MESH: Mice, intestine, 030304 developmental biology, Aldehydes, Glutathione Peroxidase, MESH: Humans, MESH: Biological Markers, Cell Biology, Small intestine, MESH: Male, Mice, Inbred C57BL, Oxidative Stress, MESH: Diet, High-Fat, Intestinal Absorption, chemistry, Paneth cell, MESH: Glutathione Peroxidase, MESH: Aldehydes, Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Oxidative stress, inflammation de l'intestin
Abstract

ISI Document Delivery No.: 004QQTimes Cited: 0Cited Reference Count: 46Cited References: Pillon Nicolas J., 2011, CHEMICAL RESEARCH IN TOXICOLOGY, V24, P752Awada, Manar Soulage, Christophe O. Meynier, Anne Debard, Cyrille Plaisancie, Pascale Benoit, Berengere Picard, Gregory Loizon, Emmanuelle Chauvin, Marie-Agnes Estienne, Monique Peretti, Noel Guichardant, Michel Lagarde, Michel Genot, Claude Michalski, Marie-CarolineFrench National Research Agency (ANR)[ANR-08-ALIA-002]; ANRThis work was supported by the French National Research Agency (ANR) Grant ANR-08-ALIA-002, AGECANINOX project.M. Awada acknowledges her PhD grant from ANR. The authors thank Lucie Ribourg and Michele Viau for their work on oil mixtures. Patricia Daira is acknowledged for her help with the 4-hydroxy-2-alkenal assay. The authors thank Jean-Michel Chardigny for useful discussions. Isabelle Jouanin (Plateforme AXIOM-MetaToul, Toulouse) is acknowledged for the synthesis of internal standards to measure 4-hydroxyl-2-alkenals in fat. Yvonne Masson is acknowledged for revising the English-language manuscript.Amer soc biochemistry molecular biology incBethesda[Awada, Manar; Plaisancie, Pascale; Estienne, Monique; Michalski, Marie-Caroline] INRA, CarMeN Lab U1235, F-69621 Villeurbanne, France. [Awada, Manar; Soulage, Christophe O.; Guichardant, Michel; Lagarde, Michel; Michalski, Marie-Caroline] Inst Natl Sci Appl, IMBL, F-69621 Villeurbanne, France. [Meynier, Anne; Genot, Claude] INRA, Biopolymeres Interact Assemblages UR1268, F-44300 Nantes, France. [Debard, Cyrille; Chauvin, Marie-Agnes] INSERM, U1060, CarMeN Lab, F-69921 Oullins, France. [Benoit, Berengere; Picard, Gregory; Loizon, Emmanuelle; Peretti, Noel; Michalski, Marie-Caroline] Univ Lyon 1, F-69622 Villeurbanne, France.marie-caroline.michalski@insa-lyon.fr; International audience; Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine.

Published
2012

11. Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading

Author

Leo Joskowicz, Moti Freiman, Karl Krissian, Jacob Sosna, Coert Metz, Noy Cohen, Ingrid Sanchez, Julien Mille, T. van Walsum, Wiro J. Niessen, Maciej Orkisz, Wilbur C.K. Wong, M. P M Q van Gils, K. Hameeteman, M. Hernández Hoyos, Gabriel P. Krestin, L. Florez Valencia, L. van den Borne, Olivier Cuisenaire, Michiel Schaap, Mehmet Akif Gulsun, P. Berman, A. van der Lugt, Philippe Douek, Maria A. Zuluaga, Huseyin Tek, M. Aissat, Fethallah Benmansour, S. Rozie, Albert C. S. Chung, Biomedical Imaging Group [Rotterdam] (BIG), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-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), Grupo IMAGINE, Universidad de los Andes [Bogota] (UNIANDES), Computer-Aided Surgery and Medical Image Processing Laboratory, The Hebrew University of Jerusalem (HUJ), MedisysResearch Lab (Medisys), Philips Research, Departamento de Ingeniería de Sistemas, Facultad de Ingeniería, Pontificia Universidad Javeriana (PUJ), Imaging and Visualization Department, Siemens Corporate Research, GIMET, Dept. de Informática y Sistemas (GIMET), University of Las Palmas de Gran Canaria (ULPGC), Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Lo Kwee-Seong Medical Image Analysis Laboratory, Hong Kong University of Science and Technology (HKUST), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), CEntre de REcherches en MAthématiques de la DEcision (CEREMADE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Department of Radiology, Hadassah Hebrew University Medical Centre, Hadassah Hebrew University, Service de Radiologie, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Imaging Science and Technology, Delft University of Technology (TU Delft), and Radiology & Nuclear Medicine

Subjects
medicine.medical_specialty, medicine.medical_treatment, Carotid arteries, Evaluation framework, Health Informatics, Information repository, computer.software_genre, Sensitivity and Specificity, Pattern Recognition, Automated, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 3d segmentation, medicine, Carotid bifurcation, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Carotid Stenosis, Radiology, Nuclear Medicine and imaging, Endarterectomy, Lumen segmentation, Carotid, Radiological and Ultrasound Technology, medicine.diagnostic_test, CTA, business.industry, Stenosis grading, Angiography, Reproducibility of Results, medicine.disease, Computer Graphics and Computer-Aided Design, Radiographic Image Enhancement, Stenosis, Carotid Arteries, Radiographic Image Interpretation, Computer-Assisted, Computer Vision and Pattern Recognition, Radiology, Data mining, Tomography, X-Ray Computed, business, computer, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithms, 030217 neurology & neurosurgery
Abstract

International audience; This paper describes an evaluation framework that allows a standardized and objective quantitative comparison of carotid artery lumen segmentation and stenosis grading algorithms. We describe the data repository comprising 56 multi-center, multi-vendor CTA datasets, their acquisition, the creation of the reference standard and the evaluation measures. This framework has been introduced at the MICCAI 2009 workshop 3D Segmentation in the Clinic: A Grand Challenge III, and we compare the results of eight teams that participated. These results show that automated segmentation of the vessel lumen is possible with a precision that is comparable to manual annotation. The framework is open for new submissions through the website http://cls2009.bigr.nl. The final accepted version of this paper is published in Medical Image Analysis, vol 15(4) ,doi:10.1016/j.media.2011.02.004

Published
2011

12. Quantification of nonlinear elasticity for the valuation of submillimeter crack length in cortical bone

Author

Sandra Guérard, Françoise Peyrin, Sylvain Haupert, Pascal Laugier, David Mitton, 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), Arts et Métiers ParisTech, LBM/Institut de Biomécanique Humaine Georges Charpak, Paris, France, parent, Université de Lyon, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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), European Synchrotron Radiation Facility (ESRF), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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)-Université Claude Bernard Lyon 1 (UCBL), 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Rayet, Béatrice

Subjects
nonlinear acoustics, Materials science, Matériaux [Sciences de l'ingénieur], [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cortical bone, Biomedical Engineering, crack, Modulus, spectroscop, synchrotron radiation micro-computed tomographyy, Models, Biological, Bone and Bones, nonlinear resonant ultrasound, Biomaterials, Nonlinear acoustics, MESH: Cortical bone, Crack, Damage, Elasticity, Nonlinear resonant ultrasound spectroscopy, Synchrotron radiation micro-computed tomography, medicine, Humans, Composite material, Elasticity (economics), Mécanique: Biomécanique [Sciences de l'ingénieur], Aged, Resonant ultrasound spectroscopy, Aged, 80 and over, Mécanique [Sciences de l'ingénieur], Mécanique: Matériaux et structures en mécanique [Sciences de l'ingénieur], Fracture mechanics, Nonlinear system, Crystallography, medicine.anatomical_structure, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Mechanics of Materials, elasticity, Tomography, Stress, Mechanical, damage
Abstract

The objective of this study was to investig ate the sensitivity of the nonlinear elastic properties of cortical bon e to the presence of a single submillime tric crac k. Nonli near elasticity was measured by nonlinear resonant ultrasound spectroscopy (NRUS) in 14 human cortical bon e specimen s. The specimen s were parallelepiped beams (50 2 2 mm3). A central notch of 500 mm was made to control crack initiation and propagation during four-point bending. The nonlinear hysteretic elastic and dissipative parameters αf and α Q, and Young's modulus Eus were measured in dry condition for undamaged (control) specimens and in dry and wet conditions for damaged specimens. The length of the crack was assessed using synchrotron radiation micro-computed tomography (SR- μCT) with a voxel size of 1.4 μm. The initial values of αf, measured on the intact specimens, were remarkably similar for all the specimens (αf ¼ 5.57 1.5). After crack propagation, the nonlinear elastic coefficient α f increased significantly (p o 0.006), with values ranging from 4.0 to –296.7. Conversely, no significant variation was observed for αQ and Eus. A more pronounced nonlinear elastic behavior was observed in hydrated specimens compared to dry specimens (p o 0.001) after propagation of a single submillimetric crack. The nonlinear elastic parameter αf was found to be significantly correlated to the crack length both in dry (R ¼0.79, p o0.01) and wet (R ¼0.84, p o0.005) conditions. Altogether these results show that nonlinear elasticity assessed by NRUS is sensitive to a single submillimetric crack induced mechanically and suggest that the humidity must be strictly controlled during measurements.

Published
2015

13. Fast automatic myocardial segmentation in 4D cine CMR datasets

Author

Pedro Morais, Denis Friboulet, João L. Vilaça, Olivier Bernard, Brecht Heyde, Sandro Queirós, Jan D'hooge, Daniel Barbosa, Universidade do Minho, Laboratory of Cardiovascular Imaging and Dynamics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), ICVS/3B's, PT Government Associate Laboratory, DIGARC, Polytechnic Institute of Cávado and Ave, 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)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Computer science, Heart Ventricles, Optical flow, Cardiac cine MRI, Magnetic Resonance Imaging, Cine, Initialization, Scale-space segmentation, Health Informatics, Fast image segmentation, Left ventricle segmentation, Sensitivity and Specificity, Imaging, Three-Dimensional, Automatic initialization, Robustness (computer science), 3d segmentation, Image Interpretation, Computer-Assisted, Humans, Radiology, Nuclear Medicine and imaging, Computer vision, Segmentation, Radiological and Ultrasound Technology, business.industry, Reproducibility of Results, Image Enhancement, Computer Graphics and Computer-Aided Design, Computer Vision and Pattern Recognition, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithms
Abstract

A novel automatic 3D+time left ventricle (LV) segmentation framework is proposed for cardiac magnetic resonance (CMR) datasets. The proposed framework consists of three conceptual blocks to delineate both endo and epicardial contours throughout the cardiac cycle: (1) an automatic 2D mid-ventricular initialization and segmentation; (2) an automatic stack initialization followed by a 3D segmentation at the end-diastolic phase; and (3) a tracking procedure. Hereto, we propose to adapt the recent B-spline Explicit Active Surfaces (BEAS) framework to the properties of CMR images by integrating dedicated energy terms. Moreover, we extend the coupled BEAS formalism towards its application in 3D MR data by adapting it to a cylindrical space suited to deal with the topology of the image data. Furthermore, a fast stack initialization method is presented for efficient initialization and to enforce consistent cylindrical topology. Finally, we make use of an anatomically constrained optical flow method for temporal tracking of the LV surface. The proposed framework has been validated on 45 CMR datasets taken from the 2009 MICCAI LV segmentation challenge. Results show the robustness, efficiency and competitiveness of the proposed method both in terms of accuracy and computational load. publisher: Elsevier articletitle: Fast automatic myocardial segmentation in 4D cine CMR datasets journaltitle: Medical Image Analysis articlelink: http://dx.doi.org/10.1016/j.media.2014.06.001 content_type: article copyright: Copyright © 2014 Elsevier B.V. All rights reserved. ispartof: MEDICAL IMAGE ANALYSIS vol:18 issue:7 pages:1115-1131 ispartof: location:Netherlands status: published

