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1. First evidence of <scp> SOX2 </scp> mutations in Peters' anomaly: Lessons from molecular screening of 95 patients

Author: Bertrand Chesneau, Marion Aubert‐Mucca, Félix Fremont, Jacmine Pechmeja, Vincent Soler, Bertrand Isidor, Mathilde Nizon, Hélène Dollfus, Josseline Kaplan, Lucas Fares‐Taie, Jean‐Michel Rozet, Tiffany Busa, Didier Lacombe, Sophie Naudion, Jeanne Amiel, Marlène Rio, Tania Attie‐Bitach, Cécile Lesage, Dominique Thouvenin, Sylvie Odent, Godelieve Morel, Catherine Vincent‐Delorme, Odile Boute, Clémence Vanlerberghe, Anne Dieux, Simon Boussion, Laurence Faivre, Lucile Pinson, Fanny Laffargue, Gwenaël Le Guyader, Guylène Le Meur, Fabienne Prieur, Victor Lambert, Beatrice Laudier, Edouard Cottereau, Carmen Ayuso, Marta Corton‐Pérez, Laurence Bouneau, Cédric Le Caignec, Véronique Gaston, Claire Jeanton‐Scaramouche, Delphine Dupin‐Deguine, Patrick Calvas, Nicolas Chassaing, Julie Plaisancié, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Jeunes Aveugles [Toulouse] (IJA), Clinique rive gauche, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence Maladies Rares CLAD-Ouest [Rennes], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département génétique méd, mal rares et médecine personnalisée [CHRU de Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional d'Orléans (CHRO), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIBER de Enfermedades Raras (CIBERER), Universidad Autónoma de Madrid (UAM), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), French National Research AgencyFrench National Research Agency (ANR) [ANR-10-COHO-0003], and ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010)
Subjects: Comparative Genomic Hybridization, [SDV.GEN]Life Sciences [q-bio]/Genetics, DNA Copy Number Variations, SOXB1 Transcription Factors, Peters' anomaly, [SDV]Life Sciences [q-bio], CNV, SOX2, eye diseases, PAX6, Corneal Opacity, microphthalmia, Anterior Eye Segment, Mutation, B3GLCT, Genetics, Humans, anterior segment dysgenesis, FOXE3, Eye Abnormalities, PITX3, Genetics (clinical)
Abstract: International audience; Peters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development.
Published: 2022
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2. Characterization and multicentric validation of a common standard for Toxoplasma gondii detection using nucleic acid amplification assays

Author: Yvon Sterkers, Laurence Delhaes, Sophie Cassaing, Hervé Pelloux, Denis Filisetti, Emmanuelle Varlet-Marie, Feriel Touafek, Marie-Pierre Brenier-Pinchart, Hélène Yera, Patrick Bastien, Frédéric Dalle, Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de parasitologie-mycologie, CHU Grenoble, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Université de Bourgogne (UB), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de parasitologie et mycologie médicale [CHU Strasbourg], CHU Strasbourg, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de parasitologie-mycologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), We acknowledge the financial support of the 'RSI Assurance Maladie Professions Libérales—Provinces, C.A.M.P.L.P.' for buying the LightCycler 480 (Roche) real-time PCR equipment in Montpellier as well as that of the Institut de Veille Sanitaire (InVS)., We thank Florence Robert-Gangneux (CHU of Rennes) and Jean Menotti (Hôpital Saint-Louis, Paris) for fruitful discussions. We are grateful to Sylvie Matern and Rachel Huber (Strasbourg), Filomena Naji and Michèle Wauquier (Lille), Sylvie Douzou, Ghislaine Serres, and Bounleth Sanichanh (Montpellier), Catherine Barois (Grenoble), Anne Lamy, Raphaelle Laurenceau, Sandrine Chalmeton, Elodie Duthu, Séverine Gisquet, and Catherine Paris (Toulouse), and Cédric Rondot and Yacine Garaoun (Paris-Cochin) for technical assistance. We are indebted to Nathalie Van Langendonck (Academic Hospital of Tours) for providing AF samples. We are also grateful to Sebastien Besteiro (UMR CNRS 5235/University Montpellier 2, 'DIMNP') for providing the in vitro cultivated parasites., Pôle biologie Pathologie [CHRU Montpellier], Service de Parasitologie-Mycologie [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]
Subjects: Microbiology (medical), MESH: Reference Standards, MESH: Molecular Diagnostic Techniques/methods, MESH: Parasite Load/standards, [SDV]Life Sciences [q-bio], Toxoplasma gondii, diagnostic, Parasitic loads, Parasite Load, MESH: Nucleic Acid Amplification Techniques/standards, MESH: Toxoplasma/isolation & purification, medicine, Molecular diagnostic techniques, Humans, National level, Reference standards, MESH: Parasite Load/methods, standardization, MESH: Humans, biology, MESH: Nucleic Acid Amplification Techniques/methods, Nucleic acid amplification technique, MESH: Toxoplasmosis/diagnosis, MESH: Molecular Diagnostic Techniques/standards, Reference Standards, biology.organism_classification, medicine.disease, Virology, Toxoplasmosis, quantification, 3. Good health, MESH: France, Molecular Diagnostic Techniques, Immunology, Nucleic acid, MESH: Toxoplasma/genetics, Parasitology, France, Nucleic Acid Amplification Techniques, Toxoplasma
Abstract: The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community. High-quality written procedures were used for the production and qualification of this standard. Three independent batches of this standard, containing concentrations ranging from 10 4 to 0.01 T. gondii genome equivalents per PCR, were first assessed: the linear dynamic range was ≥6 log, the intra-assay coefficients of variation (CV) from a sample containing 10 T. gondii organisms per PCR were 0.3% to 0.42%, and the interassay CV over a 2-week period was 0.76% to 1.47%. A further assessment in eight diagnostic centers showed that the standard is stable, robust, and reliable. These lyophilized standards can easily be produced at a larger scale when needed and can be made widely available at the national level. To our knowledge, this is the first quality control assessment of a common standard which is usable both for self-evaluation in laboratories and for accurate quantification of parasitic loads in T. gondii prenatal infections.
Published: 2014
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3. Educational program in onco-urology for young urologists: What are their needs?

Author: Maxime Vallée, F. Bardet, N. Szabla, K. Kaulanjan, I. Dominique, T. Grevez, Clément Michiels, Lucas Freton, F. Lannes, E. Fortier, X. Matillon, Bastien Gondran-Tellier, Ugo Pinar, Zineddine Khene, M. Felber, Benjamin Pradere, E. Seizilles de Mazancourt, Groupe de Recherche Clinique Onco-Urologie Prédictive [CHU Tenon] (GRC 5), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Urologie Prado Louvain [Marseille], Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urologie [CHU Pitié-Salpêtrière], Département Pathologie et Onco-biologie [CHU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Urologie [CHU de Dijon], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hospices Civils de Lyon (HCL), Medizinische Universität Wien = Medical University of Vienna, and Gestionnaire, HAL Sorbonne Université 5
Subjects: Medical education, medicine.medical_specialty, Urologists, Urology, 030232 urology & nephrology, Formation médicale, Computer-assisted web interviewing, E-learning, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Digital media, Likert scale, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Surgical skills, Humans, Medicine, Social media, Internet, Internes, business.industry, Residents, Podcast, 4. Education, Internship and Residency, Evidence-based medicine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Onco-urologie, Surgical education, business, Educational program
Abstract: PurposeThe emergence of new communication media such as digital contents are progressively replacing more traditional medias in the field of educational programs. Our purpose was to assess urologist in training aspirations regarding urological education.MethodsMembers of a national urologist in training association were sent an anonymous online questionnaire regarding their medical formation in the field of urology. Responders interest for urological sub-specialty or education support (new tools and traditional support) were evaluated through a 5-point Likert scale.ResultsOverall, 109 young urologists (26%) responded to the survey. Most of the respondents worked during their training in an academic hospital (n = 89, 82%). The three favorite tools for training chosen by the responders were: videos, workshop or masterclass, and podcasts (responders very interested were respectively n = 64 (58.7%), n = 50 (45.9%), and n = 49 (45%)). E-mail newsletters were reported as the less useful educational tool by participants (n = 38, 34.9%). Participants were very interested in improving their surgical skills and their radiological knowledge. Responders who were the most attracted by PCa were much more looking to improve their systemic treatment and radiological knowledges.ConclusionsUrologic-oncology was a priority regarding education for urologists in training. A majority of participants expressed a lack in their surgical education, revealing a reduced OR access and underlining utilization of new tools such as simulation. New digital contents such as social media or podcast achieved high interest for the participants, instead of more traditional media. There is a need that educational content evolve and uses new digital media., ButDans la formation médicale, les nouveaux médias de communication tels que les contenus numériques se développent très rapidement et tendent à remplacer les médias plus traditionnels. Notre objectif était d’évaluer les aspirations des urologues en matière de formation en onco-urologie.MatérielLes membres de l’Associations française des urologues en formation ont répondu à un questionnaire en ligne anonyme concernant leur formation en onco-urologie. L’intérêt des participants pour les différents moyens de formation ainsi que pour les spécialités d’organes ont été évalués avec une échelle de Likert à 5-points.RésultatsAu total, 109 urologues en formation ont répondu à l’enquête (26 %). La plupart ont effectué leur formation exclusivement dans un hôpital universitaire (n = 89, 82 %). Les trois outils de formation préférés des participants étaient : les supports vidéo, les ateliers ou masterclass, et les podcast (étaient très intéressés respectivement n = 64 (59 %), n = 50 (46 %) et n = 49 (45 %)). Les newsletters ont été considérées comme l’outil éducatif le moins utile (n = 39, 35 %). Les participants étaient très intéressés par l’amélioration de leurs compétences chirurgicales et de leurs connaissances radiologiques. Les participants qui s’intéressaient le plus au cancer de la prostate cherchaient à consolider leurs connaissances sur les traitements systémiques ainsi qu’en radiologie.ConclusionL’onco-urologie est une priorité pour les urologues en formation. Les nouveaux contenus numériques tels que les réseaux sociaux ou les podcasts ont suscité un grand intérêt chez les participants, supplantant les médias plus traditionnels. Il est nécessaire que le contenu éducatif évolue et se repose sur les nouveaux médias numériques.
Published: 2021
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4. Evaluation of post-infectious inflammatory reactions in a retrospective study of 3 common invasive bacterial infections in pediatrics

Author: Pauline Abraham, Gregory Marin, Anne Filleron, Anne-Laure Michon, Hélène Marchandin, Sylvain Godreuil, Michel Rodière, Guillaume Sarrabay, Isabelle Touitou, Pauline Meslin, Carine Tournier, Philippe Van de Perre, Nicolas Nagot, Eric Jeziorski, Hôpitaux du Bassin de Thau, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Département de Bactériologie-Virologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Saint Jean de Perpignan, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)
Subjects: Fever, Streptococcus pyogenes, Communicable Diseases, MESH: Child, preschool, MESH: Streptococcal Infections, Streptococcal Infections, MESH: C-Reactive Protein, Humans, Child, Retrospective Studies, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Bacterial Infections / drug therapy, MESH: Fever / epidemiology, Infant, MESH: Retrospective Studies, General Medicine, Bacterial Infections, Anti-Bacterial Agents, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, C-Reactive Protein, Streptococcus pneumoniae, Child, Preschool, MESH: Communicable Diseases / drug therapy, MESH: Anti-Bacterial Agents / therapeutic use, MESH: Streptococcus pyogenes, MESH: Streptococcus pneumoniae
Abstract: International audience; Infectious diseases can result in unanticipated post-infectious inflammatory reactions (PIIR). Our aim was to explore PIIR in 3 frequent pediatric bacterial invasive infections in France by a retrospective monocentric study. We included children hospitalized between 2003 and 2012 for Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), or Streptococcus pyogenes invasive infections. The PIIR had to have occurred between 3 and 15 days without fever despite an individually tailored antibiotic therapy. A descriptive analysis was carried out to determine PIIR risk factors. We included 189 patients, of whom 72, 79, and 38 exhibited invasive infections caused by S pyogenes, SP, and NM, respectively. The mean age was 44 months. PIIR were observed in 39 cases, occurring after a median of 8 days (5-12), with a median duration of 3 days (2-6). Fever, arthritis, and pleural effusion were observed in 87%, 28.2%, and 25.6%, respectively. In multivariate analysis, PIIR were associated with pleuropneumonia, hospitalization in an intensive care unit (ICU), and elevated C-reactive protein (CRP). PIIR were observed in 20% of children after SP, NM, or S pyogenes invasives infections. Their occurrence was associated with the initial severity but not the etiological microorganism. Further studies are warranted to confirm these findings.
Published: 2022
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5. Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study

