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1. 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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2. EGFR-dependent mechanisms of resistance to osimertinib determined by ctDNA NGS analysis identify patients with better outcome

Author: Xavier Quantin, Jérôme Solassol, Isabelle Serre, Julie A. Vendrell, Audrey Aussel, Isabelle Solassol, 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), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), and Herrada, Anthony
Subjects: circulating tumor DNA, Oncology, medicine.medical_specialty, EGFR-TKI resistance, business.industry, clinical outcome, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Outcome (game theory), lung cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, osimertinib, Internal medicine, medicine, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Original Article, Osimertinib, Lung cancer, business
Abstract: International audience; Background: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is highly selective for EGFR T790M subclones in patients with EGFR sensitizing non-small cell lung cancer (NSCLC). Unfortunately, all patients develop resistance through EGFR-dependent or EGFR-independent pathways. Recently, circulating tumoral DNA (ctDNA) analysis has highlighted the usefulness of plasma genotyping for exploring patient survival outcomes after disease progression under osimertinib.Methods: Plasma samples from patients treated with osimertinib as a second-line therapy were collected and the presence of molecular alterations of acquired resistance was evaluated after relapse under osimertinib using ctDNA molecular profiling by next-generation sequencing (NGS) assays. The clinical implications of these genomic alterations for the efficiency of the third-generation TKI were further assessed.Results: Our ctDNA molecular profiling of plasma samples highlighted large number of actionable genomic alterations. According to ctDNA NGS results, patients were classified as having developed an EGFR-dependent or EGFR-independent mechanism of resistance. Thus, patients who developed an EGFR-dependent mechanism of resistance responded longer to osimertinib (13.8 vs. 4.6 months; P
Published: 2021
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3. 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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4. 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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5. 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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6. Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

Author: Arthur Dujardin, Arnaud de La Blanchardière, Julia Dina, Karl Stefic, Christophe Ravel, Julie Bonhomme, Renaud Verdon, Anna Lucie Fournier, Unité de Maladies Infectieuses et Tropicales [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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]), 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Immunology, Case Report, Serology, pancytopenia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, visceral leishmaniasis, Medical history, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Hemophagocytic lymphohistiocytosis, bone marrow aspirate, business.industry, HIV, RC581-607, medicine.disease, Pancytopenia, 3. Good health, Visceral leishmaniasis, medicine.anatomical_structure, hemophagocytic lymphohistiocytosis, Chills, Bone marrow, medicine.symptom, Immunologic diseases. Allergy, business, Viral load
Abstract: We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.
Published: 2021
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7. 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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8. 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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9. Proximal Protein Interaction Landscape of RAS Paralogs

Author: Etienne Coyaud, Muriel Le Romancer, Benoît Béganton, Jérôme Solassol, Julien Jacquemetton, Brian Raught, Alain Mangé, Estelle M.N. Laurent, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Department of Medical Biophysics (MBP), University of Toronto, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mangé, Alain, INSERM, Université de Lille, Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, and Centre Léon Bérard [Lyon]
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Cancer Research, Upstream and downstream (transduction), interactome, Computational biology, Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine.disease_cause, Interactome, Article, RAS paralogs, Protein–protein interaction, 03 medical and health sciences, 0302 clinical medicine, protein– RAS paralogs, BioID, protein interaction, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, HRAS, ComputingMilieux_MISCELLANEOUS, Wild type, Cancer, medicine.disease, protein–protein interaction, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, KRAS
Abstract: RAS proteins (KRAS, NRAS and HRAS) are frequently activated in different cancer types (e.g., non-small cell lung cancer, colorectal cancer, melanoma and bladder cancer). For many years, their activities were considered redundant due to their high degree of sequence homology (80% identity) and their shared upstream and downstream protein partners. However, the high conservation of the Hyper-Variable-Region across mammalian species, the preferential activation of different RAS proteins in specific tumor types and the specific post-translational modifications and plasma membrane-localization of each paralog suggest they could ensure discrete functions. To gain insights into RAS proteins specificities, we explored their proximal protein&ndash, protein interaction landscapes using the proximity-dependent biotin identification technology (BioID) in Flp-In T-REx 293 cell lines stably transfected and inducibly expressing wild type KRAS4B, NRAS or HRAS. We identified more than 800 high-confidence proximal interactors, allowing us to propose an unprecedented comparative analysis of wild type RAS paralogs protein networks. These data bring novel information on poorly characterized RAS functions, e.g., its putative involvement in metabolic pathways, and on shared as well as paralog-specific protein networks that could partially explain the complexity of RAS functions. These networks of protein interactions open numerous avenues to better understand RAS paralogs biological activities.
Published: 2020
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10. TERT Promoter Mutation as an Independent Prognostic Marker for Poor Prognosis MAPK Inhibitors-Treated Melanoma