Published
2014

14. Fatty acid composition of brain capillary endothelial cells: effect of the coculture with astrocytes

Author

Michel Lagarde, M P Dehouck, R Cecchelli, C Bénistant, J.-C. Fruchart, Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
Endothelium, Linoleic acid, QD415-436, Biology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Phosphatidylcholine, Free fatty acid receptor 1, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, n-6 fatty acids, Phospholipids, 030304 developmental biology, Blood-brain barrier, chemistry.chemical_classification, 0303 health sciences, Fatty acid, Cell Biology, n-3 fatty acids, Endothelial stem cell, medicine.anatomical_structure, chemistry, Docosahexaenoic acid, Arachidonic acid, 030217 neurology & neurosurgery
Abstract

International audience; We have investigated the fatty acid composition of brain capillary endothelial cells cultured alone or in coculture with astrocytes, using an in vitro model in which endothelial cells and astrocytes were grown from one part of a filter to another. We found that the fatty acid composition of the cocultured cerebral endothelial cells was markedly different from that of non-cocultivated endothelial cells. The most striking difference was the increase of arachidonic acid (20:4n-6) at the expense of its precursor, linoleic acid (18:2n-6). Similar modifications were found for the n-3 family of fatty acids with an increase of docosahexaenoic acid (22:6n-3) at the expense of its precursors, but the differences were less than within the n-6 fatty acids. These changes induced by the coculture were observed only in endothelial cell phospholipids, especially the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine classes, but were not detected in phosphatidylinositols and in other lipid classes. Only the composition of the n-3 series fatty acids was altered in another capillary endothelial cell type (from adrenal cortex) cocultured with astrocytes under the same conditions. The fatty acid changes observed might be biologically relevant as they tended to make the fatty acid composition of the brain capillary endothelial cells more closely resemble that of brain microvessels.

Published
1995

15. Study of intracellular anabolism of 5-fluorouracil and incorporation in nucleic acids based on an LC-HRMS method

Author

Anne Vincent, Laetitia Guyot, Maxime Garcia, Béatrice Roy, Jérôme Guitton, Jean-Jacques Diaz, Frédéric Catez, Christelle Machon, Floriane Vanhalle, Nicole Dalla Venezia, Dalla Venezia, Nicole, Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), 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), and Centre National de la Recherche Scientifique (CNRS)

Subjects
Anabolism, Incorporation rate, Metabolite, [SDV]Life Sciences [q-bio], 5-Fluorouracil, Pharmaceutical Science, 02 engineering and technology, Pharmacy, 01 natural sciences, Analytical Chemistry, chemistry.chemical_compound, Drug Discovery, Electrochemistry, Nucleotide, Spectroscopy, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Chemistry, 010401 analytical chemistry, lcsh:RM1-950, RNA, DNA, 021001 nanoscience & nanotechnology, 0104 chemical sciences, 3. Good health, LC-MS-HRMS, Enzyme, lcsh:Therapeutics. Pharmacology, Biochemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Nucleic acid, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Original Article, 0210 nano-technology, Nucleoside
Abstract

5-Fluorouracil (5-FU) is an anticancer drug extensively used for different cancers. Intracellular metabolic activation leads to several nucleoside and nucleotide metabolites essential to exert its cytotoxic activity on multiple cellular targets such as enzymes, DNA and RNA. In this paper, we describe the development of a method based on liquid chromatography coupled with high resolution mass spectrometry suitable for the simultaneous determination of the ten anabolic metabolites (nucleoside, nucleotide and sugar nucleotide) of 5-FU. The chromatographic separation was optimized on a porous graphitic carbon column allowing the analysis of the metabolites of 5-FU as well as endogenous nucleotides. The detection was performed on an Orbitrap® tandem mass spectrometer. Linearity of the method was verified in intracellular content and in RNA extracts. The limit of detection was equal to 12 pg injected on column for nucleoside metabolites of 5-FU and 150 pg injected on column for mono- and tri-phosphate nucleotide metabolites. Matrix effect was evaluated in cellular contents, DNA and RNA extracts for nucleoside and nucleotides metabolites. The method was successfully applied to i) measure the proportion of each anabolic metabolite of 5-FU in cellular contents, ii) follow the consequence of inhibition of enzymes on the endogenous nucleotide pools, iii) study the incorporation of metabolites of 5-FU into RNA and DNA, and iv) to determine the incorporation rate of 5-FUrd into 18 S and 28 S sub-units of rRNA., Graphical abstract Image 1, Highlights • The LC-MS-HRMS method allows the analysis of the ten anabolic metabolites of 5-FU. • The present method is useful to study the incorporation of 5-FU into RNA and DNA. • Method to determine the incorporation rate of 5-FU into subunit of rRNA is innovative.

Published
2021

16. Skull vault hemangioma mimicking neoplastic lesion on [68Ga]Ga-PSMA-11 PET/CT in a patient with glioblastoma: A case report

Author

Alice Bonneville-Levard, Alexandre Basle, Edouard Marie, David Kryza, A. Moreau, Centre Léon Bérard [Lyon], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon

Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, MRI, Magnetic resonance imaging, [SDV]Life Sciences [q-bio], lcsh:R895-920, Calvaria, Case Report, 030218 nuclear medicine & medical imaging, Lesion, Hemangioma, 03 medical and health sciences, SVH, Skull Vault Hemangioma, 0302 clinical medicine, Calvarial hemangioma, [68Ga]Ga-PSMA-11 PET/CT, Cranial vault, medicine, Radiology, Nuclear Medicine and imaging, MIP, Maximum Intensity Projection, SUVmax, maximum standard uptake value, [18F]-F-DOPA PET/CT, 68Ga, PET-CT, business.industry, Neoplastic lesion, [18F]F-DOPA, [18F]F-dihydroxyphenylalanine, medicine.disease, Skull, medicine.anatomical_structure, Radiology, sense organs, medicine.symptom, PET/CT, positron emission tomography/computed tomography, business, Glioblastoma, 030217 neurology & neurosurgery
Abstract

We present the case of a 47-year-old woman treated by radiochimotherapy for a glioblastoma which underwent a [68Ga]Ga-PSMA-11-PET/CT to distinguish postradiation changes from an evolutionary process. This demonstrated a weak homogeneous uptake surrounding the lesion. There was a focal and moderate uptake of a pseudo lytic skull diploe lesion near to the glioblastoma, finally attributed to a calvaria hemangioma. Calvaria hemangiomas are less frequent than vertebral hemangiomas and may demonstrate a modest PSMA uptake that one should keep in mind so as not to misinterpret the examination in patients followed for glioblastomas.

Published
2020

17. Pseudaneurysm of the superolateral genicular artery following an anterior cruciate ligament reconstruction

Author

L. Glanz, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon

Subjects
medicine.medical_specialty, Genicular artery, Complications, Anterior cruciate ligament reconstruction, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pulsatile mass, Vascular injury, Article, Painless Mass, 03 medical and health sciences, Pseudoaneurysm, 0302 clinical medicine, False aneurysm, medicine, Embolization, cardiovascular diseases, business.industry, Meniscal suture, Lateral side, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, cardiovascular system, 030211 gastroenterology & hepatology, Presentation (obstetrics), business, Anterior cruciate ligament
Abstract

Highlights • Pseudoaneurysm of the superolateral genicular artery is a risk in arthroscopic knee procedure. • Pseudoaneurysms risk increase due to minimal invasive procedure. • Ultrasound-guided percutaneous thrombin injection for iatrogenic pseudoaneurysms is a valuable option., Introduction Arthroscopic procedures are a safe way nowadays to do anterior cruciate ligament reconstruction. Rare complications involve injuries to popliteal vessels or one of its branches. Presentation of case We present a case of a young patient who undergone an anterior cruciate ligament reconstruction. This procedure was associated with a meniscal suture. The follow-up was marked by pseudoaneurysm of the supero-lateral genicular artery. Discussion This is the first time a pseudoaneurysm of this branch is described in the literature as we discovered it. The treatment by an ultrasonography-guided embolization with thrombin was proceeded and suceeded. Conclusion We stress the fact with new arthroscopic procedures and techniques, new complications can occur, and we should be attentive to them and new symptoms consequently, as a painless mass on the lateral side of the knee, to ensure a fast and optimal treatment.

Published
2020

18. PRAISE: providing a roadmap for automated infection surveillance in Europe

Author

van Mourik, Maaike S M, van Rooden, Stephanie M, Abbas, Mohamed, Aspevall, Olov, Astagneau, Pascal, Bonten, Marc J M, Carrara, Elena, Gomila-Grange, Aina, de Greeff, Sabine C, Gubbels, Sophie, Harrison, Wendy, Humphreys, Hilary, Johansson, Anders, Koek, Mayke B G, Kristensen, Brian, Lepape, Alain, Lucet, Jean-Christophe, Mookerjee, Siddharth, Naucler, Pontus, Palacios-Baena, Zaira R, Presterl, Elisabeth, Pujol, Miquel, Reilly, Jacqui, Roberts, Christopher, Tacconelli, Evelina, Teixeira, Daniel, Tängdén, Thomas, Valik, John Karlsson, Behnke, Michael, Gastmeier, Petra, PRAISE network, ZonMw, Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, VINNOVA (Sweden), Pfizer, Astellas Pharma, University Medical Center [Utrecht], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Geneva University Hospital (HUG), Public Health Agency of Sweden, Centre d'appui pour la prévention des infections associées aux soins [Île-de-France] (Cpias Île-de-France), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), University of Verona (UNIVR), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Statens Serum Institut [Copenhagen], Public Health Wales, Royal College of Surgeons in Ireland (RCSI), Umeå University, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hammersmith Hospital NHS Imperial College Healthcare, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Biomedicine Institute of Sevilla [Seville, Spain], Medizinische Universität Wien = Medical University of Vienna, Glasgow Caledonian University (GCU), German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Uppsala Universitet [Uppsala], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Freie Universität Berlin, and Humboldt-Universität zu Berlin

Subjects
Infektionsmedicin, Medical care, MESH: Infection Control, Automation, 0302 clinical medicine, MESH: Automation, Bloodstream infection, Infection control, 030212 general & internal medicine, Praise, media_common, 0303 health sciences, Cross Infection, Data, Surveillance, virus diseases, General Medicine, Quality, Infeccions, 3. Good health, Europe, Infectious Diseases, Vigilància electrònica, Epidemiological Monitoring, Electronic surveillance, Medical emergency, Surgical site infection, Microbiology (medical), Healthcare associated infections, Automated, Infectious Medicine, animal structures, media_common.quotation_subject, Electronic health record, Infections, 03 medical and health sciences, medicine, Humans, Healthcare-associated infection, Infection surveillance, Infection Control, MESH: Humans, 030306 microbiology, business.industry, MESH: Cross Infection, medicine.disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Epidemiological Monitoring, MESH: Europe, business
Abstract

[Introduction] Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance – manual chart review – is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care., [Methods] The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts., [Results] This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS., [Conclusions] Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists., This network has been supported under the 7th transnational call within the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Network Call on Surveillance (2018) and was thereby funded by ZonMw (grant 549007001). This project also received support from the COMBACTE MAGNET EPI-Net project funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement 115523 | 115620 | 115737 | 777362, resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. J.K.V. was supported by grants from Region Stockholm and Vinnova. H.H. reports grants from Pfizer and Astellas as well as personal fees from Pfizer outside the submitted work.