Author: Jérémy T, Campillo, Céline, Eiden, Michel, Boussinesq, Sébastien D S, Pion, Jean-Luc, Faillie, Cédric B, Chesnais, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Hibade, Monique
Subjects: adverse drug reactions, levamisole, MESH: Humans, Databases, Factual, Drug-Related Side Effects and Adverse Reactions, MESH: Pharmacovigilance, [SDV]Life Sciences [q-bio], disproportionality, MESH: Adverse Drug Reaction Reporting Systems, MESH: Databases, Factual, MESH: Drug-Related Side Effects and Adverse Reactions, [SDV] Life Sciences [q-bio], MESH: Levamisole, pharmacovigilance, Adverse Drug Reaction Reporting Systems, Humans
Abstract: Levamisole was initially prescribed for the treatment of intestinal worms. Because of immunomodulatory properties, levamisole has been used in inflammatory pathologies and in cancers in association with 5-fluorouracil. Levamisole is misused as a cocaine adulterant. Post-marketing reports have implicated levamisole in the occurrence of adverse drug reactions (ADRs) and its use is now limited in Europe and North America. In contrast, all other parts of the World continue to use single-dose levamisole as an anthelmintic. The aim of this study was to identify ADRs reported after levamisole exposure in VigiBase, the World Health Organisation's pharmacovigilance database, and analyse their frequency compared to other drugs and according to levamisole type of use.All levamisole-related ADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate psychiatric, hepatobiliary, renal, vascular, nervous, blood, skin, cardiac, musculoskeletal and general ADRs associated with levamisole and other drugs exposure. In secondary analyses, we compared the frequency of ADRs between levamisole and mebendazole and between levamisole type of use.Among the 1763 levamisole-related ADRs identified, psychiatric disorders (reporting odds ratio with 95% confidence intervals: 1.4 [1.2-2.6]), hepatobiliary disorders (2.4 [1.9-4.3]), vasculitis (6.5 [4.1-10.6]), encephalopathy (22.5 [17.4-39.9]), neuropathy (4.3 [2.9-7.1]), haematological disorders, mild rashes and musculoskeletal disorders were more frequently reported with levamisole than with other drug. The majority of levamisole-related ADRs occurred when the drug was administrated for a non-anti-infectious indication.The great majority of the levamisole-related ADRs concerned its immunomodulatory indication and multiple-dose regimen. Our results suggest that single-dose treatments for anthelmintic action have a good safety profile.
Published: 2022
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6. Diabetes and COVID-19

Author: Jean-Luc Cracowski, Jean-Luc Faillie, Béatrice Bouhanick, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Salvy-Córdoba, Nathalie
Subjects: Glucose control, MESH: Coronavirus Infections, Epidemiology, medicine.medical_treatment, Recommendations, Severity of Illness Index, 030226 pharmacology & pharmacy, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Insulin, MESH: COVID-19, MESH: Animals, Pharmacology (medical), Letter to the Editor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Dipeptidyl-Peptidase IV Inhibitors, Diabetes, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diabetes drugs, Coronavirus Infections, diabète, MESH: Pandemics, medicine.medical_specialty, MESH: Diabetes Mellitus, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Context (language use), MESH: Insulin, inhibiteurs des DPP-4, Article, 03 medical and health sciences, MESH: Hypoglycemic Agents, MESH: Severity of Illness Index, DPP-4 inhibitors, Diabetes mellitus, Diabetes Mellitus, medicine, Animals, Humans, Hypoglycemic Agents, Mortality, recommandations, Risk factor, Intensive care medicine, Pandemics, Dipeptidyl-Peptidase IV Inhibitors, MESH: Humans, Clinical events, business.industry, COVID-19, medicine.disease, Harm, MESH: Pneumonia, Viral, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance., D’après les dernières analyses de cas notamment en Chine et en Italie, le diabète semble être un facteur de risque d’aggravation de l’état clinique d’un patient atteint par le COVID-19 mais est-il un facteur de susceptibilité ? Une analyse de la littérature à la date du 6 mai 2020 tente de répondre à la question. Les données concernant le type de traitement antidiabétique à utiliser dans ces circonstances et son impact éventuel sur l’état clinique d’un patient infecté par le COVID-19 sont très rares. La dipeptidylpeptidase 4 (DPP-4), glycoprotéine membranaire ubiquitaire présente à la surface de nombreuses cellules et existant aussi sous forme soluble, est impliquée dans les réponses immunitaires inflammatoires en modifiant la production de plusieurs cytokines. La DPP-4 est impliquée dans l'infection des cellules par certains virus. Nous abordons la question de l’utilisation des inhibiteurs des DPP-4 chez les patients diabétiques et il n’y a pas à ce jour de données qui indiquent que l’état clinique des patients dépend de leur utilisation. De la même façon, l’utilisation de la metformine, des sulfamides hypoglycémiants, des analogues du GLP1 comme de l’insuline n’ont pas fait l’objet d’études dans ce contexte. Il nous parait prudent en phase aigüe de la maladie, en particulier chez les patients nécessitant un séjour en unités de soins intensifs de privilégier l’insuline chez eux. A la lumière d’une revue des recommandations sur la prise en charge des diabétiques,l’optimisation du contrôle glycémique est à privilégier et plusieurs messages clefs délivrés par les Sociétés savantes concluent ce travail.
Published: 2020
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7. COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave

Author: Bretagne, Stéphane, Sitbon, Karine, Botterel, Françoise, Dellière, Sarah, Letscher-Bru, Valérie, Chouaki, Taieb, Bellanger, Anne-Pauline, Bonnal, Christine, Fekkar, Arnault, Persat, Florence, Costa, Damien, Bourgeois, Nathalie, Dalle, Frédéric, Lussac-Sorton, Florian, Paugam, André, Cassaing, Sophie, Hasseine, Lilia, Huguenin, Antoine, Guennouni, Nadia, Mazars, Edith, Le Gal, Solène, Sasso, Milène, Brun, Sophie, Cadot, Lucile, Cassagne, Carole, Cateau, Estelle, Gangneux, Jean-Pierre, Moniot, Maxime, Roux, Anne-Laure, Tournus, Céline, Desbois-Nogard, Nicole, Le Coustumier, Alain, Moquet, Olivier, Alanio, Alexandre, Dromer, Françoise, Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive, modélisation et santé (GEMS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, CHU Henri Mondor [Créteil], Laboratoire de Parasitologie et de Mycologie Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie médicale [Hôpital de la Croix Rousse, Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Rouen, Normandie Université (NU), Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire de Parasitologie-Mycologie, Nice, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Centre hospitalier [Valenciennes, Nord], Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Hôpital Raymond Poincaré [AP-HP], Hôpital Ambroise Paré [AP-HP], Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Centre Hospitalier de Beauvais, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The NRCMA is supported by Santé Publique France and Institut Pasteur, Institut Pasteur [Paris], Génomique évolutive, modélisation et santé (CNRS-UMR2000), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), CHU Toulouse [Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Gestionnaire, Hal Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Henri Mondor, Laboratoire de parasitologie et mycologie médicale [CHU Strasbourg], CHU Strasbourg, Service de Parasitologie Mycologie[Bichat], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Subjects: Male, Antifungal Agents, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mannans, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19, aspergillosis, MESH: Treatment Outcome, MESH: Aged, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, fungemia, Coinfection, Pneumonia, Pneumocystis, Middle Aged, QR1-502, Intensive Care Units, Treatment Outcome, Aspergillus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, MESH: Pulmonary Aspergillosis, France, Research Article, MESH: Galactose, Microbiology, pneumocystosis, MESH: Mannans, MESH: Critical Care, MESH: Fungemia, Humans, MESH: SARS-CoV-2, Aged, Retrospective Studies, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, SARS-CoV-2, Galactose, COVID-19, MESH: Retrospective Studies, MESH: Antifungal Agents, MESH: Male, MESH: Coinfection, MESH: France, critical care, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pulmonary Aspergillosis, MESH: Female, MESH: Pneumonia, Pneumocystis
Abstract: International audience; The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (
Published: 2021
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8. Additive value of bioclinical risk scores to high sensitivity troponins-only strategy in acute coronary syndrome

Author: Louis Thiebaut, Jean-Paul Cristol, Grégoire Pasquier, Anne Marie Dupuy, Mustapha Sebbane, François Roubille, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], and MORNET, Dominique
Subjects: medicine.medical_specialty, Acute coronary syndrome, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Myocardial Infarction, 030204 cardiovascular system & hematology, Roche Diagnostics, Chest pain, Biochemistry, High sensitivity troponins, 03 medical and health sciences, 0302 clinical medicine, Troponin T, Risk Factors, Internal medicine, Humans, Medicine, In patient, Prospective Studies, 030212 general & internal medicine, cardiovascular diseases, Acute Coronary Syndrome, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Rule-out, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Bioclinical scores, biology, business.industry, Troponin I, Biochemistry (medical), General Medicine, Emergency department, medicine.disease, Troponin, 3. Good health, Heart score, biology.protein, medicine.symptom, Emergency Service, Hospital, business, Prediction, Biomarkers, TIMI
Abstract: International audience; Background: Discharging patients home as quickly as possible, or gaining the ability to eliminate a serious event is a goal requested by clinicians in the emergency department (ED). For this, risk scores, taking into account co-morbidities, have been established. The aim of our study consists to evaluate in patients with chest pain admitted in ED the risk stratification obtained with clinico-biological risk scores (CCS, GRACE score, TIMI score and HEART score) using Ortho hs-cTnI assay (Ortho Clinical Diagnostics, Illkirch, France) on the Vitros 3600® instrument or Roche hs-cTnT assay on the Cobas8000/e801® module (Roche diagnostics, Meylan, France), with comparison to hs-cTn-only strategy. Prognostic performances were evaluated according to AMI with or without STEMI, and deaths during hospitalization.Methods: Patients admitted to the ED presenting chest pain or symptoms suggesting of acute coronary syndrome (ACS) were included. Hs-cTnT was performed on a Roche hs-cTnT assay on the Cobas8000/e801® module using a fifth-generation assay and was used for the clinical diagnosis. In addition, hs-cTnI was tested using Ortho hs-cTnI assay on the Vitros 3600® analyzer. Retrospectively, we collected the variables needed for each score in clinical records. Our endpoint were occurrence of AMI in patients with chest pain after presentation to the ED and all cause death during the hospitalization.Results: We enrolled 160 patients with suspected ACS. The adjudicated diagnosis was AMI in 37 patients (with 9 STEMI and 28 NSTEMI), cardiac pathologies in 57 patients and other causes in 66 patients. The majority of patients were classified at high risk for each risk scores (from 42% to 68%) whatever the considered hs-cTn assay, except for TIMI score. Cohen's kappa agreements with GRACE, TIMI and HEART scores were excellent between Roche hs-cTnT vs Ortho hs-cTnI. The AUC of the HEART score was highest for both hs-cTn to predict AMI, NSTEMI or death, with no statistical difference according to the hs-cTn (p = NS) assay used. NRI analysis confirmed the interest of HEART score which improved individual risk prediction for AMI (or NSTEMI) and death.Conclusion: In view of our results, the decision aids using only biological variables (hs-cTn-only strategy and CCS) would seem more effective for rule-out AMI whereas bioclinical risk scores could better identify patients at low and high risk for mortality. In consequence, risk scores taking in account comorbidities, appear necessary to determine the outcome and thus to adapt the therapeutic options. It is interesting to note that the HEART score could be useful for the rule out AMI but also for the risk prediction as confirmed by the NRI.
Published: 2021
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9. The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias

Author: Rosa Paolillo, Mathias Boulanger, Pierre Gâtel, Ludovic Gabellier, Marion De Toledo, Denis Tempé, Rawan Hallal, Dana Akl, Jérôme Moreaux, Hayeon Baik, Elise Gueret, Christian Recher, Jean-Emmanuel Sarry, Guillaume Cartron, Marc Piechaczyk, Guillaume Bossis, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), bossis, guillaume, and 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)
Subjects: [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Drug Resistance, Neoplasm, [SDV]Life Sciences [q-bio], Daunorubicin, NADPH Oxidase 2, Humans, Hematology, Prognosis
Abstract: Resistance to chemotherapeutic drugs is a major cause of treatment failure in acute myeloid leukemias (AML). To better characterize the mechanisms of chemoresistance, we first identified genes whose expression is dysregulated in AML cells resistant to daunorubicin or cytarabine, the main drugs used for induction therapy. The genes found to be activated are mostly linked to immune signaling and inflammation. Among them, we identified a strong upregulation of the NOX2 NAPDH oxidase subunit genes (CYBB, CYBA, NCF1, NCF2, NCF4 and RAC2). The ensuing increase in NADPH oxidase expression and production of reactive oxygen species, which is particularly strong in daunorubicin-resistant cells, participates in the acquisition and/or maintenance of resistance to daunorubicin. Gp91phox (CYBB-encoded Nox2 catalytic subunit), was found to be more expressed and active in leukemic cells from patients with the French-American-British (FAB) M4/M5 subtypes of AML than in those from patients with the FAB M0-M2 ones. Moreover, its expression was increased at the surface of patients’ chemotherapy-resistant AML cells. Finally, using a gene expression based score we demonstrated that high expression of NOX2 subunit genes is a marker of adverse prognosis in AML patients. The prognostic NOX score we defined is independent of the cytogenetic-based risk classification, FAB subtype, FLT3/NPM1 mutational status and age.
Published: 2021
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10. Liquid biopsy and minimal residual disease — latest advances and implications for cure

Author: Klaus Pantel, Catherine Alix-Panabières, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Pôle Biologie-Pathologie [CHRU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Neoplasm, Residual, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Cell-Free Nucleic Acids/genetics, Neoplasm Residual/diagnosis, Neoplastic Cells, Circulating/pathology, Precision Medicine, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm, In patient, Liquid biopsy, business.industry, Liquid Biopsy, Cancer, Neoplastic Cells, Circulating, Prognosis, Primary lesion, medicine.disease, Precision medicine, Minimal residual disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, business, Cell-Free Nucleic Acids
Abstract: Liquid biopsy has been introduced as a new diagnostic concept predicated on the analysis of circulating tumour cells (CTCs) or circulating tumour-derived factors, in particular, cell-free tumour DNA (ctDNA). Highly sensitive liquid biopsy assays have been developed that can now be applied to detect and characterize minimal residual disease (MRD), which reflects the presence of tumour cells disseminated from the primary lesion to distant organs in patients who lack any clinical or radiological signs of metastasis or residual tumour cells left behind after local therapy that eventually lead to local recurrence. This application is the new frontier of liquid biopsy analyses, which are challenged by the very low concentrations of CTCs and ctDNA in blood samples. In this Review, we discuss the key technologies that can be used to detect and characterize CTCs in surveillance of MRD and provide a brief overview of similar roles of ctDNA analyses. We then focus on the current clinical data on the use of CTCs and ctDNA in the detection and monitoring of MRD and in obtaining information on therapeutic targets and resistance mechanisms relevant to the management of individual patients with cancer. In this Review, Pantel and Alix-Panabieres provide an overview of approaches for the detection and characterization of minimal residual disease (MRD) using circulating tumour cells and circulating tumour DNA. They also discuss the clinical implications of such liquid biopsy approaches to MRD monitoring for the management of patients with cancer.
Published: 2019
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11. High prevalence and characterization of extended-spectrum ß-lactamase producing Enterobacteriaceae in Chadian hospitals

Author: Ouchar Mahamat, Oumar, Lounnas, Manon, Hide, Mallorie, Dumont, Yann, Tidjani, Abelsalam, Kamougam, Kadidja, Abderrahmane, Madina, Benavides, Julio, Solassol, Jérôme, Bañuls, Anne-Laure, jean-Pierre, Hélène, Carrière, Christian, Godreuil, Sylvain, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Mère et de l’Enfant [N’Djaména, Tchad], Du gène à l'écosystème (MIVEGEC-GeneSys), Pathogènes, Environnement, Santé Humaine (EPATH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de N'Djaména, Hôpital Général des Références Nationale [N'Djamena, Tchad] (HGRN), L’hôpital de la Renaissance [D'Jamena, Tchad], Universidad Andrés Bello [Santiago] (UNAB), Pôle Biologie-Pathologie [CHRU Montpellier], Laboratoire Mixte International Drug Resistance in Southeast Asia (LMI DRISA), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU)-Fondation Mérieux-University of sciences and technologies of hanoi (USTH)-Center of Infectiology Lao-Christophe Mérieux [Vientiane] (CILM), This study was supported by a grant from Islamic Development Bank (IDB)., We would like to thank IRD and CHU. We thank Elisabetta Andermarcher for assistance in preparing and editing the manuscript., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU)-Fondation Mérieux-University of Science and Technology of Hanoi (USTH)-Center of Infectiology Lao-Christophe Mérieux [Vientiane] (CILM), Fondation Mérieux-Center of Infectiology Lao-Christophe Mérieux [Vientiane] (CILM)-Institut Pasteur du Cambodge, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-University of sciences and technologies of hanoi (USTH)-Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU)
Subjects: Male, Clinical samples, MESH: Chad/epidemiology, MESH: Anti-Bacterial Agents/pharmacology, MESH: Drug Resistance, Bacterial/genetics, MESH: Aged, 80 and over, MESH: Child, polycyclic compounds, Prevalence, Child, Aged, 80 and over, MESH: Aged, Cross Infection, MESH: Microbial Sensitivity Tests, MESH: Middle Aged, Enterobacteriaceae Infections, Middle Aged, MESH: Hospitals, Hospitals, MESH: Enterobacteriaceae Infections/epidemiology, Anti-Bacterial Agents, Child, Preschool, Female, MESH: Enterobacteriaceae Infections/microbiology, Research Article, Adult, Adolescent, Chad, MESH: Cross Infection/microbiology, Microbial Sensitivity Tests, beta-Lactamases, lcsh:Infectious and parasitic diseases, Enterobacteriaceae, Drug Resistance, Bacterial, MESH: Enterobacteriaceae/genetics, Humans, MESH: Drug Resistance, Bacterial/drug effects, lcsh:RC109-216, MESH: Enterobacteriaceae/pathogenicity, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, MESH: Child, Preschool, MESH: Adult, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, MESH: beta-Lactamases/genetics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, ESBL, MESH: Enterobacteriaceae/drug effects, bacteria, MESH: Female
Abstract: Background Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) represent a major problem in the management of nosocomial infections. However, ESBL-PE are not systematically monitored in African countries. The aim of this study was to determine ESBL-PE prevalence in patients from three hospitals in N’Djamena, the capital city of Chad, and to characterize the genetic origin of the observed resistance. Methods From January to March 2017, 313 non-duplicate isolates were recovered from various clinical specimens obtained from 1713 patients in the three main hospitals of N’Djamena. Bacterial species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Susceptibility to 28 antibiotics was tested using the disk diffusion method on Müller-Hinton agar, and ESBL production was confirmed with the double-disc synergy test. The most prevalent ESBL genes associated with the observed resistance were detected using multiplex PCR followed by double-stranded DNA sequencing. Results Among the 313 isolates, 197 belonged to the Enterobacteriaceae family. The overall ESBL-PE prevalence was 47.72% (n = 94/197), with a higher rate among inpatients compared with outpatients (54.13% vs. 34.37%). ESBL-PE prevalence was highest in older patients (≥60 years of age). E. coli was the most common ESBL-producer organism (63.8%), followed by K. pneumoniae (21.2%). ESBL-PE were mainly found in urine samples (75%). The CTX-M-1 group was dominant (96.7% of the 94 ESBL-PE isolates, CTX-M-15 enzyme), followed by the CTX-M-9 group (4.1%). 86% of resistant isolates harbored more than one ESBL-encoding gene. ESBL production was also associated with the highest levels of resistance to non-β-lactam drugs. Conclusions The prevalence of ESBL-PE harboring resistant genes encoding ESBLs of the CTX-M-1 group was high (48%) among clinical isolates of three main hospitals in Chad, suggesting an alarming spread of ESBL-PE among patients. Electronic supplementary material The online version of this article (10.1186/s12879-019-3838-1) contains supplementary material, which is available to authorized users.
Published: 2019
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12. Limitations of PCR detection of filarial DNA in human stools from subjects non-infected with soil-transmitted helminths

Author: Cédric B Chesnais, Maxime P M Doret, Narcisse Nzune-Toche, Michel Boussinesq, Joseph Kamgno, Sébastien D. S. Pion, Emmanuelle Varlet-Marie, Sabrina Locatelli, Hugues C. Nana-Djeunga, Salvy-Córdoba, Nathalie, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche sur les Filarioses et autres Maladies Tropicales - Centre for Research on Filariasis and other Tropical Diseases [Yaoundé] (CRFilMT), Département de Bactériologie-Virologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Infectious and parasitic diseases, RC109-216, Polymerase Chain Reaction, Soil, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, MESH: Helminths, mansonella perstans, MESH: Ascaris lumbricoides, 0303 health sciences, biology, Infectious Diseases, Trichuris, MESH: Trichuris, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, loa loa, [SDV.IB]Life Sciences [q-bio]/Bioengineering, stool sample, Ascaris lumbricoides, Loa loa, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Veterinary (miscellaneous), 030231 tropical medicine, Necator americanus, Filariasis, 03 medical and health sciences, MESH: Soil, pcr, Helminths, parasitic diseases, medicine, Animals, Humans, Mansonella perstans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, cameroon, Feces, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Humans, MESH: Polymerase Chain Reaction, biology.organism_classification, medicine.disease, Virology, Insect Science, Trichuris trichiura, Animal Science and Zoology, Parasitology
Abstract: The standard techniques for diagnosis of human filariasis are the microscopic examination of blood smears or skin biopsies, which are relatively invasive and poorly sensitive at low levels of infection. Recently, filarial DNA has been detected in fecal samples from non-human primates in Central Africa. The aim of this study was to demonstrate proof-of-concept of a non-invasive molecular diagnosis technique for human filariasis by targeting fragments of 12S rDNA, Cox1, ITS1 and LL20-15kDa ladder antigen-gene by conventional PCR in DNA extracted from stool samples of 52 people infected with Mansonella perstans and/or Loa loa . Of these, 10 patients were infected with soil-transmitted helminths ( Trichuris trichiura and/or Ascaris lumbricoides ), and none were positive for Necator americanus . Interestingly, no filarial gene fragments were detected in the stools of any of the 52 patients. Future studies should evaluate whether a co-infection with soil-transmitted helminths causing gastrointestinal bleeding and likely allowing (micro)filaria exit into the digestive tract, may facilitate the molecular detection of filarial DNA fragments in stool samples., Les techniques standards de diagnostic des filarioses humaines (examen microscopique de gouttes épaisses ou de biopsies cutanées) sont relativement invasives et peu sensibles à de faibles niveaux d’infection. De l’ADN de filaires a été récemment détecté dans des échantillons de fèces de primates non-humains en Afrique centrale. L’objectif de cette étude était de démontrer la preuve de concept d’un diagnostic moléculaire non invasif des filarioses chez l’homme en ciblant des fragments d’ADNr 12S, Cox1, ITS1 et l’antigène LL20-15kDa par PCR classique. L’ADN a été extrait d’échantillons de selles de 52 personnes infectées par Mansonella perstans et/ou Loa loa . Parmi ces patients, dix étaient infectés par des géohelminthes ( Trichuris trichiura et/ou Ascaris lumbricoides ) et aucun n’était positif pour Necator americanus . De manière intéressante, aucun fragment de gène de filaires n’a été détecté dans les selles des 52 patients. Des études futures devraient être menées pour évaluer si une coinfection avec des géohelminthes (provoquant des hémorragies gastro-intestinales et permettant probablement l’effraction de (micro)filaires dans le tube digestif) facilite la détection moléculaire de fragments d’ADN de filaires dans les selles.
Published: 2021
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13. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract: Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2021
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14. Health consequences of cocaine use in France: data from the French Addictovigilance Network