Author: Jérôme Solassol, Géraldine Chauchard, Vincent Ducros, Pauline Blateau, Estelle M.N. Laurent, Benoît Béganton, Etienne Coyaud, Julie A. Vendrell, INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, 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), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SALZET, Michel, and Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, MAPK/ERK pathway, Cancer Research, BRAF V600, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], melanoma, Medicine, Clinical significance, prognosis factor, Protein kinase A, Genotyping, neoplasms, BRAFV600, Mutation, business.industry, Melanoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, targeted therapies, 3. Good health, 030104 developmental biology, Oncology, chemistry, TERT promoter, 030220 oncology & carcinogenesis, Cancer research, co-occurring mutation, business, Brain metastasis
Abstract: Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAFV600 cutaneous melanomas, the identification of molecular indicators for mutated patients at risk of early progression remains a major issue. Using an amplicon-based next-generation-sequencing (NGS) assay that targets cancer-related genes, we investigated co-occurring alterations in 89 melanoma samples. We analyzed both their association with clinicopathological variables and clinical significance in terms of progression-free survival (PFS) and overall survival (OS) according to BRAF genotyping. Among co-occurring mutations, TERT promoter was the most frequently mutated gene. Although no significant difference in PFS was observed in the presence or absence of co-occurring alterations to BRAFV600, there was a trend of longer PFS for patients harboring TERT c.-124C&gt, T mutation. Of most interest, this mutation is an independent marker of good prognosis in subgroups of patients with poor prognosis (presence of brain metastasis and elevated level of lactate dehydrogenase, LDH). Moreover, combination of elevated LDH level, presence of brain metastasis, and TERT c.-124C&gt, T mutation was identified as the best fit model for predicting clinical outcome. Our work revealed the potential interest of c.-124C&gt, T status determination in order to refine the prognosis of BRAFV600 melanoma under mitogen-activated protein kinase (MAPK) inhibitors.
Published: 2020
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11. 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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12. 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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13. 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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14. Primary Cutaneous Gamma-Delta T-cell Lymphoma: Not an Aggressive Disease in All Cases

Author: Florent Grange, Morgane Condamina, Vanessa Szablewski, Olivier Dereure, Bernard Guillot, Mehdi Khallaayoune, 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 ), Centre Hospitalier Universitaire de Reims (CHU Reims), Pôle Biologie-Pathologie [CHRU Montpellier], and Salvy-Córdoba, Nathalie
Subjects: Pathology, medicine.medical_specialty, MESH: Remission Induction, MESH: Fatal Outcome, [SDV.CAN]Life Sciences [q-bio]/Cancer, Aggressive disease, Dermatology, Malignancy, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Receptors, Antigen, T-Cell, gamma-delta, Primary cutaneous gamma-delta T-cell lymphoma, medicine, Indolent, MESH: Treatment Outcome, MESH: Aged, Gamma-delta T-cell lymphoma, Hardware_MEMORYSTRUCTURES, MESH: Humans, business.industry, MESH: Skin Neoplasms, Primary cutaneous lymphoma, General Medicine, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, MESH: Lymphoma, T-Cell, Cutaneous, MESH: Male, 3. Good health, Lymphoma, MESH: Antineoplastic Combined Chemotherapy Protocols, 030220 oncology & carcinogenesis, RL1-803, Primary cutaneous, MESH: Disease Progression, business, MESH: Female, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Primary cutaneous gamma-delta T-cell lymphoma (PCGDTCL) is a rare form of primary cutaneous lymphoma characterized by a clonal proliferation of mature γ/δ T lymphocytes. PCGDTCL is usually considered an aggressive and rapidly evolving malignancy. Contrasting with this patter, we hereby report 2 unusual cases with a protracted indolent evolution.
Published: 2020
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15. 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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16. 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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17. Anticorps anti-CD38 dans le myélome multiple

Author: Jérôme Moreaux, 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], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Programmed cell death, Phagocytosis, [SDV]Life Sciences [q-bio], CD38, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Medicine, Cytotoxicity, Multiple myeloma, Antibody-dependent cell-mediated cytotoxicity, biology, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, medicine.disease, 3. Good health, Cytolysis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Antibody, business, 030215 immunology
Abstract: International audience; The high CD38 expression by plasma cells together with the biological functions of CD38 resulted in the development of CD38 antibodies for the treatment of multiple myeloma (MM) patients. The cytolytic activity of CD38 antibodies is mediated by complement-dependent cytoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), direct cell death effects and immunomodulatory effects. CD38 antibodies have demonstrated their clinical benefit as single agent or in combination for the treatment of multiple myeloma patients and will contribute to further improvement in the outcome of MM patients.; La forte expression de la molécule CD38 par les cellules plasmocytaires ainsi que son rôle biologique dans la régulation de l’adhérence et la migration cellulaire, avec des fonctions de signalisation, a conduit au développement d’anticorps spécifiques pour le traitement de patients atteints de myélome multiple (MM). Ces anticorps induisent en effet la mort des cellules de myélome multiple par des mécanismes de lyse cellulaire dépendante du complément (CDC), de cytotoxicité cellulaire dépendante des anticorps (ADCC), de phagocytose cellulaire dépendant des anticorps (ADCP), mais aussi par des mécanismes directs d’induction de mort cellulaire. Ils ont de plus des effets immunomodulateurs liés à l’élimination de cellules immunitaires immunosuppressives qui expriment également CD38. Bien qu’ayant des actions variables par rapport à ce registre d’activité si on les compare entre eux, les anticorps anti-CD38 ont démontré une activité clinique significative, seuls ou en combinaison avec diverses molécules, chez les patients atteints de MM. Ils contribueront sans aucun doute à des progrès majeurs pour la prise en charge thérapeutique des patients atteints de MM.
Published: 2019
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18. 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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19. 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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20. 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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21. Composite cutaneous lymphoma of diffuse large B-cell lymphoma-leg type and subcutaneous panniculitis-like T-cell lymphoma