Published
2021

19. Investigating the efficacy and safety of metronidazole during pregnancy; A systematic review and meta-analysis

Author

Anil Uzunali, Emmanuelle Ripoche, Emilie Vittaz, Patrick Maison, Thierry Vial, Priscilla Ajiji, Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and VO, alexandra

Subjects
medicine.medical_specialty, Subgroup analysis, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Congenital abnormalities, Pregnancy, Medicine, Premature birth, Obstetrics and Maternal Fetal Medicine, business.industry, Obstetrics, Obstetrics and Gynecology, Odds ratio, Metronidazole/adverse effects, Gynecology and obstetrics, medicine.disease, Low birth weight, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Medicine, Relative risk, Meta-analysis, RG1-991, Gestation, medicine.symptom, business
Abstract

International audience; Objective: We aimed to review and analyze studies focusing on the efficacy of metronidazole in reducing the risk of preterm birth and the safety of metronidazole taking into account the different doses, duration of treatment and routes of administration.Study designs: Embase, Cochrane Library and PubMed were searched up to 29 July 2019 to identify studies assessing metronidazole exposure during pregnancy. Additional studies were identified from reference lists of retrieved papers. Measured outcomes were preterm births (

Published
2021

20. Serum total periostin is an independent marker of overall survival in bone metastases of lung adenocarcinoma

Author

Jean-Baptiste Pialat, Lamia Bouazza, Marie Brevet, Michaël Duruisseaux, O Borel, Jean-Michel Maury, R Guelminger, M. Millet, Philippe Clézardin, Jean-Charles Rousseau, Lauriane Chambard, C Roger, Cyrille B. Confavreux, E Massy, Edith Bonnelye, Evelyne Gineyts, M. Gueye, Nicolas Girard, BONNELYE, Edith, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Claude Bernard Lyon 1 - Faculté des sciences et technologies (UCBL FST), Université de Lyon-Université de Lyon, Hôpital Louis Pradel [CHU - HCL], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers [CRCINA], and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Survival, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diseases of the musculoskeletal system, Periostin, Serum biomarker, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Lung cancer, education, Prospective cohort study, RC254-282, Survival analysis, education.field_of_study, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, bone metastasis, periostin, lung cancer, serum biomarker, survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Bone metastasis, medicine.disease, 3. Good health, 030104 developmental biology, RC925-935, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Adenocarcinoma, Biomarker (medicine), [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, Research Paper
Abstract

International audience; More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients.Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group.The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p

Published
2021

21. Thiamine Deficiency as a Cause for Acute Circulatory Failure: An Overlooked Association in Western Countries

Author

Thomas Bochaton, Nathan Mewton, Mourad Djabou, Ahmad Hayek, Eric Bonnefoy-Cudraz, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, and CarMeN, laboratoire

Subjects
High cardiac output, medicine.medical_specialty, [SDV]Life Sciences [q-bio], CIRCULATORY FAILURE, Case Report, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Acute circulatory failure, Thiamine deficiency, business.industry, food and beverages, Scurvy, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, chemistry, Lactic acidosis, Cardiology, Vascular resistance, Thiamine, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; A 42 year-old patient presented with circulatory failure and lactic acidosis. Clinical features, later coupled with biological tests, led to the diagnosis of wet beriberi syndrome and scurvy. Echocardiography showed a pattern of thiamine deficiency with high cardiac output and low vascular resistance. The patient's condition and biological parameters immediately improved after treatment injections of thiamine. Wet BeriBeri is often overlooked in western countries and is a diagnosis that must be considered based on history, and clinical and echocardiographical findings.

Published
2020

22. Hypertensive choroidopathy: Multimodal imaging and the contribution of wide-field swept-source oct-angiography

Author

Philippe Denis, Amina Rezkallah, Laurent Kodjikian, Amro Abukhashabah, Thibaud Mathis, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], and Hospices Civils de Lyon (HCL)

Subjects
choroidal thickness, visual acuity, Posterior pole, visual impairment, optical coherence tomography angiography, [SPI.MAT]Engineering Sciences [physics]/Materials, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Ophthalmology, Swept-source optical coherence tomography angiography, clinical article, adult, blood pressure, Exudative retinal detachment, Hypertensive choroidopathy, female, retina hemorrhage, spectral domain optical coherence tomography, cerebrospinal fluid pressure, intracranial hypertension, Perfusion, medicine.medical_specialty, B scan, Article, 03 medical and health sciences, slit lamp microscopy, Hypertensive retinopathy, Ophthalmology, Multimodal imaging, Case report, medicine, follow up, human, wide field swept source optical coherence tomography angiography, anterior eye chamber, business.industry, retina detachment, hypertension retinopathy, Retinal, choroid disease, medicine.disease, kidney failure, Blood pressure, chemistry, lcsh:RE1-994, 030221 ophthalmology & optometry, choroid capillary layer, Cerebrospinal fluid pressure, business, 030217 neurology & neurosurgery, intraocular pressure, Myopericarditis
Abstract

Purpose: To present the case of a patient with a hypertensive choroidopathy and her follow-up using multimodal imaging; and to assess how wide-field swept-source (SS) Optical Coherence Tomography Angiography (OCTA) contributes to detecting the areas of hypoperfusion. Observations: A 25-year-old white woman with terminal renal insufficiency, myopericarditis, and cerebrospinal fluid pressure of 37 mmHg indicating intracranial hypertension, presented with a painless loss of vision in both eyes. Her blood pressure was 190/135 mmHg. A thorough diagnosis work-up failed to reveal the etiology. The fundus examination showed arterial narrowing and moderate venous dilation in both eyes. Deep yellow spots were found bilaterally, associated with slight pigment epithelium detachments and exudative retinal detachments. Multimodal imaging showed characteristic features of choroidal involvement in hypertension. Wide-field 12 × 12 mm PlexElite map montage at the choriocapillaris slab identified areas of non-perfusion of the choriocapillaris. These areas mostly correlate with late indocyanine green angiography (ICGA)-presumed choroidal ischemia. During the follow-up, the patient's blood pressure normalized and the choriocapillaris flow improved. Conclusions and importance: In this case of malignant hypertensive retinopathy with exudative retinal detachment of the posterior pole, SS-OCTA showed multiple and widespread flow voids on the choriocapillaris slabs, corresponding to the areas of hypofluorecence on ICGA, demonstrating an associated hypertensive choroidopathy. It would appear that SS-OCTA used alone is capable to show choroidal vascularization impairment in cases of hypertensive retinopathy. Keywords: Hypertensive choroidopathy, Multimodal imaging, Swept-source optical coherence tomography angiography

Published
2019

23. Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?

Author

Brigitte Le Magueresse-Battistoni, Team1 Carmen, Carmen Lab, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-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 Le Magueresse-Battistoni, Brigitte

Subjects
Male, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 0208 environmental biotechnology, Physiology, MESH: Metabolic Diseases, 02 engineering and technology, Endocrine Disruptors, 010501 environmental sciences, Gut flora, 01 natural sciences, Energy homeostasis, Endocrine disrupting chemicals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology, Organic chemicals, Fatty liver, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Pollution, 3. Good health, MESH: Endocrine Disruptors, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, Adult, Environmental Engineering, medicine.drug_class, Endocrine System, Gut microbiota, Sex-dimorphism, Metabolic Diseases, medicine, Humans, Environmental Chemistry, Endocrine system, MESH: Endocrine System, Growth hormone, 0105 earth and related environmental sciences, MESH: Humans, Public Health, Environmental and Occupational Health, MESH: Quality of Life, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipid metabolism, MESH: Adult, General Chemistry, medicine.disease, biology.organism_classification, Estrogen, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, 020801 environmental engineering, Sexual dimorphism, Quality of Life, MESH: Female, MESH: Liver
Abstract

International audience; Endocrine disrupting chemicals (EDCs) are linked to the worldwide epidemic incidence of metabolic disorders and fatty liver diseases, which affects quality of life and represents a high economic cost to society. Energy homeostasis exhibits strong sexual dimorphic traits, and metabolic organs respond to EDCs depending on sex, such as the liver, which orchestrates both drug elimination and glucose and lipid metabolism. In addition, fatty liver diseases show a strong sexual bias, which in part could also originate from sex differences observed in gut microbiota. The aim of this review is to highlight significant differences in endocrine and metabolic aspects of the liver, between males and females throughout development and into adulthood. It is also to illustrate how the male and female liver differently cope with exposure to various EDCs such as bisphenols, phthalates and persistent organic chemicals in order to draw attention to the need to include both sexes in experimental studies. Interesting data come from analyses of the composition and diversity of the gut microbiota in males exposed to the mentioned EDCs showing significant correlations with hepatic lipid accumulation and metabolic disorders but information on females is lacking or incomplete. As industrialization increases, the list of anthropogenic chemicals to which humans will be exposed will also likely increase. In addition to strengthening existing regulations, encouraging populations to protect themselves and promoting the substitution of harmful chemicals with safe products, innovative strategies based on sex differences in the gut microbiota and in the gut-liver axis could be optimistic outlook.

Published
2021

24. INFOGEST inter-laboratory recommendations for assaying gastric and pancreatic lipases activities prior to in vitro digestion studies

Author

Grundy, Myriam M.L., Abrahamse, Evan, Almgren, Annette, Alminger, Marie, Andrés Grau, Ana María, Ariëns, Renata M.C., Bastiaan-Net, Shanna, Bourlieu-Lacanal, Claire, Brodkorb, André, Bronze, Maria R., Comi, Irene, Couëdelo, Leslie, Dupont, Didier, Durand, Annie, El, Sedef N., Grauwet, Tara, Heerup, Christine, Heredia Gutiérrez, Ana Belén, Infantes Garcia, Marcos R., Jungnickel, Christian, Klosowska-Chomiczewska, Ilona E., Letisse, Marion, Macierzanka, Adam, Mackie, Alan R., McClements, David J., Menard, Olivia, Meynier, Anne, Michalski, Marie-Caroline, Mulet-Cabero, Ana-Isabel, Mullertz, Anette, Perello, Francina M. Payeras, Peinado, Irene, Robert, Melina, Secouard, Sebastien, Serra, Ana T., Silva, Sandra D., Thomassen, Gabriel, Tullberg, Cecilia, Undeland, Ingrid, Vaysse, Carole, Vegarud, Gerd E., Verkempinck, Sarah H. E., Viau, Michelle, Zahir, Mostafa, Zhang, Ruojie, Carriere, Frederic, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Danone Nutricia Research [Utrecht], Wageningen University and Research [Wageningen] (WUR), Chalmers University of Technology [Göteborg], Universitat Politècnica de València (UPV), Science et Technologie du Lait et de l'Oeuf (STLO), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Teagasc - The Agriculture and Food Development Authority (Teagasc), Instituto de Biologia Experimental e Tecnológica (IBET), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Faculdade de Farmácia da Universidade de Lisboa, Universidade de Lisboa = University of Lisbon (ULISBOA), Norwegian University of Life Sciences (NMBU), Université de Bordeaux (UB), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ege University - EGE (Izmir, Turkey), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Copenhagen = Københavns Universitet (UCPH), University of Gdańsk (UG), University of Leeds, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Quadram Institute, Biotechnology and Biological Sciences Research Council (BBSRC), Fresenius, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), European Commission COST Action : FA1005 INFOGEST, INRAE, 'Healthy and Safe Food System (KB37) ' knowledge base program of the Dutch Ministry of Agriculture, Nature and Food Quality (LNV) : KB-37-001-007., AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), University of Copenhagen = Københavns Universitet (KU), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Carrière, Frédéric

Subjects
Inhibitor, TECNOLOGIA DE ALIMENTOS, Nutrition. Foods and food supply, [SDV]Life Sciences [q-bio], Lipolysis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, INFOGEST, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV] Life Sciences [q-bio], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Food Quality and Design, TX341-641, Lipases, Enzyme activity, Titration method, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, VLAG, Food, Health & Consumer Research
Abstract