Author: EIDEN, C., VINCENT, M., SERRAND, C., SERRE, A., RICHARD, N., PICOT, M. C., FRAUGER, E., FOUILHE, N., DAVELUY, Amelie, PEYRIERE, H., FRENCH ADDICTOVIGILANCE, Network, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Grenoble, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'Évaluation et d'Information sur la Pharmacodépendance-Addictovigilance (CEIP de Marseille (PACA-Corse, Centre Associé)), Aix Marseille Université (AMU)-Faculté de Médecine [Marseille], Université de la Méditerranée - Aix-Marseille 2-Université de la Méditerranée - Aix-Marseille 2, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Cocaine use, Epidemiologic study, Complications, 030226 pharmacology & pharmacy, 03 medical and health sciences, Cocaine-Related Disorders, Pharmacovigilance, 0302 clinical medicine, Sex Factors, Medicine, Humans, Pharmacology (medical), Mortality, Crack cocaine, Cocaine powder, Pharmacology, Health consequences, Health professionals, business.industry, Mental Disorders, Pharmacoepidemiology, Age Factors, 3. Good health, Death, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Emergency medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, 030217 neurology & neurosurgery
Abstract: International audience; As the number and severity of complications related to cocaine use reported to the French Addictovigilance network have increased, the French health authorities requested a national epidemiologic study of the data collected by this network from 2010 to 2016. For this purpose, the spontaneous reports (SR) linked to cocaine notified by health professionals were analyzed as well as the data from the pharmacoepidemiological surveys OPPIDUM (Observational survey on illegal psychotropic substances or diverted from their clinical use) and DRAMES (Deaths related to the abuse of licit and illicit psychoactive substances). In total, 1,265 SRs were analyzed (510% increase from 2010 to 2016). Users were mainly men (952/1,261; 75%), with a median age of 35.0 years [IQ(25-75) : 28-42]. Cocaine was consumed through the intranasal route by 52% of users (416/797), followed by intravenous administration (32%, 253/797), and inhalation (24%, 190/797). The use of cocaine powder and crack-cocaine was reported in 70% (475/674) and 23% (154/674) of SRs, respectively. Cocaine was consumed with other psychoactive substances and alcohol in 47% (603/1265) and 60% (387/649) of cases, respectively. The main cocaine-related complications were psychiatric complications (29%), neurologic complications (24%), and cardiovascular complications (23%). Analysis of the OPPIDUM survey data showed that in 2016, 15.9% and 2.4% of the included subjects consumed cocaine or crack-cocaine the week preceding the survey, the highest rate for the 2006-2016 period. The DRAMES survey indicated that cocaine-related deaths increased by 3-fold from 2014 to 2016. These data confirm that cocaine use in France is worrying with an increase in the number of severe complications and deaths.
Published: 2020
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15. Synchronous primary neoplasia in patients with oropharyngeal cancer: Impact of tumor HPV status. A GETTEC multicentric study

Author: Florent Milliet, Emmanuel Chamorey, Guillaume Chambon, Laure Santini, Gilles Poissonnet, Alain Bizeau, Valérie Coste, Benjamin Lallemant, Olivier Dassonville, D. Culié, A. Modesto, Alexandre Bozec, H. Mirghani, Frederic Peyrade, Karen Benezery, Joanne Guerlain, Françoise Chapel, Thibault Galissier, Nicolas Fakhry, Agnès Dupret-Bories, Pascal Roger, Aicha Ben Lakdar, Anne Sophie Ramay, Julien Viotti, Renaud Garrel, Renaud Schiappa, Esma Saada-Bouzid, Florence Jourdan-Soulier, Stéphane Temam, Bruno Guelfucci, P. Gorphe, Anne Sudaka, Sébastien Vergez, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pôle Biologie-Pathologie [CHRU Montpellier], Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), 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), and Salvy-Córdoba, Nathalie
Subjects: Oncology, Male, Cancer Research, MESH: Chi-Square Distribution, Multivariate analysis, Lung Neoplasms, Esophageal Neoplasms, Oropharynx, MESH: Logistic Models, Logistic regression, Neoplasms, Multiple Primary, Tertiary Care Centers, Tumor Status, 0302 clinical medicine, MESH: Neoplasms, Multiple Primary, MESH: Incidence, 030223 otorhinolaryngology, Fisher's exact test, Cancer, MESH: Human papillomavirus 16, Univariate analysis, Human papillomavirus 16, MESH: Middle Aged, Incidence, Smoking, MESH: Confidence Intervals, Middle Aged, Oropharyngeal Neoplasms, MESH: Cyclin-Dependent Kinase Inhibitor p16, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, symbols, Female, France, Oral Surgery, Second primary neoplasia, MESH: Smoking, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human papilloma virus, 03 medical and health sciences, symbols.namesake, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Analysis of Variance, Internal medicine, medicine, Confidence Intervals, MESH: Squamous Cell Carcinoma of Head and Neck, Humans, Cyclin-Dependent Kinase Inhibitor p16, Retrospective Studies, MESH: Tertiary Care Centers, Analysis of Variance, MESH: Humans, Chi-Square Distribution, business.industry, Squamous Cell Carcinoma of Head and Neck, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, Comorbidity, MESH: Male, MESH: Lung Neoplasms, MESH: France, Logistic Models, MESH: Oropharyngeal Neoplasms, business, MESH: Female, MESH: Alcohol Drinking
Abstract: International audience; Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes.Material and methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models.Results: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN.Conclusion: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients.
Published: 2020
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16. Placenta-mediated complications: Nucleosomes and free DNA concentrations differ depending on subtypes

Author: Sylvie Bouvier, V. Letouzey, Mathieu Fortier, E. Nouvellon, Frédéric Grosjean, Christophe Demattei, Mathias Chea, Eric Mercier, E. Mousty, Jean-Christophe Gris, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pôle Biologie-Pathologie [CHRU Montpellier], 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 Sechenov First Moscow State Medical University
Subjects: Placenta, Intrauterine growth restriction, Physiology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030204 cardiovascular system & hematology, Preeclampsia, Cell-free DNA, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, Medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Hyper-coagulability, Fetus, Fetal Growth Retardation, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Hematology, DNA, medicine.disease, 3. Good health, Nucleosomes, Real-time polymerase chain reaction, medicine.anatomical_structure, Cell-free fetal DNA, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Complication, business
Abstract: International audience; Placenta-mediated pregnancy complications generate short- and long-term adverse medical outcomes for both the mother and the fetus. Nucleosomes and free DNA (fDNA) have been described in patients suffering from a wide range of inflammatory conditions.Objective: The objective of our study was to compare nucleosomes and fDNA circulating levels during pregnancy and particularly in women developing a placenta-mediated complication according to the subtype (preeclampsia or intrauterine growth restriction) (NCT01736826).Patients/methods: A total of 115 women were prospectively included in the study across three groups: 30 healthy non-pregnant women, 50 with normal pregnancy, and 35 with a complicated pregnancy. Blood samples were taken up to every 4 weeks for several women with normal pregnancy and nucleosomes and fDNA were quantified using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.Results: We show that nucleosomes and fDNA concentrations significantly increase during normal pregnancy, with concentrations at delivery differing between the two groups. Interestingly, we show that concentrations differ according to the type of placenta-mediated complications, with higher levels in preeclampsia compared to intrauterine growth restriction.Conclusions: These data suggest that nucleosomes and fDNA may be additional actors participating in placenta-mediated pregnancy complications.
Published: 2020
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17. Actualités du diagnostic des infections parasitaires et fongiques

Author: Florent Morio, Arezki Izri, Emilie Fréalle, Renaud Piarroux, Laurence Lachaud, Odile Villard, Stéphane Valot, Eric Dannaoui, Hélène Yera, Jean Menotti, Florence Persat, Sandrine Houzé, CHU Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Laboratoire de Parasitologie et de Mycologie Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), and Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)
Subjects: medicine.medical_specialty, Molecular biology, MESH: Parasitology, MESH: Mycology, Mycology, MESH: Parasitic Diseases, Serology, Fungal infections, MESH: Mycoses, MESH: Laboratories, Hospital, medicine, Humans, Medical physics, Diagnostic Techniques and Procedures, MESH: Diagnostic Techniques and Procedures, MESH: Humans, Mass spectrometry, business.industry, MESH: Clinical Laboratory Services, General Medicine, Clinical Laboratory Services, Laboratories, Hospital, Parasitic diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Mycoses, Parasitology, business
Abstract: International audience; The diagnosis of parasitic and fungal infections, historically based on the detection of these pathogens using direct diagnosis (macro/microscopic examination, culture) or serological methods, has considerably evolved in the last decades, especially with the development of molecular approaches and mass spectrometry. These techniques, as well as most analyses of parasitic and fungal serology, are mostly the preserve of Hospital University Centers Parasitology-Mycology laboratories. In 2016, the French association of medical parasitology and mycology teachers and hospital practitioners (Anofel) has provided a Catalogue of rare analyses, regularly updated and freely accessible on the Anofel website (https://anofel.net/). This tool, which hinges on 4 parts (parasitology, parasitic serology, mycology, and fungal serology), aims to provide information on all available analyses, and a list of hospital laboratories able to undertake them. It is complementary to the other reference works that were developed by our association, including the Guide of analyses and methods in parasitology and mycology, published in 2018, and the eANOFEL pictures and videos database, freely accessible online (http://www.eanofel.fr). In this article, we draw-up a state-of-the-art of the most specialized techniques available in the parasitology-mycology laboratories and presented in the Catalogue of rare analyses of the Anofel collegium, and their interest for the diagnosis of these infections.; Le diagnostic des infections parasitaires et fongiques, historiquement basé sur la détection de ces pathogènes par diagnostic direct (examen macro/microscopique, culture) ou sérologique, a connu durant les dernières décennies des évolutions importantes, avec notamment le développement d’approches moléculaires et de la spectrométrie de masse. Ces techniques, de même que la plupart des analyses en sérologie parasitaire et fongique, restent le plus souvent l’apanage des laboratoires de centres hospitaliers universitaires spécialisés en parasitologie-mycologie. En 2016, l’Association française des enseignants et praticiens hospitaliers titulaires de parasitologie et mycologie médicales (Anofel) a mis à disposition un Catalogue des analyses rares en accès libre sur le site d’Anofel (https://anofel.net/), et régulièrement mis à jour. Cet outil, qui s’articule en 4 volets (parasitologie, sérologie parasitaire, mycologie et sérologie fongique) a pour objectif de faciliter l’accès aux informations sur les analyses disponibles et les laboratoires hospitaliers capables de les prendre en charge. Il complète les autres ouvrages de référence élaborés par la collégiale Anofel, dont le Guide des analyses et méthodes en parasitologie et mycologie, publié en 2018, et la base de données d’images et de vidéos, en accès libre sur internet (http://www.eanofel.fr). L’objectif de cet article est de dresser un état des lieux des techniques plus spécialisées disponibles dans les laboratoires de parasitologie-mycologie, présentées dans le Catalogue des analyses rares de la collégiale Anofel, et leur intérêt pour le diagnostic de ces infections.
Published: 2020
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18. Rheumatic disorders associated with immune checkpoint inhibitors: what about myositis? An analysis of the WHO's adverse drug reactions database