Author: Céline René, Vanessa Szablewski, Jean-Marie Joujoux, Valérie Costes-Martineau, Aurélie Croci-Torti, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pôle Biologie-Pathologie [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 ), 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Histology, Dermatology, Cutaneous lymphoma, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, composite lymphoma, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Gammopathy, hemic and lymphatic diseases, Biopsy, medicine, CD20, subcutaneous panniculitis-like T-cell lymphoma, medicine.diagnostic_test, biology, business.industry, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, 030220 oncology & carcinogenesis, primary cutaneous large B-cell lymphoma-leg type, biology.protein, business, Diffuse large B-cell lymphoma, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Composite lymphoma (CL) is a rare disease defined by the occurrence of two distinct lymphomas within a single tissue at the same time. We present the case of an 89-year-old male with a clinical history of immunoglobulin M monoclonal gammopathy of undetermined significance. The patient presented cutaneous eruption of nodules on the right bottom and arm. An excisional biopsy revealed cutaneous infiltration composed of two components. The first one consisted of large B-cells with CD20+/MUM1+/BCL2+ phenotype whereas the second one involved the subcutaneous fat in a panniculitic manner, and was CD3+/CD8+/granzyme B+/TCRβF1+. The final diagnosis was CL of primary cutaneous large B-cell lymphoma-leg type (PCLBCL-leg type) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). We report and characterize for the first time coexistent PCLBCL-leg type and SPTCL in a patient.
Published: 2018
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22. 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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23. 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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24. 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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25. Freezing and storage at -20 °C provides adequate preservation of Toxoplasma gondii DNA for retrospective molecular analysis

Author: Hervé Pelloux, Feriel Touafek, Emmanuelle Varlet-Marie, Laurence Delhaes, Frédéric Dalle, Sophie Cassaing, Marie-Pierre Brenier-Pinchart, Hélène Yera, Denis Filisetti, Yvon Sterkers, Patrick Bastien, Université de Bordeaux (UB), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Centre National de référence de la Toxoplasmose (CNRT), Vaccination Antiparasitaire : Laboratoire de Biologie Cellulaire et Moléculaire (LBCM), Université Montpellier 1 (UM1)-Université de Montpellier (UM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire de parasitologie-mycologie, 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), Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), 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]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), 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), 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), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Microbiology (medical), Time Factors, [SDV]Life Sciences [q-bio], education, Biology, Real-Time Polymerase Chain Reaction, Specimen Handling, Toxoplasma gondii DNA, chemistry.chemical_compound, parasitic diseases, Freezing, medicine, Retrospective Studies, toxoplasma gondii, DNA storage, Toxoplasma gondii, amniotic fluid, General Medicine, DNA, Protozoan, medicine.disease, biology.organism_classification, Virology, Toxoplasmosis, Dna storage, Molecular analysis, Infectious Diseases, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Molecular Diagnostic Techniques, congenital toxoplasmosis, Nucleic acid, MESH: DNA, Protozoan/isolation&purification; Freezing, Molecular Diagnostic Technics/methods, Specimen Handling/methods, Toxoplasmosis/diagnosis, real-Time PCR, Toxoplasma, DNA
Abstract: Equipe EA MERS; International audience; Nucleic acid-based testing has become crucial for toxoplasmosis diagnosis. For retrospective (forensic or scientific) studies, optimal methods must be employed for DNA long-term storage. We compared Toxoplasma gondii detection before and after DNA storage using real-time PCR. No significant differences were found depending on duration or storage conditions at -20 °C or -80 °C.
Published: 2014
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25 results on '"Pôle Biologie-Pathologie [CHRU Montpellier]"'

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

2. EGFR-dependent mechanisms of resistance to osimertinib determined by ctDNA NGS analysis identify patients with better outcome

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6. Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

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

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

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

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18. 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

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

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

21. Composite cutaneous lymphoma of diffuse large B-cell lymphoma-leg type and subcutaneous panniculitis-like T-cell lymphoma

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

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

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

25. Freezing and storage at -20 °C provides adequate preservation of Toxoplasma gondii DNA for retrospective molecular analysis

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