[EN] In vitro digestion studies often use animal digestive enzyme extracts as substitutes of human gastric and pancreatic secretions. Pancreatin from porcine origin is thus commonly used to provide relevant pancreatic enzymes such as proteases, amylase and lipase. Rabbit gastric extracts (RGE) have been recently introduced to provide gastric lipase in addition to pepsin. Before preparing simulated gastric and pancreatic extracts with targeted enzyme activities as described in in vitro digestion protocols, it is important to determine the activities of enzyme preparations using validated methods. The purpose of this inter-laboratory study within the INFOGEST network was to test the repeatability and reproducibility of lipase assays using the pH-stat technique for measuring the activities of gastric and pancreatic lipases from various sources. Twenty-one laboratories having different pH-stat devices received the same protocol with identical batches of RGE and two pancreatin sources. Lipase assays were performed using tributyrin as a substrate and three different amounts (50, 100 and 200 mu g) of each enzyme preparation. The repeatability results within individual laboratories were satisfactory with coefficients of variation (CVs) ranging from 4 to 8% regardless of the enzyme amount tested. However, the inter laboratory variability was high (CV > 15%) compared to existing standards for bioanalytical assays. We identified and weighted the contributions to inter-laboratory variability of several parameters associated with the various pH-stat equipment used in this study (e.g. reaction vessel volume and shape, stirring mode and rate, burette volume for the automated delivery of sodium hydroxide). Based on this, we established recommendations for improving the reproducibility of lipase assays using the pH-stat technique. Defining accurate and complete recommendations on how to correctly quantify activity levels of enzyme preparations is a gateway to promising comparison of in vitro data obtained from different laboratories following the same in vitro digestion protocol., The authors thank the European Commission COST Action FA1005 INFOGEST and INRAE for financing the meetings and conferences that enable the 21 laboratories to network and organise the work presented in this article. We also acknowledge the 'Healthy and Safe Food System (KB37) ' knowledge base program of the Dutch Ministry of Agriculture, Nature and Food Quality (LNV) , with grant number KB-37-001-007 for funding of this work performed at Wageningen Food & Biobased Research. We are grateful to Dr Sawsan Amara (CEO of Lipolytech SA., Marseille, France) for her generous gift of RGE and to Drs Jan Ludemann, Anja Jensen, Olaf Friedrich and Claus Middelberg from Nordmark Arzneimittel GmbH & Co. KG (Uetersen, Germany) for their generous gift of Nordmark pancreatin. Finally, we thank Drs Maria Fatima Cabral and Judite Costa from iBET for their technical support and discussion.

Published
2021

25. Role of mitochondria-associated endoplasmic reticulum membrane (MAMs) interactions and calcium exchange in the development of type 2 diabetes

Author

Florian Dingreville, Johan Perrier, Baptiste Panthu, Anne-Marie Madec, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-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 CarMeN, laboratoire

Subjects
Calcium, [SDV]Life Sciences [q-bio], Cell, er, Mitochondrion, Biology, Endoplasmic Reticulum, Mitochondria, Insulin-Secreting Cells, Organelle, medicine, Animals, Humans, Glucose homeostasis, Secretion, Glucotoxicity, of interest, Type 2 Diabetes, Endoplasmic reticulum membrane, β cells, Endoplasmic reticulum, Intracellular Membranes, Cell biology, [SDV] Life Sciences [q-bio], Crosstalk (biology), Glucose, medicine.anatomical_structure, Diabetes Mellitus, Type 2, MAMs
Abstract

International audience; Glucotoxicity-induced β-cell dysfunction in type 2 diabetes is associated with alterations of mitochondria and the endoplasmic reticulum (ER). Mitochondria and ER form a network in cells that controls cell function and fate. Mitochondria of the pancreatic β cell play a central role in the secretion of insulin in response to glucose through their ability to produce ATP. Both organelles interact at contact sites, defined as mitochondria-associated membranes (MAMs), which were recently implicated in the regulation of glucose homeostasis. Here, we review MAM functions in the cell and we focus on the crosstalk between the ER and Mitochondria in the context of T2D, highlighting the pivotal role played by MAMs especially in β cells through inter-organelle calcium exchange and glucotoxicity-associated β cell dysfunction.

Published
2021

26. Calcium Repletion and Regional Citrate Anticoagulation in Hemodialysis and Hemodiafiltration: Using Dialysate Calcium to Modify Hypocalcemia

Author

Justin R. Dorie, Christopher W. McIntyre, Sandrine Lemoine, University of Western Ontario (UWO), Lawson Health Research Institute, London Health Sciences Center (LHSC), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-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 CarMeN, laboratoire

Subjects
medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Urology, chemistry.chemical_element, Calcium, Dialysate calcium, Diseases of the genitourinary system. Urology, [SDV] Life Sciences [q-bio], chemistry, Nephrology, Correspondence, Internal Medicine, Research Letter, Medicine, Citrate anticoagulation, Hemodialysis, RC870-923, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; No abstract available

Published
2021

27. The impact of a visual spatial frame on real sound-source localization in virtual reality

Author

Michela Todeschini, Alessandro Farnè, Mariam Alzhaler, Francesco Pavani, Valérie Gaveau, Romeo Salemme, Mathieu Marx, Gregoire Verdelet, Chiara Valzolgher, Elena Gessa, Eric Truy, Pascal Barone, Pauline Nieto, Integrative, Multisensory, Perception, Action and Cognition Team [Bron] (IMPACT), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Trento [Trento], and Hospices Civils de Lyon (HCL)

Subjects
Sound localization, Computer science, lcsh:BF1-990, Kinematics, Gaze tracking, Virtual reality, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Active listening, 0501 psychology and cognitive sciences, Computer vision, Spatial hearing, Sensory cue, business.industry, 05 social sciences, Visual information, Head movements tracking, General Medicine, Acoustic source localization, Grid, lcsh:Psychology, [SCCO.PSYC]Cognitive science/Psychology, Sound emission, Sound sources, Artificial intelligence, business, 030217 neurology & neurosurgery
Abstract

International audience; Studies on audiovisual interactions in sound localization have primarily focused on the relations between the spatial position of sounds and their perceived visual source, as in the famous ventriloquist effect. Much less work has examined the effects on sound localization of seeing aspects of the visual environment. In this study, we took advantage of an innovative method for the study of spatial hearing-based on real sounds, virtual reality and real-time kinematic tracking-to examine the impact of a minimal visual spatial frame on sound localization. We tested sound localization in normal hearing participants (N = 36) in two visual conditions: a uniform gray scene and a simple visual environment comprising only a grid. In both cases, no visual cues about the sound sources were provided. During and after sound emission, participants were free to move their head and eyes without restriction. We found that the presence of a visual spatial frame improved hand-pointing in elevation. In addition, it determined faster first-gaze movements to sounds. Our findings show that sound localization benefits from the presence of a minimal visual spatial frame and confirm the importance of combining kinematic tracking and virtual reality when aiming to reveal the multisensory and motor contributions to spatial-hearing abilities.

Published
2020

28. Reverse phenotyping in patients with skin capillary malformations and mosaic GNAQ or GNA11 mutations defines a clinical spectrum with genotype-phenotype correlation

Author

Christophe Philippe, Florence Petit, Justine Pasteur, Sandra Whalen, J. Mazereeuw, Nenad Bukvic, Annabel Maruani, Arthur Sorlin, Marjolaine Willems, V. Carmignac, Emmanuelle Bourrat, Alice Goldenberg, Maud Jordan, Pierre Vabres, Smail Hadj-Rabia, Marine Fournet, Bruno Delobel, Jehanne Martel, Anne-Claire Bursztejn, Alice Phan, Fanny Morice-Picard, Cyril Mignot, Luca Borradori, Odile Boute, Paul Kuentz, Antoine Mahé, Marie-Laure Moutard, Juliette Albuisson, Christine Chiaverini, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nice (CHU Nice), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), CHU Bordeaux [Bordeaux], CHU Dijon, Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Bern University Hospital [Berne] (Inselspital), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Université catholique de Lille (UCL), Université de Bourgogne (UB), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), CH Colmar, CHU Toulouse [Toulouse], CHU Trousseau [APHP], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Capillary malformation, Adolescent, Vascular Malformations, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, 610 Medicine & health, Dermatology, Biochemistry, Correlation, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, In patient, Child, Molecular Biology, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, Skin, 0303 health sciences, GNA11, business.industry, Mosaicism, Infant, Cell Biology, Skin capillary, Middle Aged, medicine.disease, Phenotype, GTP-Binding Protein alpha Subunits, Vascular Neoplasms, Phakomatosis pigmentovascularis, Child, Preschool, Genotype-Phenotype Correlation, GTP-Binding Protein alpha Subunits, Gq-G11, Female, business, GNAQ
Abstract

International audience; No abstract available

Published
2020

29. Combined Liver-Kidney Transplantation With Preformed Anti-human Leukocyte Antigen Donor-Specific Antibodies

Author

Nassim Kamar, Camille Besch, Olivier Thaunat, Jérôme Dumortier, Philippe Gatault, Moglie Le Quintrec, Louise Barbier, Antoine Durrbach, Laura Lladó, Frédéric Jambon, Georges-Philippe Pageaux, Martine Neau-Cransac, Arnaud Del Bello, Oriol Bestard, Peggy Perrin, Cognata, Bérangère, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Strasbourg, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation (FHU SUPORT), 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)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT)-Université de Tours (UT)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Edouard Herriot [CHU - HCL], CHU Toulouse [Toulouse], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM)- 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)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT)-Université de Tours (UT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), and Université de Tours-Université de Tours

Subjects
medicine.medical_specialty, 030232 urology & nephrology, graft survival, Ronyó, Renal function, Human leukocyte antigen, 030204 cardiovascular system & hematology, Kidney, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, combined liver-kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Fetge, Clinical Research, Internal medicine, medicine, Transplantation of organs, biology, business.industry, Hazard ratio, Retrospective cohort study, donor-specific antibody, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Confidence interval, 3. Good health, Transplantation, Trasplantament d'òrgans, medicine.anatomical_structure, Rebuig (Biologia), Liver, Nephrology, Graft rejection, biology.protein, Antibody, rejection, business
Abstract

Introduction The impact of preformed donor-specific anti–human leukocyte antigen (HLA) antibodies (pDSAs) after combined liver-kidney transplantation (CLKT) is still uncertain. Methods We conducted a retrospective study in 8 European high-volume transplant centers and investigated the outcome of 166 consecutive CLKTs, including 46 patients with pDSAs. Results Patient survival was lower in those with pDSAs (5-year patient survival rate of 63% and 78% with or without pDSA, respectively; P = 0.04). The presence of pDSAs with a mean fluorescence intensity (MFI) ≥ 5000 (hazard ratio 4.96; 95% confidence interval: 2.3–10.9; P < 0.001) and the presence of 3 or more pDSAs (hazard ratio 6.5; 95% confidence interval: 2.5–18.8; P = 0.05) were independently associated with death. The death-censored liver graft survival was similar in patients with or without pDSAs. Kidney graft survival was comparable in both groups. (The 1- and 5-year death-censored graft survival rates were 91.6% and 79.5%, respectively, in patients with pDSAs and 93% and 88%, respectively, in the donor-specific antibody [DSA]-negative group, P = not significant). Despite a higher rate of kidney graft rejection in patients with pDSAs (5-year kidney graft survival rate without rejection of 87% and 97% with or without pDSAs, respectively; P = 0.04), kidney function did not statistically differ between both groups at 5 years post-transplantation (estimated glomerular filtration rate 45 ± 17 vs. 57 ± 29 ml/min per 1.73 m2, respectively, in patients with and without pDSAs). Five recipients with pDSAs (11.0%) experienced an antibody-mediated kidney rejection that led to graft loss in 1 patient. Conclusion Our results suggest that CLKT with pDSAs is associated with a lower patients’ survival despite good recipients’, liver and kidney grafts’ outcome., Graphical abstract