Author: Thủy Nguyễn, Olivier Lambotte, P. Palassin, Xavier Quantin, Guillaume Taieb, P. Rullier, Chayma Ladhari, Philippe Guilpain, Xavier Ayrignac, Dominique Hillaire-Buys, Alexandre Thibault Jacques Maria, C. Lesage, Jean-Luc Faillie, Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 du Cancer de Montpellier (ICM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Salvy-Córdoba, Nathalie, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocarditis, Drug-Related Side Effects and Adverse Reactions, Combination therapy, Databases, Pharmaceutical, Epidemiology, Inflammatory arthritis, Autoimmune diseases, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, World Health Organization, Polymyositis, General Biochemistry, Genetics and Molecular Biology, Dermatomyositis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Pharmacovigilance, Case fatality rate, Humans, Immunology and Allergy, Medicine, Immune Checkpoint Inhibitors, Myositis, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: As shown by Kostine et al ,1 and recently underlined by Ceccarelli et al ,2 rheumatic inflammatory disorders induced by anticancer therapy are becoming a major concern for rheumatologists at the era of immune checkpoint inhibitors (ICIs). Beyond inflammatory arthritis, which may concern 10%–20% of patients, myositis represents a rare (
Published: 2020
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19. Next-generation sequencing and recombinant expression characterized aberrant splicing mechanisms and provided correction strategies in factor VII deficiency

Author: Delphine Buthiau, Paolo Ferraresi, Dario Balestra, Caroline Guittard, Roula Farah, Mirko Pinotti, Iva Maestri, Brigitte Pan-Petesh, Muriel Giansily-Blaizot, Università degli Studi di Ferrara (UniFE), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Saint George Hospital University Medical Center [Beirut, Lebanon]
Subjects: MESH: Mutation, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Factor VII Deficiency, RNA Splicing, 030204 cardiovascular system & hematology, Biology, Deep-intronic Mutation, Disorders of Coagulation and Fibrinolysis, FVII Deficiency, New Generation Sequencing, Splicing Correction, Article, DNA sequencing, NO, New Generation Sequencing, 03 medical and health sciences, Exon, chemistry.chemical_compound, 0302 clinical medicine, Humans, Allele, MESH: High-Throughput Nucleotide Sequencing, Gene, 030304 developmental biology, Genetics, 0303 health sciences, MESH: Humans, Factor VII, Homozygote, Haplotype, Coagulation & its Disorders, High-Throughput Nucleotide Sequencing, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Exons, Hematology, FVII Deficiency, Splicing Correction, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, chemistry, MESH: Factor VII Deficiency, Deep-intronic Mutation, Mutation, RNA splicing, MESH: Factor VII, Disorders of Coagulation and Fibrinolysis, MESH: Exons, MESH: RNA Splicing, MESH: Homozygote, Minigene
Abstract: International audience; Despite the exhaustive screening of F7 gene exons and exon-intron boundaries and promoter region, a significant proportion of mutated alleles remains unidentified in patients with coagulation factor VII deficiency. Here, we applied next-generation sequencing to 13 FVII-deficient patients displaying genotype-phenotype discrepancies upon conventional sequencing, and identified six rare intronic variants. Computational analysis predicted splicing effects for three of them, which would strengthen (c.571+78G>A; c.806-329G>A) or create (c.572-392C>G) intronic 5' splice sites (5'ss). In F7 minigene assays, the c.806-329G>A was ineffective while the c.571+78G>A change led to usage of the +79 cryptic 5'ss with only trace levels of correct transcripts (3% of wild-type), in accordance with factor VII activity levels in homozygotes (1-3% of normal). The c.572-392C>G change led to pseudo-exonization and frame-shift, but also substantial levels of correct transcripts (approx. 70%). However, this variant was associated with the common F7 polymorphic haplotype, predicted to further decrease factor VII levels; this provided some kind of explanation for the 10% factor VII levels in the homozygous patient. Intriguingly, the effect of the c.571+78G>A and c.572-392C>G changes, and particularly of the former (the most severe and well-represented in our cohort), was counteracted by antisense U7snRNA variants targeting the intronic 5'ss, thus demonstrating their pathogenic role. In conclusion, the combination of next-generation sequencing of the entire F7 gene with the minigene expression studies elucidated the molecular bases of factor VII deficiency in 10 of 13 patients, thus improving diagnosis and genetic counseling. It also provided a potential therapeutic approach based on antisense molecules that has been successfully exploited in other disorders.
Published: 2020
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20. Growth charts in Kabuki syndrome 1

Author: Claire Jeandel, Caroline Michot, Odile Boute, Mario Abaji, Stanislas Lyonnet, Julie Reversat, Lucile Pinson, Sandrine Akouete, Bertrand Isidor, Marie-Ange Delrue, Valérie Cormier-Daire, Isabelle Touitou, Pierre Sarda, Bérénice Doray, Tiffany Busa, Anne Moncla, Véra Georgescu, Alice Goldenberg, Damien Sanlaville, Cyril Amouroux, Elodie Sanchez, Mélanie Fradin, Guilaine Boursier, Didier Lacombe, Mouna Barat-Houari, Annick Toutain, Brigitte Gilbert-Dussardier, David Geneviève, Fabienne Giuliano, Kim Hanh Le Quan Sang, Joelle Roume, Marianne Till, Yves Alembick, Nicole Philip, Elise Schaefer, Marjolaine Willems, Claire Duflos, Aurélia Jacquette, Eudeline Alix, Sébastien Moutton, Adeline Bonnard, Vincent Gatinois, Marie-Pierre Cordier, Clarisse Baumann, Martine Le Merrer, Marie-Line Jacquemont, Lydie Burglen, Valentin Ruault, Laurence Faivre, Carole Corsini, Sylvie Manouvrier, Svetlana Gorokhova, Anna Pelet, Delphine Héron, Sylvie Odent, Jeanne Amiel, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'Information Médicale [CHRU Montpellier], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Robert Debré Paris, Hôpital Robert Debré, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique clinique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital saint Pierre, GH Sud Réunion, Centre de référence des maladies endocriniennes rares de la croissance et du développement [CHU Pitié-Salpêtrière], Département Pédiatrie [CHRU Montpellier], Pôle Femme Mère Enfant [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département génétique méd, mal rares et médecine personnalisée [CHRU de Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Salvy-Córdoba, Nathalie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
Subjects: Male, MESH: Neoplasm Proteins, CHILDREN, Growth, MESH: Growth Charts, Body Mass Index, MALFORMATION, Parental target size, MESH: Child, KDM6A, Growth Charts, Child, Specific curves, Genetics (clinical), 2. Zero hunger, Genetics & Heredity, Histone Demethylases, 0303 health sciences, education.field_of_study, 030305 genetics & heredity, Increase size, Circumference, MESH: Hematologic Diseases, Adult height, 3. Good health, Neoplasm Proteins, DNA-Binding Proteins, Vestibular Diseases, Child, Preschool, Cohort, MLL2, Female, MESH: Vestibular Diseases, Life Sciences & Biomedicine, MESH: Face, growth hormone deficiency, MESH: Abnormalities, Multiple, MESH: Mutation, Adolescent, growth, Population, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Growth hormone deficiency, MESH: Body Mass Index, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, EARS, MESH: Body Height, MESH: Histone Demethylases, Genetics, medicine, Humans, Abnormalities, Multiple, education, 030304 developmental biology, MESH: Adolescent, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, Kabuki syndrome, MESH: Humans, business.industry, MUTATIONS, Body Weight, MESH: Child, Preschool, specific curves, MAKE-UP-SYNDROME, medicine.disease, Hematologic Diseases, Body Height, MESH: Male, MESH: Body Weight, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, parental target size, Face, Mutation, business, Body mass index, MESH: Female, MESH: DNA-Binding Proteins, Demography
Abstract: Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: OMIM 300867) is caused by pathogenic variations in KMT2D or KDM6A. KS is characterized by multiple congenital anomalies and neurodevelopmental disorders. Growth restriction is frequently reported. Here we aimed to create specific growth charts for individuals with KS1, identify parameters used for size prognosis and investigate the impact of growth hormone therapy on adult height. Growth parameters and parental size were obtained for 95 KS1 individuals (41 females). Growth charts for height, weight, body mass index (BMI) and occipitofrontal circumference were generated in standard deviation values for the first time in KS1. Statural growth of KS1 individuals was compared to parental target size. According to the charts, height, weight, BMI, and occipitofrontal circumference were lower for KS1 individuals than the normative French population. For males and females, the mean growth of KS1 individuals was -2 and -1.8 SD of their parental target size, respectively. Growth hormone therapy did not increase size beyond the predicted size. This study, from the largest cohort available, proposes growth charts for widespread use in the management of KS1, especially for size prognosis and screening of other diseases responsible for growth impairment beyond a calculated specific target size. ispartof: AMERICAN JOURNAL OF MEDICAL GENETICS PART A vol:182 issue:3 pages:446-453 ispartof: location:United States status: published
Published: 2019
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21. Endoscopic subperichondrial transseptal transsphenoidal approach is safe and efficient for non-extended pituitary surgery

Author: Marine Le Corre, Isabelle Raingeard, F. Segnarbieux, Valentin Favier, Valérie Rigau, C. Cartier, Julien Boetto, Louis Crampette, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], and Pôle Biologie-Pathologie [CHRU Montpellier]
Subjects: Male, Mucous membrane of nose, 0302 clinical medicine, Medicine, 030223 otorhinolaryngology, Sinus (anatomy), MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Microadenoma, General Medicine, Middle Aged, Pituitary surgery, MESH: Sphenoid Sinus, 3. Good health, medicine.anatomical_structure, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, Neurosurgery, Adenoma, Adult, medicine.medical_specialty, Adolescent, Sphenoid Sinus, Perforation (oil well), MESH: Endoscopy, 03 medical and health sciences, Young Adult, Humans, Pituitary Neoplasms, Macroadenoma, MESH: Pituitary Neoplasms, Learning curve, Aged, Retrospective Studies, MESH: Adolescent, Surgical team, MESH: Adenoma, MESH: Humans, business.industry, Retrospective cohort study, Endonasal transsphenoidal surgery, MESH: Retrospective Studies, MESH: Adult, Endoscopy, medicine.disease, Endoscopic surgery, MESH: Male, Surgery, Otorhinolaryngology, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. Methods: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed.Results: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated.Conclusion: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.
Published: 2019
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22. Assessment of the first commercial multiplex PCR kit (ParaGENIE Crypto-Micro Real-Time PCR) for the detection of Cryptosporidium spp., Enterocytozoon bieneusi, and Encephalitozoon intestinalis from fecal samples