Published
2020

30. Population and evolutionary genetics of the PAH locus to uncover overdominance and adaptive mechanisms in phenylketonuria: Results from a multiethnic study

Author

Oussalah, Abderrahim, Jeannesson-Thivisol, Elise, Chery, Céline, Perrin, Pascal, Rouyer, Pierre, Josse, Thomas, Cano, Aline, Barth, Magalie, Fouilhoux, Alain, Mention, Karine, Labarthe, François, Arnoux, Jean-Baptiste, Maillot, François, Lenaerts, Catherine, Dumesnil, Cécile, Wagner, Kathy, Terral, Daniel, Broue, Pierre, de Parscau, Loïc, Gay, Claire, Kuster, Alice, Bedu, Antoine, Besson, Gérard, Lamireau, Delphine, Odent, Sylvie, Masurel, Alice, Rodriguez-Guéant, Rosa-Maria, Feillet, François, Guéant, Jean-Louis, Namour, Fares, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Hôpitaux Pédiatriques de Nice Lenval (CHU-Lenval), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital des Enfants, CHU Toulouse [Toulouse], CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie médicale - réanimation et néonatologie [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Pontchaillou [Rennes], Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), DE CARVALHO, Philippe, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Male, Research paper, [SDV]Life Sciences [q-bio], lcsh:Medicine, Metabolic adaptation, Gene Frequency, Phenylketonurias, Overdominance, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Ethnicity, Humans, Phenylketonuria, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Exome, Genetic Association Studies, Phylogeny, Principal Component Analysis, lcsh:R5-920, Geography, lcsh:R, Phenylalanine Hydroxylase, Biological Evolution, [SDV] Life Sciences [q-bio], Balancing selection, Genetics, Population, Haplotypes, Genetic Loci, Population divergence, Female, France, lcsh:Medicine (General)
Abstract

Background: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism in Europe. The reasons underlying the high prevalence of heterozygous carriers are not clearly understood. We aimed to look for pathogenic PAH variant enrichment according to geographical areas and patients’ ethnicity using a multiethnic nationwide cohort of patients with PKU in France. We subsequently appraised the population differentiation, balancing selection and the molecular evolutionary history of the PAH locus. Methods: The French nationwide PKU study included patients who have been referred at the national level to the University Hospital of Nancy, and for whom a molecular diagnosis of phenylketonuria was made by Sanger sequencing. We performed enrichment analyses by comparing alternative allele frequencies using Fisher's exact test with Bonferroni adjustment. We estimated the amount of genetic differentiation among populations using Wright's fixation index (Fst). To estimate the molecular evolutionary history of the PAH gene, we performed phylogenetic and evolutionary analyses using whole-genome and exome-sequencing data from healthy individuals and non-PKU patients, respectively. Finally, we used exome-wide association study to decipher potential genetic loci associated with population divergence on PAH. Findings: The study included 696 patients and revealed 132 pathogenic PAH variants. Three geographical areas showed significant enrichment for a pathogenic PAH variant: North of France (p.Arg243Leu), North-West of France (p.Leu348Val), and Mediterranean coast (p.Ala403Val). One PAH variant (p.Glu280Gln) was significantly enriched among North-Africans (OR = 23·23; 95% CI: 9·75–55·38). PAH variants exhibiting a strong genetic differentiation were significantly enriched in the ‘Biopterin_H’ domain (OR = 6·45; 95% CI: 1·99–20·84), suggesting a balancing selection pressure on the biopterin function of PAH. Phylogenetic and timetree analyses were consistent with population differentiation events on European-, African-, and Asian-ancestry populations. The five PAH variants most strongly associated with a high selection pressure were phylogenetically close and were located within the biopterin domain coding region of PAH or in its vicinity. Among the non-PAH loci potentially associated with population divergence, two reached exome-wide significance: SSPO (SCO-spondin) and DBH (dopamine beta-hydroxylase), involved in neuroprotection and metabolic adaptation, respectively. Interpretation: Our data provide evidence on the combination of evolutionary and adaptive events in populations with distinct ancestries, which may explain the overdominance of some genetic variants on PAH. Funding: French National Institute of Health and Medical Research (INSERM) UMR_S 1256. Keywords: Phenylketonuria, Balancing selection, Population divergence, Overdominance, Metabolic adaptation

Published
2020

31. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Author

Douglas Cunningham, D. Ward, Mamta K. Jain, Faiza Ajana, Magda Opsomer, Anita Rachlis, Sharon Walmsley, Frank A. Post, Anders Blaxhult, Amanda Clarke, M. J. Galindo, Marcel Stoeckle, P.-M. Girardy, Karam Mounzer, David Shamblaw, U. F. Bredeek, L. Bhatti, J. J. Eron, Andrew Ustianowski, Mar Gutierrez, John Jezorwski, Javier O Morales-Ramirez, Antonio Rivero, M.A. Johnson, Gatell Jm, Erika Van Landuyt, Stéphane De Wit, A. Wilkin, Laurent Cotte, Cheryl McDonald, D. Murphy, Cynthia Brinson, Romana Petrovic, Olayemi Osiyemi, J. de Vente, I. Poizot-Martin, Juan Berenguer, Robin Dretler, J. Bailey, B. Rashbaum, Moti Ramgopal, A. Scribner, Yazdan Yazdanpanah, Eric Florence, A. Piekarska, Brian Gazzard, Chloe Orkin, W. Halota, Gary Richmond, Jacques Reynes, C. Ricart, C. Lucasti, Ignacio Pérez-Valero, Jason Brunetta, S. Shafran, Daniel Podzamczer, Franco Antonio Felizarta, Claudia Martorell, F. Post, Peter Ruane, Edwin DeJesus, J. Portilla Sogorb, C. Orkin, K. Tashima, Federico Pulido, Bernard Vandercam, F. Pulido, José L. Casado, Christine Katlama, Kimberley Brown, J Gasiorowski, A. Witor, Joseph J. Eron, Brian Conway, Andri Rauch, Jose R. Arribas, Michel Moutschen, H. Olivet, A. Scarsella, Leo Flamholc, A. Horban, D. Cunningham, Ronald Nahass, Félix Gutiérrez, G. Huhn, W.K. Henry, A. Thalme, S De Wit, Jan Fehr, Debbie Hagins, José Antonio Iribarren, J.-M. Molina, S. Henn, F Raffi, Juan A. Pineda, Marina B. Klein, Eugenia Negredo, Hernando Knobel, J. Slim, P. Benson, L. Waters, E. Teicher, Linos Vandekerckhove, Craig A. Dietz, Magnus Gisslén, Joel E. Gallant, J. Gathe, P. Shalit, D. Prelutsky, G. Voskuhl, D. Rey, E. Van Wijngaerden, Anthony Mills, Erkki Lathouwers, Carl J. Fichtenbaum, I. Brar, Gordon Crofoot, Veerle Hufkens, I. Santos Gil, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Queen Mary University of London (QMUL), Pueblo Family Physicians, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), King's College Hospital (KCH), Université libre de Bruxelles (ULB), Janssen Pharmaceutica [Beerse], Janssen Research & Development, Institute of Tropical Medicine [Antwerp] (ITM), Department of Infectious and Parasitic Diseases (University Liege), Université de Liège, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Living Hope Foundation, Ghent University Hospital, Cliniques Universitaires Saint-Luc [Bruxelles], Maple Leaf Clinic, Vancouver Infectious Diseases Centre, McGill University = Université McGill [Montréal, Canada], University of Toronto, Sunnybrook Health Sciences Centre, University of Alberta, University Health Network, Services des maladies infectieuses [Tourcoing], Centre Hospitalier de Tourcoing, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Wrocław [Poland] (UWr), Faculty of Medicine [Bydgoszcz, Poland], Nicolaus Copernicus University [Toruń], Medical University of Warsaw - Poland, Medical University of Łódź (MUL), Regional Hospital [Chorzow, Poland], La Paz Hospital, IdiPAZ, Hospital General Universitario 'Gregorio Marañón' [Madrid], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Infectious Diseases Service, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain., Hospital Universitario de Elche, Hospital Universitario de Valencia, Hospital de la Santa Creu i Sant Pau, Donostia Hospital Universitario San Sebastian, IMIM-Hospital del Mar, Generalitat de Catalunya, LLuita contra la Sida Fdn-HIV Unit, Germans Trias i Pujol University Hospital- Universitat Autònoma de Barcelona, Hospital Universitario de Valme, Hospital Universitari de Bellvitge, Universitat de València (UV), Hospital Universitario Reina Sofía, Hospital La Princesa, Madrid, Karolinska Institutet, Södersjukhuset, Skane University Hospital [Malmo], Lund University [Lund], University of Gothenburg (GU), Karolinska University Hospital [Stockholm], University hospital of Zurich [Zurich], Bern University Hospital [Berne] (Inselspital), University Hospital Basel [Basel], Royal Sussex County Hospital, Chelsea and Westminster Hospital, North Manchester General Hospital, University College of London [London] (UCL), Johns Hopkins University School of Medicine [Baltimore], Be Well, AIDS healthcare foundation [California], Henry Ford Hospital, Metropolis Medical, Central Texas Clinical Research, The Crofoot Research Center, Orlando Immunology Center, Kansas City Free Health Clinic, University of Cincinnati (UC), University of Minnesota System, University of Texas Southwestern Medical Center, South Jersey Infectious Disease, Infectious Disease, Tarrant County Infectious Disease Associates, Southern California Men’s Medical Group, Clinical Research Puerto Rico Inc, Philadelphia FIGHT, ID care, Community Research Initiative of New England, Triple O Research Institute PA, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Midway Immunology Center, Capital Medical Associates, Broward General Medical Center, Ruane Clinical Research Group, Pacific Oaks Medical Group, DCOL Center for Clinical Research, Peter Shalit MD and Associates, La Playa Medical Group, Seton Hall University, Warren Alpert Medical School of Brown University, AIDS Arms, Inc, Dupont Circle Physicians Group, Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hospital Universitario Donostia [San Sebastian, Spain] (HUD), Universitat Autònoma de Barcelona (UAB), Hospital Universitario de La Princesa, HAL AMU, Administrateur, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service de médecine interne générale

Subjects
Male, DOLUTEGRAVIR, Sustained Virologic Response, HIV Infections, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Medicine and Health Sciences, Emtricitabine, 030212 general & internal medicine, Pharmacology & Pharmacy, Darunavir, 0303 health sciences, Alanine, Drug Substitution, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Lamivudine, Antiretrovirals, Middle Aged, Viral Load, OPEN-LABEL, 3. Good health, WEIGHT-GAIN, Drug Combinations, Treatment Outcome, Dolutegravir, NON-INFERIORITY, Female, Safety, Viral load, Life Sciences & Biomedicine, medicine.drug, Tablets, Adult, medicine.medical_specialty, Efficacy, Anti-HIV Agents, RITONAVIR, TENOFOVIR ALAFENAMIDE, LAMIVUDINE, Tenofovir alafenamide, Single-tablet regimen, 03 medical and health sciences, Internal medicine, Virology, medicine, VIH (Virus), Humans, Switch study, Protease Inhibitors, Tenofovir, Aged, Pharmacology, Science & Technology, 030306 microbiology, business.industry, HIV (Viruses), Adenine, Darunavir/cobicistat/emtricitabine/TAF, Antiretroviral agents, COBICISTAT, MAINTENANCE, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, Ritonavir, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, RESISTANCE
Abstract

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL

Published
2019

32. Comparison of transcatheter to surgical aortic valve implantation in high risk patients : a nationwide study in France

Author

Jean-François Obadia, Stéphanie Polazzi, Léa Pascal, Antoine Duclos, Xavier Armoiry, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), ONERA - The French Aerospace Lab [Toulouse], ONERA, Département d'information médicale, and Hospices Civils de Lyon (HCL)-Université de Lyon

Subjects
Aortic valve, proportional hazards model, clinical outcome, heart failure, morbidity, high risk patient, 030204 cardiovascular system & hematology, [SPI.MAT]Engineering Sciences [physics]/Materials, cause of death, FIne and Gray competing risk model, hazard ratio, 0302 clinical medicine, Aortic valve replacement, Risk of mortality, Medicine, 030212 general & internal medicine, Cause of death, adult, Hazard ratio, hospitalization cost, longitudinal study, health care cost, risk assessment, cohort analysis, 3. Good health, aged, female, medicine.anatomical_structure, priority journal, Cardiology, France, cerebrovascular accident, Cardiology and Cardiovascular Medicine, Cohort study, Pulmonary and Respiratory Medicine, medicine.medical_specialty, heart infarction, Article, 03 medical and health sciences, male, statistical analysis, Internal medicine, follow up, aortic valve replacement, controlled study, human, intermethod comparison, outcome assessment, propensity score, transcatheter aortic valve implantation, hospital mortality, business.industry, Proportional hazards model, EuroSCORE, aortic valve disease, medicine.disease, major clinical study, multicenter study, confidence interval, pacemaker implantation, Surgery, business, RD, RC
Abstract

cited By 3; International audience; Objective: To compare the clinical outcomes and direct costs at 5 years between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) using real-world evidence. Methods: We performed a nationwide longitudinal study using data from the French Hospital Information System from 2009 to 2015. We matched, inside hospitals, 2 cohorts of adults who underwent TAVI or SAVR during 2010 on propensity score based on patient characteristics. Outcomes analysis included mortality, morbidity, and total costs and with a maximum 60-month follow-up. Clinical outcomes were compared between cohorts using hazard ratios (HRs) estimated from a Cox proportional hazards model for all-cause death, and from Fine and Gray's competing risk model for morbidity. Results: Based on a cohort of 1598 patients (799 in each group) from 27 centers, a higher risk of death was observed after 1 year with TAVI compared with SAVR (16.8% vs 12.8%, respectively; HR, 1.33; 95% confidence interval [CI], 1.02-1.72) and was sustained up to 5 years (52.4% vs 37.2%; HR, 1.56; 95% CI, 1.33-1.84). At 5 years, the risk of stroke was increased (HR, 1.64; 95% CI, 1.07-2.54) as was myocardial infarction (HR, 2.30; 95% CI, 1.12-4.69) and pacemaker implantation (HR, 2.40; 95% CI, 1.81-3.17) after TAVI. The hospitalization costs per patient at 5 years were €69,083 after TAVI and €55,687 after SAVR (P

Published
2018

33. Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population

Author

Ashok Varma, Kathrin Tintelnot, Patricia Escandón, Tomoe Ichikawa, Aristea Velegraki, Volker Rickerts, Alberto Zani, Reiko Ikeda, Ilka McCormick, Anne-Lise Bienvenu, Sevim Akcaglar, Massimo Cogliati, Anna Maria Tortorano, Okan Töre, Marie Desnos-Ollivier, Shawn R. Lockhart, Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı., Töre, Okan, Akçağlar, Sevim, Università degli Studi di Milano = University of Milan (UNIMI), Robert Koch Institute [Berlin] (RKI), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), National and Kapodistrian University of Athens (NKUA), Instituto Nacional de Salud [Bogota], Meiji Pharmaceutical University, Hospices Civils de Lyon (HCL), Université de Lyon, Uludağ Üniversitesi = Uludag University, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, National Institutes of Health [Bethesda] (NIH), We thank Prof. F. Dromer and Prof. J. Kwon-Chung for providing some of the isolates and for her suggestions to improve this study, and Dr. T. Boekhout and Dr. B. Theelen for sequencing support., Università degli Studi di Milano [Milano] (UNIMI), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Serotype, C neoformans var grubii, Serotypes, Denmark, Cryptococcus Gattii, Flucytosine, Cryptococcus Neoformans, Cryptococcus, Molecular typing, Population structure, Turkey (republic), law.invention, MESH: Genotype, Species complex, Belgium, Japan, law, Germany, Genotype, MESH: Genetic Variation, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Phylogeny, Priority journal, education.field_of_study, Phylogenetic tree, biology, Greece, MESH: Asia, Genetics & heredity, C. neoformans var. neoformans, Correlation analysis, MESH: Cryptococcus neoformans, Gene linkage disequilibrium, Cryptococcosis, Thailand, Classification, 3. Good health, Europe, Phylogeography, MESH: Multilocus Sequence Typing, Italy, MESH: Phylogeography, Molecular epidemiology, Recombinant DNA, MESH: Recombination, Genetic, Microbiological examination, France, MLST, Asia, 030106 microbiology, Population, C neoformans var neoformans, Multilocus sequence typing, MESH: Cryptococcosis, Mycology, Recombination, genetic, Colombia, Microbiology, Mating-type, Article, 03 medical and health sciences, C. neoformans var. grubii, C neoformans var. grubii, MESH: Mycological Typing Techniques, Genetics, MESH: Americas, Cutaneous cryptococcosis, Genetic variation, Western hemisphere, education, Cryptococcus neoformans, Genetic recombination, Mycological typing techniques, biology.organism_classification, Nonhuman, Recombination, United States, Gattii, 030104 developmental biology, Isolation and purification, Geographic origin, Fungus isolation, Genetic variability, MESH: Europe, Americas, Varietas
Abstract

Cryptococcus neoformans var. neoformans (serotype D) represents about 30% of the clinical isolates in Europe and is present less frequently in the other continents. It is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. Very little is known about the genotypic diversity of this Cryptococcus subtype. The aim of this study was to investigate the genotypic diversity among a set of clinical and environmental C. neoformans var. neoformans isolates and to evaluate the relationship between genotypes, geographical origin and clinical manifestations. A total of 83 globally collected C neoformans var. neoformans isolates from Italy, Germany, France, Belgium, Denmark, Greece, Turkey, Thailand, Japan, Colombia, and the USA, recovered from different sources (primary and secondary cutaneous cryptococcosis, disseminated cryptococcosis, the environment, and animals), were included in the study. All isolates were confirmed to belong to genotype VNIV by molecular typing and they were further investigated by MLST analysis. Maximum likelihood phylogenetic as well as network analysis strongly suggested the existence of a recombinant rather than a clonal population structure. Geographical origin and source of isolation were not correlated with a specific MLST genotype. The comparison with a set of outgroup C neoformans var. grubii isolates provided clear evidence that the two varieties have different population structures. United States Department of Health & Human Services - Z99 AI999999 - P41 RR001646 National Institutes of Health (NIH) - USA NIH National Center for Research Resources (NCRR)

Published
2016

34. Preclinical investigation of the effect of stress on the binding of [ 18 F]F13640, a 5-HT 1A radiopharmaceutical.

Author

Courault P, Bouvard S, Bouillot C, Zimmer L, and Lancelot S

Abstract

Background: [ 18 F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT 1A receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT 1A receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [ 18 F]FDG and then proceeded to test for effects of this model on the cerebral binding of [ 18 F]F13640, a 5-HT 1A receptors PET radiopharmaceutical., Methods: Four groups of male Sprague-Dawley were used to identify the optimal model: "stressed group" (n = 10), "post-traumatic stress disorder (PTSD) group" (n = 9) and "restraint group" (n = 8), compared with a control group (n = 8). All rats performed neuroimaging [ 18 F]FDG μPET-CT to decipher which model was the most appropriate to test effects of stress on radiotracer binding. Subsequently, a group of rats (n = 10) underwent two PET imaging acquisitions (baseline and PTSD condition) using the PET radiopharmaceutical [ 18 F]F13640 to assess influence of stress on its binding. Voxel-based analysis was performed to assess [ 18 F]FDG or [ 18 F]F13640 changes., Results: In [ 18 F]FDG experiments, the PTSD group showed a pattern of cerebrometabolic activation in various brain regions previously implicated in stress (amygdala, perirhinal cortex, olfactory bulb and caudate). [ 18 F]F13640 PET scans showed increased radiotracer binding in the PTSD condition in caudate nucleus and brainstem., Conclusions: The present study demonstrated stress-induced cerebrometabolic activation or inhibition of various brain regions involved in stress model. Applying this model to our radiotracer, [ 18 F]F13640 showed few influence of stress on its binding. This will enable to rule out any confounding effect of stress during imaging studies., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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35. The experience of diagnosis announcement in rare endocrine diseases: A survey of the French FIRENDO network.

Author

Rahabi H, Givony M, Demaret B, Albarel F, Aubron MR, Bartès B, Bernard L, Abdoul H, Bouazza N, Brun P, Drui D, Dujardin V, Lançon C, Malivoir S, Netchine I, Perrotin B, Picard V, Reynaud R, Ribeiro M, Tardy Guidollet V, Victor A, Bertherat J, Colin C, and Brue T

Subjects
Adult, Child, Humans, Rare Diseases diagnosis, Rare Diseases therapy, Surveys and Questionnaires, Endocrine System Diseases diagnosis, Endocrine System Diseases therapy, Cushing Syndrome, Adrenal Hyperplasia, Congenital
Abstract

Context: Diagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step in the management of severe conditions such as rare endocrine diseases. Little is known of how diagnosis is communicated to patients and families. The FIRENDO network was created by the third French Plan for Rare Diseases, to promote autonomy, care and research on rare endocrine diseases., Objectives: The aim of this study was to characterize, for the first time, the experience and needs of patients and/or their parents around the announcement of diagnosis to ensure optimal quality of care., Methods: A quantitative self-administered survey on diagnosis announcement procedures in rare endocrine diseases was launched in April 2017 by the ad hoc FIRENDO thematic working group in collaboration with its 11 partnering patient associations and support groups. The questionnaire was designed and revised by patient support group representatives, adult and pediatric endocrinologists, psychologists and biologists, all expert in rare endocrine diseases. It was made available on the FIRENDO network website and distributed mainly by email with electronic links on their respective websites to members of all affiliated patient support groups., Results: Questionnaires were filled out by 391 patients and 223 parents (median age of patients: 39 years). The following conditions were associated with at least 30 answers: Addison's disease, classical forms of congenital adrenal hyperplasia (CAH), Russell-Silver syndrome, Cushing's syndrome, acromegaly and craniopharyngioma. Overall, some announcement modalities were judged favorably by patients: physician's empathy, availability and use of clear terms, and presence of family at the time of announcement. However, a lack of psychological care and information documents was reported, as well as some inadequate procedures such as postal mail announcements., Conclusion: This work suggests that better knowledge of the patient's experience is useful for improving the diagnosis announcement of rare endocrine disorders. The main recommendations derived from the survey were the need for several announcement visits, information on patient support groups and reference centers, imperatively avoiding impersonal announcement, and the usefulness of a written accompanying document., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Published
2024
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36. Carotenoids in familial hypobetalipoproteinemia disorders: Malabsorption in Caco2 cell models and severe deficiency in patients.