Author: M. Leterrier, Yohann Le Govic, Adrien Laude, Philippe Poirier, Marie Machouart, Patrice Le Pape, Nicolas Argy, Guillaume Desoubeaux, Frédéric Dalle, Jessica Beser, Nathalie Bourgeois, Rose-Anne Lavergne, Florent Morio, Estelle Cateau, Céline Nourrisson, Françoise Botterel, Stéphane Valot, Christelle Pomares, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Bio-Archéologie et d'Ecologie (CBAE), Université Montpellier 2 - Sciences et Techniques (UM2)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude des Interactions Hôte-Parasite (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de parasitologie mycologie (CHU de Dijon), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Public Health Agency of Sweden, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Laboratoire de Parasitologie-Mycologie (CHU de Clermont-Ferrand), CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de parasitologie, mycologie, médecine tropicale CHRU Bretonneau, Laboratoire de Parasitologie Mycologie (AP-HP, Hôpital Bichat), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Parasitologie-Mycologie [CHRU Nancy], Vin Aliment Microbiologie et Stress (VAlMiS), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Parasitologie-Mycologie (AP-HP Hôpital Henri Mondor), Hôpital Henri Mondor, Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Microbiologie (CHD de la Roche-Sur-Yon), CHD Vendee (La Roche Sur Yon), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Microbiology (medical), Enterocytozoon bieneusi, [SDV]Life Sciences [q-bio], 030106 microbiology, Cryptosporidium, Microsporidiosis, Cryptosporidium spp, Sensitivity and Specificity, Microbiology, law.invention, Encephalitozoon intestinalis, 03 medical and health sciences, Feces, 0302 clinical medicine, fluids and secretions, law, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Multiplex polymerase chain reaction, parasitic diseases, medicine, CE-IVD, Humans, 030212 general & internal medicine, DNA, Fungal, Polymerase chain reaction, ComputingMilieux_MISCELLANEOUS, Bacteriological Techniques, biology, Encephalitozoon, General Medicine, Multiplex PCR, DNA, Protozoan, Enterocytozoon, biology.organism_classification, medicine.disease, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, Stool, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Reagent Kits, Diagnostic, Multiplex Polymerase Chain Reaction
Abstract: International audience; Cryptosporidium spp. Enterocytozoon bieneusi and Encephalitozoon intestinalis are opportunistic pathogens responsible for gastrointestinal diseases. We evaluated the ParaGENIE Crypto-Micro Real-Time PCR kit (Ademtech, France), the first CE-IVD compliant PCR assay available for these pathogens. This study was conducted blindly against a reference panel of 115 stool specimens including positive samples for Cryptosporidium spp. (n = 48) and E. bieneusi (n = 38) as well as negative or positive samples for other parasites to test for cross-reactivity. An additional set of samples corresponding to 8 rare Cryptosporidium species was also included. Discrepancies were evaluated with external in-house PCR tests. The ParaGENIE Crypto-Micro PCR assay displayed a sensitivity/specificity of 91.7%/100% and 97.3%/98.7% for Cryptosporidium spp. and E. bieneusi, respectively, and was able to detect all 12 Cryptosporidium species of the reference panel, including rare species. This new CE-IVD assay will facilitate the diagnosis of intestinal cryptosporidiosis and microsporidiosis, a major concern in immunocompromised patients and travelers.
Published: 2019
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23. Case-non-case studies: Principle, methods, bias and interpretation

Author: Jean-Luc Faillie, Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Databases, Factual, Drug-Related Side Effects and Adverse Reactions, Computer science, Case–non-case studies, 030226 pharmacology & pharmacy, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Bias, medicine, Confidence Intervals, Odds Ratio, Adverse Drug Reaction Reporting Systems, Humans, Pharmacology (medical), Adverse effect, Disproportionality analysis, Interpretation (logic), Actuarial science, Modalities, Pharmacoepidemiology, Odds ratio, medicine.disease, Confidence interval, 3. Good health, Research Design, Reporting odds ratio, Data Interpretation, Statistical, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmaco epidemiologie, Adverse drug reaction
Abstract: International audience; Case-non-case studies are among the methods used to assess drug safety by analyzing the disproportionality of adverse drug reaction reports in pharmacovigilance databases. First used in the 1980s, the last few decades have seen a significant increase in the use of this study design. The principle of case-non-case studies is to compare the drug exposure of cases of an adverse reaction of interest with that of cases with other reported reactions and called "non-cases". Their results are presented in the form of reporting odds ratio (ROR), the interpretation of which makes it possible to highlight pharmacovigilance signals. This article describes the principle of case-non-case studies, the calculation method of the ROR and its confidence interval, the different analytical modalities and how to interpret its results with regard to the advantages and limitations of this type of study.
Published: 2019
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24. Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior

Author: Ariane Tempier, Valère Cacheux, Melissa Alame, Laura De Oliveira, Alicia Tourneret, Luc Durand, Vanessa Szablewski, Samia Gonzalez, Anna Gerbe, Valérie Costes-Martineau, Olivier Dereure, Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Hématologie biologique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and MEDIPATH
Subjects: 0301 basic medicine, Adult, Male, Skin Neoplasms, Anaplastic Lymphoma, CD30, Adolescent, Breast Implants, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Biology, Pathology and Forensic Medicine, Pathogenesis, STAT3, 03 medical and health sciences, Young Adult, 0302 clinical medicine, hemic and lymphatic diseases, Breast implant, PDL1, MESH: Biomarkers, Tumor / analysis, Lymphoma, Large-Cell, Anaplastic / etiology, Lymphoma, Large-Cell, Anaplastic / pathology, Skin Neoplasms / metabolism, Gene duplication, TP63, Biomarkers, Tumor, Humans, Child, Molecular Biology, Aged, Aged, 80 and over, GATA3, Cell Biology, General Medicine, Middle Aged, 030104 developmental biology, Cutaneous, 030220 oncology & carcinogenesis, Anaplastic lymphoma, Cancer research, Immunohistochemistry, Lymphoma, Large-Cell, Anaplastic, Female
Abstract: International audience; Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK-) show similar histopathological features including the presence of the "hallmark" cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK-, 13 PC-ALCL, and 2 BI-ALCL were included. Cases were tested for P53, P63, MUM1, MYC, GATA3, p-STAT3, PD1, and PDL1 protein expression and DUP22, TP53, TP63, MYC, and PDL1 chromosomal aberrations. As expected, S-ALCL ALK- patients had adverse outcome compare to PC and BI-ALCL. No difference was observed between the three groups concerning protein expression except for MUM1 that was significantly more frequently expressed in S-ALCL ALK- compared to PC-ALCL. In particular, constitutive activation of the STAT3 pathway and PDL1/PD1 immune-checkpoint expression was present in the three entities. TP53 deletion and PDL1 gene amplification were the commonest cytogenetic alterations and were present in the three entities. None of the studied biological parameters was associated with prognosis. Despite distinct clinical behavior, S-ALCL ALK-, PC-ALCL, and BI-ALCL share similar biological features. Larger series should be investigated with the current approach to determine more precisely the activity and the prognostic value of these biomarkers and pathways in each group.
Published: 2019
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25. C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection

Author: Valentin Goutaudier, Hélène Perrochia, Simon Mucha, Marie Bonnet, Sylvie Delmas, Florian Garo, Valérie Garrigue, Sébastien Lepreux, Vincent Pernin, Jean-Emmanuel Serre, Ilan Szwarc, Pierre Merville, Annie Ramounau-Pigot, Céline René, Jonathan Visentin, Bryan Paul Morgan, Véronique Frémeaux-Bacchi, Georges Mourad, Lionel Couzi, Moglie Le Quintrec, Salvy-Córdoba, Nathalie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
Subjects: 0301 basic medicine, Graft Rejection, Male, Pathology, Kidney Glomerulus, MESH: Graft Rejection / immunology, Kidney Glomerulus / immunology, Renal Artery / immunology, Retrospective Studies, Complement Membrane Attack Complex, Peritubular capillaries, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Renal Artery, Immunology and Allergy, complement, Complement Activation, Kidney transplantation, Original Research, Kidney, Glomerular basement membrane, Middle Aged, Allografts, C4d, 3. Good health, medicine.anatomical_structure, Kidney Tubules, antibody-mediated rejection, Immunohistochemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Kidney Diseases, lcsh:Immunologic diseases. Allergy, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, C5b9, Immunology, kidney transplantation, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Antibodies, 03 medical and health sciences, medicine, Humans, business.industry, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Staining, Complement system, Capillaries, Transplantation, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Allografts / immunotherapy, Antibodies / immunology, Capillaries / immunology, Complement Membrane Attack Complex / immunology, business, lcsh:RC581-607, 030215 immunology
Abstract: International audience; C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.
Published: 2018
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26. Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study

Author: Antonios Douros, Robert W. Platt, Hui Yin, François Montastruc, Jean-Luc Faillie, Oriana Hy Yu, Devin Abrahami, Nathaniel Bouganim, Laurent Azoulay, Centre for Clinical Epidemiology and Community Studies [Montreal, Canada] (CCECS), Jewish General Hospital, Department of Epidemiology, Biostatistics and Occupational Health [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Clinical Pharmacology and Toxicology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Division of Endocrinology [Montreal, QC, Canada], Département de Pharmacologie Médicale et de Toxicologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Oncology [Montréal], and Herrada, Anthony
Subjects: Male, medicine.medical_specialty, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Type 2 diabetes, Incretins, Glucagon-Like Peptide-1 Receptor, Cholangiocarcinoma, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Diabetes mellitus, Pharmacovigilance, Odds Ratio, Medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Aged, Proportional Hazards Models, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Proportional hazards model, Hazard ratio, General Medicine, Odds ratio, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Confidence interval, 3. Good health, Sulfonylurea Compounds, Bile Duct Neoplasms, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Thiazolidinediones, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cohort study
Abstract: ObjectiveTo determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.DesignPopulation based cohort study.SettingGeneral practices contributing data to the UK Clinical Practice Research Datalink.Participants154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018.Main outcome measuresUse of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization’s global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma.ResultsDuring 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively).ConclusionCompared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.
Published: 2018
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27. Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses

Author: Judith St-Onge, Anne-Laure Mosca-Boidron, Thibaud Jouan, Frédéric Tran-Mau-Them, Ange-Line Bruel, Laetitia Lambert, Sebastien Moutton, Aurélie Bourchany, Nolwenn Jean, Aurélia Jaquette, Christel Thauvin-Robinet, Daphné Lehalle, Elise Schaefer, Nada Houcinat, Charlotte Poe, Yannis Duffourd, Paul Kuentz, Salima El Chehadeh-Djebbar, Alice Masurel-Paulet, Martin Chevarin, Laurence Faivre, Sophie Nambot, Marjorie Willems, Mathilde Lefebvre, Nicole Laurent, Antonio Vitobello, Frédéric Huet, Julien Thevenon, Patrick Callier, Jean-Baptiste Rivière, Christophe Philippe, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), FHU TRANSLAD, Département de Génétique Clinique [CHRU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Génétique Médicale, Hôpital Civil, Strasbourg, Centre de Génétique (Hôpital de la Pitié-Salpétrière, Paris), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Service de Pathologie [CHU de Dijon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Département génétique méd, mal rares et médecine personnalisée [CHRU de Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Adult, Male, Exome sequencing, medicine.medical_specialty, Time Factors, Adolescent, Genetic counseling, Bioinformatics, Turnaround time, Sensitivity and Specificity, Undiagnosed genetic conditions, 03 medical and health sciences, Genetics, medicine, Humans, Exome, Genetic Testing, Medical diagnosis, Intensive care medicine, Child, Genetics (clinical), Genetic testing, Whole genome sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, medicine.diagnostic_test, business.industry, Infant, Newborn, Infant, General Medicine, Sequence Analysis, DNA, Diagnostic turnaround time, 3. Good health, Clinical trial, 030104 developmental biology, Early Diagnosis, Child, Preschool, Female, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: IF 2.137; International audience; BACKGROUND AND OBJECTIVE:Whole-exome sequencing (WES) has now entered medical practice with powerful applications in the diagnosis of rare Mendelian disorders. Although the usefulness and cost-effectiveness of WES have been widely demonstrated, it is essential to reduce the diagnostic turnaround time to make WES a first-line procedure. Since 2011, the automation of laboratory procedures and advances in sequencing chemistry have made it possible to carry out diagnostic whole genome sequencing from the blood sample to molecular diagnosis of suspected genetic disorders within 50 h. Taking advantage of these advances, the main objective of the study was to improve turnaround times for sequencing results.METHODS:WES was proposed to 29 patients with severe undiagnosed disorders with developmental abnormalities and faced with medical situations requiring rapid diagnosis. Each family gave consent. The extracted DNA was sequenced on a NextSeq500 (Illumina) instrument. Data were analyzed following standard procedures. Variants were interpreted using in-house software. Each rare variant affecting protein sequences with clinical relevance was tested for familial segregation.RESULTS:The diagnostic rate was 45% (13/29), with a mean turnaround time of 40 days from reception of the specimen to delivery of results to the referring physician. Besides permitting genetic counseling, the rapid diagnosis for positive families led to two pre-natal diagnoses and two inclusions in clinical trials.CONCLUSIONS:This pilot study demonstrated the feasibility of rapid diagnostic WES in our primary genetics center. It reduced the diagnostic odyssey and helped provide support to families.Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Published: 2017
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28. Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell

Author: Kassambara, A, Jourdan, M, Bruyer, A, Robert, N, Pantesco, V, Elemento, O, Klein, B, Moreaux, J, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Weill Medical College of Cornell University [New York], Université de Montpellier (UM), Larose, Catherine, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV]Life Sciences [q-bio], Plasma Cells, Computational Biology, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Repressor Proteins, MicroRNAs, Cell Transformation, Neoplastic, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Interferon Regulatory Factors, otorhinolaryngologic diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Gene Regulatory Networks, Positive Regulatory Domain I-Binding Factor 1, RNA, Messenger, Transcriptional Elongation Factors, Multiple Myeloma, ComputingMilieux_MISCELLANEOUS, Transcription Factors
Abstract: International audience; MicroRNAs (miRNAs) are small noncoding RNAs that attenuate expression of their mRNA targets. Here, we developed a new method and an R package, to easily infer candidate miRNA–mRNA target interactions that could be functional during a given biological process. Using this method, we described, for the first time, a comprehensive integrated analysis of miRNAs and mRNAs during human normal plasma cell differentiation (PCD). Our results reveal 63 miRNAs with significant temporal changes in their expression during normal PCD. We derived a high-confidence network of 295 target relationships comprising 47 miRNAs and 141 targets. These relationships include new examples of miRNAs that appear to coordinately regulate multiple members of critical pathways associated with PCD. Consistent with this, we have experimentally validated a role for the miRNA-30b/c/d-mediated regulation of key PCD factors (IRF4, PRDM1, ELL2 and ARID3A). Furthermore, we found that 24 PCD stage-specific miRNAs are aberrantly overexpressed in multiple myeloma (MM) tumor plasma cells compared to their normal counterpart, suggesting that MM cells frequently acquired expression changes in miRNAs already undergoing dynamic expression modulation during normal PCD. Altogether, our analysis identifies candidate novel key miRNAs regulating networks of significance for normal PCD and malignant plasma cell biology
Published: 2017
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29. Comparison of Leishmania killicki (syn. L. tropica) and Leishmania tropica Population Structure in Maghreb by Microsatellite Typing

Author: Jean-Pierre Dedet, Hamouda Babba, Patrick Lami, Najoua Haouas, Dhekra Chaara, Francine Pratlong, Anne-Laure Bañuls, Habib Mezhoud, Zoubir Harrat, Loïc Talignani, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Monastir - University of Monastir (UM), Centre National de Référence des Leishmanioses [CHRU Montpellier] (CNR-L), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Du gène à l'écosystème (MIVEGEC-GeneSys), Pathogènes, Environnement, Santé Humaine (EPATH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), University of Hail, Virostyle (MIVEGEC-Virostyle), Perturbations, Evolution, Virulence (PEV), Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur d'Algérie, Réseau International des Instituts Pasteur (RIIP), This study was funded by the Institut Français de Coopération de Tunisie fellowship for PhD students., We are grateful to Elisabetta Andermarcher for editing the English. We also thank Kaouther Jaouadi for the collection of some samples., and Université de Montpellier (UM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: MESH: Leishmaniasis, Cutaneous/transmission, Leishmania tropica, Genotyping Techniques, MESH: Leishmania/isolation & purification, MESH: Electrophoresis, Genetic analysis, 0302 clinical medicine, Africa, Northern, MESH: Animals, Phlebotomus, MESH: Genetic Variation, Ctenodactylus gundi, MESH: Genotype, Leishmania, Genetics, 0303 health sciences, education.field_of_study, biology, lcsh:Public aspects of medicine, MESH: Leishmania/genetics, Enzymes, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Rodentia/parasitology, MESH: Microsatellite Repeats, Microsatellite, Research Article, MESH: Enzymes/analysis, Electrophoresis, lcsh:Arctic medicine. Tropical medicine, Genotype, lcsh:RC955-962, 030231 tropical medicine, Population, MESH: Leishmaniasis, Cutaneous/epidemiology, Leishmaniasis, Cutaneous, Rodentia, MESH: Phlebotomus/parasitology, MESH: Disease Transmission, Infectious, 03 medical and health sciences, Spatio-Temporal Analysis, MESH: Spatio-Temporal Analysis, Cutaneous leishmaniasis, MESH: Genotyping Techniques, parasitic diseases, Disease Transmission, Infectious, medicine, Animals, Humans, education, 030304 developmental biology, MESH: Leishmaniasis, Cutaneous/parasitology, MESH: Humans, Public Health, Environmental and Occupational Health, Genetic Variation, MESH: Africa, Northern/epidemiology, lcsh:RA1-1270, medicine.disease, biology.organism_classification, MESH: Leishmania/classification, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Microsatellite Repeats
Abstract: Leishmania (L.) killicki (syn. L. tropica), which causes cutaneous leishmaniasis in Maghreb, was recently described in this region and identified as a subpopulation of L. tropica. The present genetic analysis was conducted to explore the spatio-temporal distribution of L. killicki (syn. L. tropica) and its transmission dynamics. To better understand the evolution of this parasite, its population structure was then compared with that of L. tropica populations from Morocco. In total 198 samples including 85 L. killicki (syn. L. tropica) (from Tunisia, Algeria and Libya) and 113 L. tropica specimens (all from Morocco) were tested. Theses samples were composed of 168 Leishmania strains isolated from human skin lesions, 27 DNA samples from human skin lesion biopsies, two DNA samples from Ctenodactylus gundi bone marrow and one DNA sample from a Phlebotomus sergenti female. The sample was analyzed by using MultiLocus Enzyme Electrophoresis (MLEE) and MultiLocus Microsatellite Typing (MLMT) approaches. Analysis of the MLMT data support the hypothesis that L. killicki (syn. L. tropica) belongs to the L. tropica complex, despite its strong genetic differentiation, and that it emerged from this taxon by a founder effect. Moreover, it revealed a strong structuring in L. killicki (syn. L. tropica) between Tunisia and Algeria and within the different Tunisian regions, suggesting low dispersion of L. killicki (syn. L. tropica) in space and time. Comparison of the L. tropica (exclusively from Morocco) and L. killicki (syn. L. tropica) population structures revealed distinct genetic organizations, reflecting different epidemiological cycles., Author Summary Leishmania killicki (syn. L. tropica) was discovered in 1986. Few studies have been conducted on this parasite exclusively described in Maghreb. Consequently, many elements on its epidemiology, transmission, population structure and dynamics remain unknown. To better understand the evolution of this parasite, its population structure has been compared with that of L. tropica populations from Morocco using Multilocus Enzyme Electrophoresis (MLEE) and MultiLocus Microsatellite Typing (MLMT) typing. MLMT data support the hypothesis that L. killicki (syn. L. tropica) belongs to the L. tropica complex despite the strong genetic differentiation between them. Despite the probable recent divergence between L. killicki (syn. L. tropica) and L. tropica, they seem to evolve differently. Indeed, L. killicki (syn. L. tropica) appears slightly polymorphic and highly structured in space and time, while L. tropica was genetically heterogeneous, slightly structured geographically and temporally. The different population structures revealed distinct genetic organizations, reflecting different epidemiological cycles. Several parameters could explain these opposite epidemiological and genetic patterns such as ecosystems, vectors and reservoirs.
Published: 2015
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30. Is real-time PCR-based diagnosis similar in performance to routine parasitological examination for the identification of Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica from stool samples? Evaluation of a new commercial multiplex PCR assay and literature review

Author: Estelle Cateau, M. Leterrier, Frédéric Dalle, Adrien Laude, Nicolas Argy, P. Le Pape, Céline Nourrisson, Y. Le Govic, Guillaume Desoubeaux, Marie Machouart, Françoise Botterel, Nathalie Bourgeois, Florent Morio, Stéphane Valot, Christelle Pomares, Laboratoire d'économie d'Orleans ( LEO ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Tours, Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Relations Hôte-Environnement ( RHEM ), Université Henri Poincaré - Nancy 1 ( UHP ), Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Anofel Cryptosporidium National Network, Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Ecologie et biologie des interactions ( EBI ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Regional Universitaire de Nantes, Géosciences Paris Sud ( GEOPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'économie d'Orleans (LEO), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Service des Recherches Métallurgiques Appliquées (SRMA), Département des Matériaux pour le Nucléaire (DMN), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Bactériologie-Hygiène, Géosciences Paris Sud (GEOPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Dijon, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie et Mycologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de parasitologie [Mondor], Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision (LAMSADE), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), L’UNAM Université, Groupe d’Etude des Interactions Hôte-Pathogène, UPRES EA 3142, CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction de l'Energie Nucléaire (CEA-DEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Statistique, Analyse et Modélisation Multidisciplinaire (SAmos-Marin Mersenne) (SAMM), Université Panthéon-Sorbonne (UP1), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)
Subjects: 0301 basic medicine, Microbiology (medical), 030231 tropical medicine, 030106 microbiology, Sensitivity and Specificity, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, 03 medical and health sciences, Entamoeba histolytica, Giardia intestinalis, Feces, 0302 clinical medicine, fluids and secretions, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Multiplex polymerase chain reaction, parasitic diseases, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Intestinal Diseases, Parasitic, stool, ComputingMilieux_MISCELLANEOUS, Cryptosporidium parvum, biology, [ SDV ] Life Sciences [q-bio], General Medicine, biology.organism_classification, DNA extraction, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Parasitology, Molecular Diagnostic Techniques, multiplex real-time PCR, microscopy, Giardia lamblia, Cryptosporidium hominis, Multiplex Polymerase Chain Reaction
Abstract: International audience; Microscopy is the reference standard for routine laboratory diagnosis in faecal parasitology but there is growing interest in alternative methods to overcome the limitations of microscopic examination, which is time-consuming and highly dependent on an operator's skills and expertise. Compared with microscopy, DNA detection by PCR is simple and can offer a better turnaround time. However, PCR performances remain difficult to assess as most studies have been conducted on a limited number of positive clinical samples and used in-house PCR methods. Our aim was to evaluate a new multiplex PCR assay (G-DiaParaTrio; Diagenode Diagnostics), targeting Giardia intestinalis, Cryptosporidium parvum/Cryptosporidium hominis and Entamoeba histolytica. To minimize the turnaround time, PCR was coupled with automated DNA extraction (QiaSymphony; Qiagen). The PCR assay was evaluated using a reference panel of 185 samples established by routine microscopic examination using a standardized protocol including Ziehl-Neelsen staining and adhesin detection by ELISA (E. histolytica II; TechLab). This panel, collected from 12 French parasitology laboratories, included 135 positive samples for G. intestinalis (n = 38), C. parvum/C. hominis (n = 26), E. histolytica (n = 5), 21 other gastrointestinal parasites, together with 50 negative samples. In all, the G-DiaParaTrio multiplex PCR assay identified 38 G. intestinalis, 25 C. parvum/C. hominis and five E. histolytica leading to sensitivity/specificity of 92%/100%, 96%/100% and 100%/100% for G. intestinalis, C. parvum/C. hominis and E. histolytica, respectively. This new multiplex PCR assay offers fast and reliable results, similar to microscopy-driven diagnosis for the detection of these gastrointestinal protozoa, allowing its implementation in routine clinical practice.
Published: 2015
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31. Montpellier Infectious Diseases -Pôle Rabelais (MID) 3rd annual meeting (2014)