Author

Bordat C, Cuerq C, Halimi C, Vairo D, Blond E, Restier L, Poinsot P, Duclaux-Loras R, Peretti N, and Reboul E

Subjects
Humans, Caco-2 Cells, Zeaxanthins metabolism, Carotenoids metabolism, Vitamins, Lipids, Hypobetalipoproteinemias genetics, Monomeric GTP-Binding Proteins genetics, Syndactyly
Abstract

Background: Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3), caused by mutations in microsomal triglyceride transfer protein (MTTP) and SAR1B genes, respectively. Treatments include a low-fat diet and high-dose fat-soluble vitamin supplementations. However, patients are not supplemented in carotenoids, a group of lipid-soluble pigments essential for eye health., Objective: Our aim was to evaluate carotenoid absorption and status in the context of hypobetalipoproteinemia., Methods: We first used knock-out Caco-2/TC7 cell models of FHBL-SD1 and FHBL-SD3 to evaluate carotenoid absorption. We then characterized FHBL-SD1 and FHBL-SD3 patient status in the main dietary carotenoids and compared it to that of control subjects., Results: In vitro results showed a significant decrease in basolateral secretion of α- and β-carotene, lutein, and zeaxanthin (-88.8 ± 2.2 % to -95.3 ± 5.8 %, -79.2 ± 4.4 % to -96.1 ± 2.6 %, -91.0 ± 4.5 % to -96.7 ± 0.3 % and -65.4 ± 3.6 % to -96.6 ± 1.9 %, respectively). Carotenoids plasma levels in patients confirmed significant deficiencies, with decreases ranging from -89 % for zeaxanthin to -98 % for α-carotene, compared to control subjects., Conclusion: Given the continuous loss in visual function despite fat-soluble vitamin treatment in some patients, carotenoid supplementation may be of clinical utility. Future studies should assess the correlation between carotenoid status and visual function in aging patients and investigate whether carotenoid supplementation could prevent their visual impairment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Published
2024
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37. Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis.

Author

Rousset-Jablonski C, Mekki Y, Denis A, Reynaud Q, Nove-Josserand R, Durupt S, Touzet S, Perceval M, Ray-Coquard I, Golfier F, and Durieu I

Subjects
Adult, Humans, Female, Adolescent, Young Adult, Middle Aged, Human Papillomavirus Viruses, Prospective Studies, Prevalence, Early Detection of Cancer, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms prevention & control, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Cystic Fibrosis epidemiology, Uterine Cervical Dysplasia diagnosis, Uterine Cervical Dysplasia epidemiology
Abstract

Background: A higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF)., Methods: We conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology., Results: We included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients., Conclusion: Transplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Published
2023
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38. A 3-Year Course Of Bulevirtide Monotherapy May Cure Hdv Infection In Cirrhotics.

Author

Anolli MP, Degasperi E, Allweiss L, Sangiovanni A, Maggioni M, Scholtes C, Oberhardt V, Neumann-Haefelin C, Dandri M, Zoulim F, and Lampertico P

Abstract

Bulevirtide has been recently conditionally approved by the European Medicines Agency for the treatment of Chronic Hepatitis Delta, but the ideal duration of therapy is unknown. Here we describe the first case of cure of Hepatitis Delta following 3 years of Bulevirtide monotherapy in a patient with compensated cirrhosis and esophageal varices. During the 72-week off-Bulevirtide follow-up, virological and biochemical responses were maintained. In the off-therapy liver biopsy, intrahepatic HDV RNA and Hepatitis D antigen were undetectable, <1% hepatocytes were Hepatitis B surface antigen positive while hepatitis B core antigen was negative. Grading and staging improved compared to pre-treatment biopsy., (Copyright © 2022. Published by Elsevier B.V.)

Published
2023
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39. Bulevirtide monotherapy for 48 weeks in patients with HDV-related compensated cirrhosis and clinically significant portal hypertension.

Author

Degasperi E, Anolli MP, Uceda Renteria SC, Sambarino D, Borghi M, Perbellini R, Scholtes C, Facchetti F, Loglio A, Monico S, Fraquelli M, Costantino A, Ceriotti F, Zoulim F, and Lampertico P

Subjects
Aged, Female, Humans, Male, Middle Aged, Hepatitis Delta Virus genetics, Liver Cirrhosis complications, Liver Cirrhosis drug therapy, Adult, Antiviral Agents therapeutic use, Hepatitis D complications, Hepatitis D drug therapy, Hypertension, Portal complications, Hypertension, Portal drug therapy, Liver Neoplasms, Lipopeptides therapeutic use
Abstract

Background & Aims: Bulevirtide (BLV) has recently been conditionally approved for the treatment of chronic hepatitis delta (CHD) in Europe, but its effectiveness and safety in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH) are unknown., Methods: Consecutive patients with HDV-related compensated cirrhosis and CSPH who started BLV 2 mg/day were enrolled in this single-center study. Clinical/virological characteristics were collected at baseline, weeks 4, 8 and every 8 weeks thereafter. HDV RNA was quantified by Robogene 2.0 (lower limit of detection 6 IU/ml)., Results: Eighteen Caucasian patients with compensated cirrhosis and CSPH under nucleos(t)ide analogue treatment were enrolled: median (IQR) age was 48 (29-77) years, and 67% were male. Median (IQR) platelet count was 70 (37-227) x10 3 /μl, liver stiffness measurement (LSM) 16.4 (7.8-57.8) kPa, alanine aminotransferase (ALT) 106 (32-222) U/L, HBsAg 3.7 (2.5-4.3) log IU/ml, HDV RNA 4.9 (3.3-6.6) log IU/ml. During 48 weeks of BLV monotherapy, HDV RNA declined by 3.1 (0.2-4.3) log IU/ml (p <0.001 vs. baseline), becoming undetectable in 5 patients (23%). A virological response was observed in 14 (78%) patients while a non-response was observed in 2 (11%). ALT decreased to 35 (15-86) U/L (p <0.001 vs. baseline), normalizing in 83% of patients. A combined response was observed in 67% of patients. Aspartate aminotransferase and gamma-glutamyltransferase levels significantly improved. Concerning liver function parameters, albumin values significantly increased and bilirubin remained stable. LSM significantly improved in patients with virological response, while platelet count was unchanged. None of the patients developed decompensating events or hepatocellular carcinoma. BLV was well tolerated, no patient discontinued treatment and the increase in bile acids was fully asymptomatic., Conclusions: A 48-week course of BLV 2 mg/day monotherapy is safe and effective even for difficult-to treat patients with HDV-related compensated cirrhosis and CSPH., Lay Summary: Hepatitis delta virus (HDV) is associated with the most severe form of viral hepatitis. A new treatment for HDV called bulevirtide has recently received conditional approval for patients with chronic HDV infection. However, its safety and effectiveness in patients with more advanced liver disease is not known. Herein, we show that it is safe and effective in patients with HDV-related cirrhosis and clinically significant portal hypertension., Competing Interests: Conflict of interest Elisabetta Degasperi: Advisory Board: AbbVie; Speaking and teaching: Gilead, MSD, AbbVie; Alessandro Loglio: Travel grant for MYR Pharma, Speaker bureau for Gilead Sciences; Fabien Zoulim: Advisor for Aligos, Antios, Arbutus, Assembly, Gilead, GSK, MYR Pharma, Roche Pietro Lampertico: Advisor and speaker bureau for BMS, Roche, Gilead Sciences, GSK, MSD, Abbvie, Janssen, Arrowhead, Alnylam, Eiger, MYR Pharma, Antios, Aligos. Other authors have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2022
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40. [hPG 80 and cancer: A new blood biomarker in development for patient monitoring].

Author

You B, Assenat E, Payen L, Mazard T, Glehen O, Calattini S, Villeneuve L, Lescuyer G, Vire B, and Ychou M

Subjects
Biomarkers, Biomarkers, Tumor analysis, Humans, Monitoring, Physiologic, Neoplasm Recurrence, Local, Prognosis, Carcinoma, Hepatocellular genetics, Carcinoma, Renal Cell, Kidney Neoplasms, Liver Neoplasms diagnosis
Abstract

Recent technological advances coupled with our improved understanding of the molecular and cellular mechanisms associated with cancer development have enabled better overall patient care. Among the newly identified biomarkers such as circulating tumor DNA or circulating tumor cells, hPG 80 (circulating progastrin) that is easy to detect and quantify by a simple ELISA assay has the potential to become a new routine clinical tool in oncology if on-going studies validated its utility. Indeed, on the one hand, hPG 80 was found in the blood of patients with different tumors (colorectal, pancreatic, liver, lung, stomach, kidney cancers) at a significantly higher concentration than in healthy donors. Moreover, some studies suggested a potential association between hPG 80 concentration changes and anti-cancer treatment efficacy in patients with gastro-intestinal and hepatocellular carcinomas. Finally, hPG 80 might be a prognostic factor for overall survival in metastatic renal cell carcinoma cancer (mRCC) and in hepatocellular carcinoma (HCC). If these hypotheses were validated, hPG 80 might help better stratify patients according to their prognosis, and also become a tool to monitor relapse and predict treatment response. Prospective validation studies are on-going., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Published
2022
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41. Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort).

Author

Barré T, Fontaine H, Ramier C, Di Beo V, Pol S, Carrieri P, Marcellin F, Cagnot C, Dorival C, Zucman-Rossi J, Zoulim F, Carrat F, and Protopopescu C

Subjects
Aspartate Aminotransferases, Biomarkers, Coffee, Cross-Sectional Studies, Humans, Liver Cirrhosis complications, Platelet Count, Retrospective Studies, Severity of Illness Index, gamma-Glutamyltransferase, Hepatitis B, Chronic complications
Abstract

Background and Aims: Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients., Methods: Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status., Results: The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p ≤ 0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use., Conclusion: Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease., Competing Interests: Conflict of interest Stanislas Pol has served as a speaker, a consultant and an advisory board member for Janssen, Gilead, Roche, MSD, Abbvie, Biotest, Shinogi, Vivv, and LFB. He has received research funding from Gilead, Abbvie, Roche and MSD not connected to the present work. Fabrice Carrat reports grants from INSERM-ANRS during the implementation of this study and personal fees from Imaxio, outside the submitted work. The other authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Published
2022
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42. Clinical, radiological, and molecular diagnosis of congenital pituitary diseases causing short stature.

Author

Castets S, Villanueva C, Vergier J, Brue T, Saveanu A, and Reynaud R

Abstract

Short stature in children can be caused by congenital pituitary disorders involving at least one form of growth hormone deficiency. Clinical and radiological evaluations of the index case and family history assessments are essential to guide genetic diagnostic testing and interpret results. The first-line approach is panel testing of genes involved in pituitary development with variants known to be pathogenic in this context. It identifies a genetic cause in less than 10% of cases, however. Whole-exome and whole-genome sequencing techniques may provide original information but also raise new questions regarding the pathophysiological role of identified variants. These new tools can make genetic counselling more complex. The role of clinicians in these interpretations is therefore important. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved., (Copyright © French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Published
2022
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43. Covalently closed circular DNA: The ultimate therapeutic target for curing HBV infections.

Author

Martinez MG, Boyd A, Combe E, Testoni B, and Zoulim F

Subjects
Antiviral Agents pharmacology, Antiviral Agents therapeutic use, DNA, Circular therapeutic use, Hepatitis B virus genetics, Humans, Metal-Organic Frameworks pharmacology, Metal-Organic Frameworks therapeutic use, DNA, Circular pharmacology, Hepatitis B drug therapy
Abstract

Current antiviral therapies, such as pegylated interferon-α and nucleos(t)ide analogues, effectively improve the quality of life of patients with chronic hepatitis B. However, they can only control the infection rather than curing infected hepatocytes. Complete HBV cure is hampered by the lack of therapies that can directly affect the viral minichromosome (in the form of covalently closed circular DNA [cccDNA]). Approaches currently under investigation in early clinical trials are aimed at achieving a functional cure, defined as the loss of HBsAg and undetectable HBV DNA levels in serum. However, achieving a complete HBV cure requires therapies that can directly target the cccDNA pool, either via degradation, lethal mutations or functional silencing. In this review, we discuss cutting-edge technologies that could lead to non-cytolytic direct cccDNA targeting and cure of infected hepatocytes., Competing Interests: Conflict of interest BT and FZ declare a patent licensed by Hoffmann-La Roche. FZ received grants from Beam Therapeutics and Evotec paid to his institution. FZ received consulting fees from Aligos, Antios, Assembly Bioscience and Enochian. FZ received honoraria from Gilead and MYR Pharma as a consultant. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2021
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44. Full-length 5'RACE identifies all major HBV transcripts in HBV-infected hepatocytes and patient serum.

Author

Stadelmayer B, Diederichs A, Chapus F, Rivoire M, Neveu G, Alam A, Fraisse L, Carter K, Testoni B, and Zoulim F

Subjects
DNA, Viral analysis, Gene Expression Profiling methods, Humans, Transcriptome, Hepatitis B blood, Hepatitis B pathology, Hepatitis B virology, Hepatitis B virus genetics, Hepatitis B virus isolation & purification, Hepatocytes virology, Nucleic Acid Amplification Techniques methods
Abstract

Background & Aims: Covalently closed circular DNA (cccDNA) is the episomal form of the HBV genome that stably resides in the nucleus of infected hepatocytes. cccDNA is the template for the transcription of 6 major viral RNAs, i.e. preC, pg, preS1/2, S and HBx RNA. All viral transcripts share the same 3' end and are all to various degrees subsets of each other. Especially under infection conditions, it has been difficult to study in depth the transcription of the different viral transcripts. We thus wanted to develop a method with which we could easily detect the full spectrum of viral RNAs in any lab., Methods: We set up an HBV full-length 5'RACE (rapid amplification of cDNA ends) method with which we measured and characterized the full spectrum of viral RNAs in cell culture and in chronically infected patients., Results: In addition to canonical HBx transcripts coding for full-length X, we identified shorter HBx transcripts potentially coding for short X proteins. We showed that interferon-β treatment leads to a strong reduction of preC and pgRNAs but has only a moderate effect on the other viral transcripts. We found pgRNA, 1 spliced pgRNA variant and a variety of HBx transcripts associated with viral particles generated by HepAD38 cells. The different HBx RNAs are both capped and uncapped. Lastly, we identified 3 major categories of circulating RNA species in patients with chronic HBV infection: pgRNA, spliced pgRNA variants and HBx., Conclusions: This HBV full-length 5'RACE method should significantly contribute to the understanding of HBV transcription during the course of infection and therapy and may guide the development of novel therapies aimed at targeting cccDNA., Lay Summary: Especially under infection conditions, it has been difficult to study the different hepatitis B virus transcripts in depth. This study introduces a new method that can be used in any standard lab to discriminate all hepatitis B viral transcripts in cell culture and in the serum of patients., Competing Interests: Conflict of interest This work was part of a collaborative research agreement between INSERM and Evotec. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2020
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45. Recommendations for the use of electroencephalography and evoked potentials in comatose patients.

Author

André-Obadia N, Zyss J, Gavaret M, Lefaucheur JP, Azabou E, Boulogne S, Guérit JM, McGonigal A, Merle P, Mutschler V, Naccache L, Sabourdy C, Trébuchon A, Tyvaert L, Vercueil L, Rohaut B, and Delval A

Subjects
Brain physiopathology, Brain Waves, Humans, Coma diagnosis, Coma physiopathology, Electroencephalography, Evoked Potentials
Abstract

Predicting the outcome of a comatose or poorly responsive patient is a major issue for intensive care unit teams, in order to give the most accurate information to the family and to choose the best therapeutic option. However, determining the level of cortical activity in patients with disorders of consciousness is a real challenge. Reliable criteria are required to help clinicians in the decision-making process, especially in the acute phase of coma. In this paper, we propose recommendations for recording and interpreting electroencephalography and evoked potentials in comatose patients based on the literature and the clinical experience of a group of neurophysiologists trained in the management of comatose patients. We propose methodological guidelines and discuss prognostic value of each test as well as the limitations concerning recording and interpretation. Recommendations for the strategy and timing of neurophysiological assessments are also proposed according to various clinical situations., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Published
2018
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46. Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism.

Author

Niu C, Li L, Daffis S, Lucifora J, Bonnin M, Maadadi S, Salas E, Chu R, Ramos H, Livingston CM, Beran RK, Garg AV, Balsitis S, Durantel D, Zoulim F, Delaney WE 4th, and Fletcher SP

Subjects
Animals, Antigen Presentation, Cells, Cultured, Cytokines biosynthesis, DNA, Circular genetics, DNA, Circular metabolism, DNA, Viral genetics, DNA, Viral metabolism, Hepatitis B Antigens metabolism, Hepatitis B virus genetics, Hepatitis B virus immunology, Hepatitis B, Chronic drug therapy, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, Hepatocytes drug effects, Hepatocytes immunology, Hepatocytes virology, Humans, Immunity, Innate, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Viral genetics, RNA, Viral metabolism, Toll-Like Receptor 7 genetics, Antiviral Agents pharmacology, Hepatitis B virus drug effects, Interferon Type I immunology, Pteridines pharmacology, Toll-Like Receptor 7 agonists
Abstract

Background & Aims: GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection., Methods: Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined., Results: GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH., Conclusions: Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB., Lay Summary: GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic hepatitis B virus (HBV) infection. GS-9620 has previously been shown to suppress HBV in various animal models, but the underlying antiviral mechanisms were not completely understood. In this study, we determined that GS-9620 does not directly activate antiviral pathways in human liver cells, but can induce prolonged suppression of HBV via induction of an antiviral cytokine called interferon. However, interferon did not destroy the HBV genome, suggesting that other parts of the immune response (e.g. activation of immune cells that kill infected cells) also play an important role in the antiviral response to GS-9620., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2018
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47. The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals.

Author

Diab A, Foca A, Zoulim F, Durantel D, and Andrisani O

Subjects
Animals, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Drug Discovery, Gene Expression Regulation, Viral, Hepatitis B drug therapy, Hepatitis B Core Antigens chemistry, Hepatitis B Core Antigens genetics, Hepatitis B virus drug effects, Host-Pathogen Interactions, Humans, Phosphorylation, Protein Binding, Protein Transport, Viral Core Proteins antagonists & inhibitors, Viral Core Proteins chemistry, Viral Core Proteins genetics, Hepatitis B virology, Hepatitis B Core Antigens metabolism, Hepatitis B virus physiology, Viral Core Proteins metabolism
Abstract

Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis. In this article, we review the diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the unique structure of this protein is key to its various functions. We focus in particular on recent advances in understanding the significance of HBc phosphorylations, its interaction with host proteins and the role of HBc in regulating the transcription of host genes. We also briefly allude to the emerging niche for new direct-acting antivirals targeting HBc, known as Core (protein) Allosteric Modulators (CAMs)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2018
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48. Anatomy of lower eyelid and eyelid-cheek junction.

Author

Mojallal A and Cotofana S

Subjects
Humans, Cheek anatomy & histology, Eyelids anatomy & histology
Abstract

Background: Understanding the anatomy of the lower eyelid and the lid-cheek junction is important for surgical and non-surgical approaches. It is important to understand the correlation between the clinical presentation and the individual anatomy to direct an adequate treatment., Methods: A review of the literature based on the authors experience combined with anatomical dissections was conducted to reveal the current concepts of the surgical and non-surgical anatomy. The various anatomical structures important for the understanding of the symptoms and the proposed treatment are described in this article., Results: The anatomy of the lower eyelid and the lid-cheek junction has to be understood as a unit. Structures are continuous from the eyelid to the cheek influencing each other during aging. The concept of superficial, i.e. superficial to the orbicularis oculi muscle and deep facial fat compartments, i.e. deep to the orbicularis oculi muscle has to be applied in order to understand the relevant anatomy regarding the ligaments, fat compartments, muscular and tarsal structures and the vascularization., Conclusion: The understanding of the layered arrangement of the lower eyelid and eyelid-cheek junction anatomy enables practitioners to perform safe and effective surgical and non-surgical procedures., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Published
2017
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49. Detection of the hepatitis B virus (HBV) covalently-closed-circular DNA (cccDNA) in mice transduced with a recombinant AAV-HBV vector.

Author

Lucifora J, Salvetti A, Marniquet X, Mailly L, Testoni B, Fusil F, Inchauspé A, Michelet M, Michel ML, Levrero M, Cortez P, Baumert TF, Cosset FL, Challier C, Zoulim F, and Durantel D

Subjects
Animals, Blotting, Southern, DNA Replication, Disease Models, Animal, Hepatitis B drug therapy, Hepatocytes virology, Liver virology, Mice, Plasmids, Polymerase Chain Reaction methods, Transduction, Genetic, DNA, Circular isolation & purification, DNA, Viral isolation & purification, Dependovirus genetics, Genetic Vectors, Hepatitis B virology, Hepatitis B virus genetics
Abstract

Hepatitis B Virus (HBV) persists in infected hepatocytes as an episomal covalently-closed-circular DNA mini-chromosome, called cccDNA. As the main nuclear transcription template, HBV cccDNA is a key replication intermediate in the viral life cycle. Little is known about the mechanisms involved in its formation, maintenance and fate under antiviral therapies. This is mainly due to the lack of small immune-competent animal models able to recapitulate the entire HBV replication cycle, including formation of HBV cccDNA. Here we report that HBV cccDNA can be detected by Southern blot analyses in the liver of C57BL6 mice transduced with AAV-HBV. HBV cccDNA persists in the liver of these animals together with the AAV-HBV episome. We also set up a PCR strategy to distinguish the HBV cccDNA from the AAV-HBV episome. These suggest that the AAV-HBV/mouse model might be relevant to test drugs targeting HBV cccDNA regulation and persistence., (Copyright © 2017. Published by Elsevier B.V.)

Published
2017
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50. HDV RNA replication is associated with HBV repression and interferon-stimulated genes induction in super-infected hepatocytes.

Author

Alfaiate D, Lucifora J, Abeywickrama-Samarakoon N, Michelet M, Testoni B, Cortay JC, Sureau C, Zoulim F, Dény P, and Durantel D

Subjects
Cells, Cultured, Coinfection, DNA Replication, DNA, Circular, Hepatitis B virology, Hepatitis B e Antigens genetics, Hepatitis D virology, Hepatitis Delta Virus genetics, Humans, Interferon Type I immunology, Myxovirus Resistance Proteins genetics, Oxidoreductases Acting on CH-CH Group Donors, Proteins genetics, RNA, Viral biosynthesis, RNA, Viral genetics, Hepatitis B virus physiology, Hepatitis Delta Virus physiology, Hepatocytes virology, Immunity, Innate, Interferons immunology, Viral Interference, Virus Replication
Abstract

Hepatitis D virus (HDV) super-infection of Hepatitis B virus (HBV)-infected patients is the most aggressive form of viral hepatitis. HDV infection is not susceptible to direct anti-HBV drugs, and only suboptimal antiviral responses are obtained with interferon (IFN)-alpha-based therapy. To get insights on HDV replication and interplay with HBV in physiologically relevant hepatocytes, differentiated HepaRG (dHepaRG) cells, previously infected or not with HBV, were infected with HDV, and viral markers were extensively analyzed. Innate and IFN responses to HDV were monitored by measuring pro-inflammatory and interferon-stimulated gene (ISG) expression. Both mono- and super-infected dHepaRG cells supported a strong HDV intracellular replication, which was accompanied by a strong secretion of infectious HDV virions only in the super-infection setting and despite the low number of co-infected cells. Upon HDV super-infection, HBV replication markers including HBeAg, total HBV-DNA and pregenomic RNA were significantly decreased, confirming the interference of HDV on HBV. Yet, no decrease of circular covalently closed HBV DNA (cccDNA) and HBsAg levels was evidenced. At the peak of HDV-RNA accumulation and onset of interference on HBV replication, a strong type-I IFN response was observed, with interferon stimulated genes, RSAD2 (Viperin) and IFI78 (MxA) being highly induced. We established a cellular model to characterize in more detail the direct interference of HBV and HDV, and the indirect interplay between the two viruses via innate immune responses. This model will be instrumental to assess molecular and immunological mechanisms of this viral interference., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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