Author: Matteo Bonazzi, Gaelle Lentini, Nathalie Chazal, Laurence Briant, Anne Blanc-Potard, Edouard Tuaillon, Sébastien Besteiro, Emmanuel Cornillot, Armen Sanosyan, Philippe Van de Perre, Roy Matkovic, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut de recherche en biothérapie, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Research groups, [SDV]Life Sciences [q-bio], Physiology, Library science, Translational research, Biology, Disease cluster, Communicable Diseases, Communicable Diseases, Emerging, Microbiology, Multidisciplinary approaches, Translational Research, Biomedical, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitic Diseases, Genetics, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Bacterial Infections, Congresses as Topic, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Virus Diseases, Drug Design, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectious diseases
Abstract: International audience; For the third time, teams belonging to the "Montpellier Infectious Diseases" network in the Rabelais BioHealth Cluster held their annual meeting on the 27th and 28th of November in Montpellier, France. While the 2012 meeting was focused on the cooperation between the local force tasks in biomedical and medical chemistry and presented the interdisciplinary research programs designed to fight against virus, bacteria and parasites, the 2014 edition of the meeting was focused on the translational research in infectious diseases and highlighted the bench-to-clinic strategies designed by academic and private research groups in the Montpellier area.
Published: 2015
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32. Molecular Diagnosis of Toxoplasmosis in Immunocompromised Patients: a 3-Year Multicenter Retrospective Study

Author: Jean Menotti, Laurence Delhaes, Frédéric Dalle, Patrick Bastien, Marie-Pierre Brenier-Pinchart, Hervé Pelloux, Emeline Scherer, Feriel Touafek, Emmanuelle Varlet-Marie, Isabelle Accoceberry, Sophie Cassaing, Julie Bonhomme, Christophe Hennequin, Hélène Yera, Denis Filisetti, Isabelle Villena, Yvon Sterkers, Florence Robert-Gangneux, Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Cochin [AP-HP], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Universitaire de Toulouse, Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Protozooses Transmises par l'Alimentation (Cryptosporidiose, Giardose et Toxoplasmose) : Mode de Contamination et Pathogénie (PROTAL) - EA 3800 (PROTAL), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de parasitologie et mycologie médicale [CHU Strasbourg], and CHU Strasbourg
Subjects: Microbiology (medical), Microbiological Techniques, medicine.medical_specialty, MESH: Molecular Diagnostic Techniques, Asymptomatic, Polymerase Chain Reaction, law.invention, Immunocompromised Host, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, medicine, MESH: Immunocompromised Host, Prevalence, Humans, ComputingMilieux_MISCELLANEOUS, Polymerase chain reaction, Immunodeficiency, Survival analysis, MESH: Prevalence, Retrospective Studies, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, business.industry, Incidence (epidemiology), MESH: Toxoplasma, MESH: Microbiological Techniques, Retrospective cohort study, MESH: Polymerase Chain Reaction, MESH: Retrospective Studies, medicine.disease, Survival Analysis, Toxoplasmosis, 3. Good health, Surgery, MESH: France, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Diagnostic Techniques, MESH: Survival Analysis, Chemoprophylaxis, MESH: Toxoplasmosis, Parasitology, France, medicine.symptom, business, Toxoplasma
Abstract: Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definitive diagnosis relies on parasite DNA detection, but little is known about the incidence and burden of disease in HIV-negative patients. A 3-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, in order to record the frequency of Toxoplasma gondii DNA detection in ICPs and to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, of 31,640 PCRs performed on samples from ICPs, 610 were positive (323 patients). Blood ( n = 337 samples), cerebrospinal fluid ( n = 101 samples), and aqueous humor ( n = 100 samples) were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV + ; the remaining 62% consisted of 72 HSCT, 14 solid organ transplant, and 26 miscellaneous immunodeficiency patients. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR result, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and they received specific treatment. Overall survival of allo-HSCT patients at 2 months was better in centers with PCR follow-up than in other centers ( P < 0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide preemptive treatment and improve outcome.
Published: 2015
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33. Mycobacterium bovis in Burkina Faso: Epidemiologic and Genetic Links between Human and Cattle Isolates

Author: Anne-Laure Bañuls, Antoinette Kaboré, Dorine Neveu, Zakaria Ganame, Estelle Kanyala, Sylvain Godreuil, Adjima Combary, Philippe Van de Perre, Nicolas Meda, Zekiba Tarnagda, Adama Sanou, Dezemon Zingue, Hervé Hien, Mathurin Dembélé, Moumini Nouctara, Centre Muraz [Bobo-Dioulasso, Burkina Faso], Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Université Joseph Ki-Zerbo [Ouagadougou] (UJZK), Département de Bactériologie-Virologie [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Du gène à l'écosystème (MIVEGEC-GeneSys), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Adult, Male, Veterinary medicine, lcsh:Arctic medicine. Tropical medicine, Genotype, lcsh:RC955-962, Prevalence, Minisatellite Repeats, Beef cattle, Microbiology, Genetic analysis, Mycobacterium tuberculosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Burkina Faso, parasitic diseases, Genetics, Animals, Humans, Typing, Molecular Biology, Genotyping, 2. Zero hunger, Mycobacterium bovis, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Genetic Variation, lcsh:RA1-1270, biology.organism_classification, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Genetic epidemiology, Cattle, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Research Article
Abstract: Background In sub-Saharan Africa, bovine tuberculosis (bTB) is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations. Methodology/principal findings Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5) or humans (1) or from both (1). Moreover, these data (genetic analyses and phenetic tree) showed that the M. bovis isolates belonged to the African 1 (Af1) clonal complex (81.8%) and the putative African 5 (Af5) clonal complex (18.2%), in agreement with the results of RDAf1 deletion typing. Conclusions/Significance This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso., Author Summary Bovine tuberculosis is an infectious disease caused by Mycobacterium bovis in livestock and wild animals. Humans can acquire this germ by aerogenous route when in close contact with infected animals, or by consuming unpasteurized dairy products from infected animals and also through the skin when handling infected carcasses. For the present study in Burkina Faso, M. bovis strains were collected from slaughtered animals during routine veterinarian inspection at the slaughterhouses of Bobo Dioulasso and Ouagadougou and also from patients with suspected pulmonary tuberculosis. The isolates were genetically characterized using three techniques: spoligotyping, MIRU-VNTR and RDAf1 deletion analysis. Our results highlight two aspects of M. bovis epidemiology that are crucial for disease control: i) M. bovis circulates between Burkina Faso and its neighbouring countries and ii) M. bovis is transmitted mainly between cattle, but also between cattle and humans, and potentially between humans. This study stresses the need to develop an efficient strategy to control M. bovis transmission, but also the difficulty to implement control measures because of the complex epidemiology of bovine tuberculosis in Burkina Faso.
Published: 2014
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34. Constitutive mosaic aneuploidy is a unique genetic feature widespread in the Leishmania genus

Author: Yvon Sterkers, Nathalie Bourgeois, Patrick Bastien, Lucien Crobu, Laurence Lachaud, Gilles Merlin, Nada Kuk, Christelle Morelle, Michel Pagès, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: Leishmania tropica, 030231 tropical medicine, Immunology, Leishmania donovani, Genetic exchange, Chromosome, Microbiology, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, Humans, Leishmania major, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In Situ Hybridization, Fluorescence, 030304 developmental biology, Genetics, Leishmania, 0303 health sciences, Genome, biology, Mosaicism, Strain (biology), biology.organism_classification, Aneuploidy, Infectious Diseases, Leishmania infantum, Ploidy, Genome, Protozoan
Abstract: Using fluorescence in situ hybridization, we determined the ploidy of four species of Leishmania: Leishmania infantum, Leishmania donovani, Leishmania tropica and Leishmania amazonensis. We found that each cell in a strain possesses a combination of mono-, di- and trisomies for all chromosomes; ploidy patterns were different among all strains/species. These results extend those we previously described in Leishmania major, demonstrating that mosaic aneuploidy is a genetic feature widespread to the Leishmania genus. In addition to the genetic consequences induced by this mosaicism, the apparent absence of alternation between haploid/diploid stages questions the modality of genetic exchange in Leishmania sp.
Published: 2014
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34 results on '"Pôle Biologie-Pathologie [CHRU Montpellier]"'

1. First evidence of <scp> SOX2 </scp> mutations in Peters' anomaly: Lessons from molecular screening of 95 patients

2. Characterization and multicentric validation of a common standard for Toxoplasma gondii detection using nucleic acid amplification assays

3. Educational program in onco-urology for young urologists: What are their needs?

4. Evaluation of post-infectious inflammatory reactions in a retrospective study of 3 common invasive bacterial infections in pediatrics

5. Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study

6. Diabetes and COVID-19

7. COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave

8. Additive value of bioclinical risk scores to high sensitivity troponins-only strategy in acute coronary syndrome

9. The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias

10. Liquid biopsy and minimal residual disease — latest advances and implications for cure

11. High prevalence and characterization of extended-spectrum ß-lactamase producing Enterobacteriaceae in Chadian hospitals

12. Limitations of PCR detection of filarial DNA in human stools from subjects non-infected with soil-transmitted helminths

13. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

14. Health consequences of cocaine use in France: data from the French Addictovigilance Network

15. Synchronous primary neoplasia in patients with oropharyngeal cancer: Impact of tumor HPV status. A GETTEC multicentric study

16. Placenta-mediated complications: Nucleosomes and free DNA concentrations differ depending on subtypes

17. Actualités du diagnostic des infections parasitaires et fongiques

18. Rheumatic disorders associated with immune checkpoint inhibitors: what about myositis? An analysis of the WHO's adverse drug reactions database

19. Next-generation sequencing and recombinant expression characterized aberrant splicing mechanisms and provided correction strategies in factor VII deficiency

20. Growth charts in Kabuki syndrome 1

21. Endoscopic subperichondrial transseptal transsphenoidal approach is safe and efficient for non-extended pituitary surgery

22. Assessment of the first commercial multiplex PCR kit (ParaGENIE Crypto-Micro Real-Time PCR) for the detection of Cryptosporidium spp., Enterocytozoon bieneusi, and Encephalitozoon intestinalis from fecal samples

23. Case-non-case studies: Principle, methods, bias and interpretation

24. Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior

25. C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection

26. Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study

27. Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses

28. Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell

29. Comparison of Leishmania killicki (syn. L. tropica) and Leishmania tropica Population Structure in Maghreb by Microsatellite Typing

31. Montpellier Infectious Diseases -Pôle Rabelais (MID) 3rd annual meeting (2014)

32. Molecular Diagnosis of Toxoplasmosis in Immunocompromised Patients: a 3-Year Multicenter Retrospective Study

33. Mycobacterium bovis in Burkina Faso: Epidemiologic and Genetic Links between Human and Cattle Isolates

34. Constitutive mosaic aneuploidy is a unique genetic feature widespread in the Leishmania genus

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34 results on '"Pôle Biologie-Pathologie [CHRU Montpellier]"'

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