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1. Involvement of chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells

Author: Ingrid Langer, F. Guerif, Pascal Froment, Alice Bongrani, Claire Petit, Anthony Estienne, Namya Mellouk, Joëlle Dupont, Christelle Ramé, Ingrid Plotton, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Infertility, Embryology, medicine.medical_specialty, endocrine system diseases, [SDV]Life Sciences [q-bio], CMKLR1, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, In vivo, Internal medicine, medicine, Animals, Humans, Chemerin, Receptor, Progesterone, 030304 developmental biology, 0303 health sciences, Granulosa Cells, 030219 obstetrics & reproductive medicine, biology, business.industry, Obstetrics and Gynecology, Cell Biology, Progesterone secretion, medicine.disease, Follicular fluid, female genital diseases and pregnancy complications, In vitro, Follicular Fluid, Reproductive Medicine, biology.protein, Intercellular Signaling Peptides and Proteins, Female, Receptors, Chemokine, Chemokines, business, Polycystic Ovary Syndrome
Abstract: Polycystic ovarian syndrome (PCOS) is the main cause of infertility in women. It is frequently associated with reduced progesterone production by human luteinised granulosa cells (hlGCs). However, the molecular mechanisms involved in these steroidogenesis alterations in PCOS patients are unclear. In a dihydrotestosterone-induced PCOS mouse model, steroid production is maintained in the setting of chemokine-like receptor 1 (Cmklr1) knockout. Thus, chemerin and chemerin receptors in terms of expression and progesterone regulation could be different in control and PCOS hlGCs. We first confirmed that progesterone levels in both plasma (P < 0.0001) and follicular fluid (FF) (P < 0.0001) were significantly reduced in PCOS normal weight women compared to control women. These data were associated with a lower STAR mRNA expression in both in vivo (P < 0.0001) and in vitro (P < 0.0001) hlGCs from PCOS women. Secondly, chemerin FF levels (P < 0.0001) and RARRES2 (P < 0.05) and CMKLR1 (P < 0.0001) mRNA levels in GCs were higher in PCOS normal weight patients. Thirdly, treatment of hlGCs with a specific nanobody (the VHH CA4910) targeting the human receptor for CMKLR1 leading to its inactivation abolished chemerin-induced progesterone inhibition, suggesting the involvement of CMKLR1 in this process. Furthermore, the inhibition of progesterone secretion induced by chemerin was two-fold higher in PCOS hlGCs (P < 0.05). Moreover, the VHH CA4910 reinstated a normal progesterone secretion with lower concentrations in PCOS hlGCs, suggesting a different chemerin sensitivity between PCOS and control hlGCs. Thus, chemerin, through CMKLR1, could be involved in the steroidogenesis alterations in PCOS hlGCs.
Published: 2021

2. Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer

Author: Jean-François Deleuze, Léa Meunier, Amélie Roehrig, Emmanuel Jacquemin, Victor Renault, Florent Guérin, Stefano Caruso, Sophie Taque, Isabelle Aerts, Catherine Guettier, Monique Fabre, Emmanuel Gonzales, Jill Pilet, Brice Fresneau, Sandra Rebouissou, Laura Molina, C. Chardot, Eric Letouzé, Benedict J.E. Monteiro, Véronique Laithier, Eric Trepo, Quentin Bayard, Jessica Zucman-Rossi, Guillaume Morcrette, Sophie Branchereau, Laurence Brugières, Théo Z. Hirsch, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Fondation Jean Dausset CEPH, Centre National du Génotypage [Evry], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut Curie [Paris], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Paul Brousse, Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Zucman-Rossi, Jessica, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)
Subjects: Hepatoblastoma, Male, Carcinoma, Hepatocellular, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Antineoplastic Agents, Locus (genetics), Biology, Article, Pediatric liver cancer, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Integrated genomic analysis, medicine, Humans, Progenitor cell, Child, Gene, 030304 developmental biology, Progenitor, 0303 health sciences, Chemotherapy, Cancer stem cells, Gene Expression Profiling, Liver Neoplasms, Infant, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Genomics, Sciences bio-médicales et agricoles, medicine.disease, Phenotype, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, Drug Resistance, Neoplasm, Cell culture, Child, Preschool, 030220 oncology & carcinogenesis, Cancer research, Female, Cisplatin, Neoplasm Recurrence, Local, Chemotherapy resistance
Abstract: Pediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between 'Hepatocytic', 'Liver Progenitor' and 'Mesenchymal' molecular subgroups of hepatoblastoma. We showed that during chemotherapy, 'Liver Progenitor' cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies., info:eu-repo/semantics/published
Published: 2021

3. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author: Agnes Nagy, Rene-Olivier Casasnovas, Sameer Bakhshi, Sharon Shacham, Juan-Manuel Sancho, Ronit Gurion, Josée M. Zijlstra, Jatin P. Shah, Miklos Egyed, Brian T. Hill, Krzysztof Warzocha, Gabriel Tremblay, Michael W. Schuster, Fritz Offner, Reda Bouabdallah, Dimitrios Tomaras, Paolo Caimi, Andre Goy, Priyanka Samal, Catherine Thieblemont, Joost S.P. Vermaat, Matthew Ku, Ulrich Jäger, John Kuruvilla, Nagesh Kalakonda, George A Follows, Eric Van Den Neste, Miguel Ángel Canales Albendea, Michael Kauffman, Nada Hamad, Fatima De la Cruz, Patrick Daniele, Marie Maerevoet, Theodoros Vasilakopoulos, Federica Cavallo, Sylvain Choquet, Karyopharm Therapeutics Inc., Newton, MA, U918, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Amsterdam UMC, Addenbrooke's Hospital, Cambridge University NHS Trust, Leiden University Medical Center (LUMC), Institute of Translational Medicine, University of Liverpool, Hackensack University Medical Center [Hackensack], Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cleveland Clinic, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Turin, Hospital Universitario Virgen del Rocío [Sevilla], University Health Network, St Vincent's Hospital Melbourne [Australia], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Medizinische Universität Wien = Medical University of Vienna, University Hospitals Case Medical Center, Tel Aviv University [Tel Aviv], Institute of Hematology and Transfusion Medicine[Warsaw, Poland] (IHTM), Germans Trias i Pujol Hospital, Barcelona Autonomous University, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Ghent University Hospital, National and Kapodistrian University of Athens (NKUA), Semmelweis University [Budapest], Hospital Universitario La Paz, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, and UCL - (SLuc) Service d'hématologie
Subjects: Male, Oncology, Cancer Research, Health utility, FACT-Lym, patient reported outcomes, MESH: Patient Reported Outcome Measures, MESH: Aged, 80 and over, 0302 clinical medicine, Quality of life, Recurrence, Medicine and Health Sciences, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, health, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, MESH: Drug Resistance, Neoplasm, 3. Good health, health-related quality of life, Hydrazines, EQ-5D-5L, patient-reported outcomes, 030220 oncology & carcinogenesis, Female, health utility, Lymphoma, Large B-Cell, Diffuse, MESH: Hydrazines, Adult, disutility of adverse events, medicine.medical_specialty, diffuse large B-cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Refractory, Internal medicine, medicine, Humans, health state utility, selinexor, Patient Reported Outcome Measures, Aged, Health related quality of life, MESH: Humans, business.industry, MESH: Quality of Life, MESH: Adult, Triazoles, medicine.disease, MESH: Male, MESH: Recurrence, Lymphoma, MESH: Triazoles, utility, Drug Resistance, Neoplasm, Relapsed refractory, Quality of Life, MESH: Lymphoma, Large B-Cell, Diffuse, business, MESH: Female, Diffuse large B-cell lymphoma, Progressive disease, 030215 immunology
Abstract: Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.
Published: 2021

4. Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

Author: Akeila Bellahcene, Roberto Ronca, Guillaume Belthier, Patrick Balaguer, Simon Lacroix, Paola Chiodelli, Gaetan Van Simaeys, Andrei Turtoi, Barbara Chiavarina, Julie Pannequin, Olivier Detry, Guy Jerusalem, Serge Goldman, Stéphanie Gofflot, Arnaud Blomme, Eric Fabbrizio, Sara Rezzola, Gilles Doumont, Ambre Giguelay, Bilguun Erkhem-Ochir, Takehiko Yokobori, Vincent Castronovo, Brunella Costanza, Philippe Delvenne, Vincent Cavaillès, Emmanuel Di Valentin, 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), GIGA [Université Liège], Université de Liège, University of Brescia, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Center for Microscopy and Molecular Imaging (IBMM - CMMI), Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Gunma University, Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and UM, Faculté de Médecine
Subjects: 0301 basic medicine, Colorectal Neoplasms -- blood supply -- metabolism -- pathology, Colorectal cancer, Angiogenesis, Endothelial cells, Cell, Medicine (miscellaneous), Apoptosis, alternative TGFβ signaling, Liver Neoplasms -- blood supply -- metabolism -- secondary, Liver metastases, Mice, 0302 clinical medicine, Circulating tumor cell, Cell Movement, Transforming Growth Factor beta, Tumor Cells, Cultured, Medicine, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Extracellular Matrix Proteins, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neovascularization, Pathologic, Liver Neoplasms, Sciences bio-médicales et agricoles, Prognosis, endothelial cells, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Neovascularization, Pathologic -- metabolism -- pathology, 030220 oncology & carcinogenesis, Signal transduction, Colorectal Neoplasms, Signal Transduction, Research Paper, Extracellular Matrix Proteins -- genetics -- metabolism, Alternative TGFβ signaling, Stromal cell, 03 medical and health sciences, Settore MED/04 - PATOLOGIA GENERALE, Biomarkers, Tumor, Animals, Humans, Cell Proliferation, business.industry, Transforming Growth Factor beta -- genetics -- metabolism, medicine.disease, Xenograft Model Antitumor Assays, eye diseases, 030104 developmental biology, Cancer cell, Cancer research, Sciences pharmaceutiques, business, liver metastases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, Tumor -- genetics -- metabolism, TGFBI
Abstract: Colorectal cancer (CRC) cells are traditionally considered unresponsive to TGFβ due to mutations in the receptors and/or downstream signaling molecules. TGFβ influences CRC cells only indirectly via stromal cells, such as cancer-associated fibroblasts. However, CRC cell ability to directly respond to TGFβ currently remains unexplored. This represents a missed opportunity for diagnostic and therapeutic interventions. Methods: We examined whether cancer cells from primary CRC and liver metastases respond to TGFβ by inducing TGFβ-induced protein ig-h3 (TGFBI) expression, and the contribution of canonical and non-canonical TGFβ signaling pathways to this effect. We then investigated in vitro and in vivo TGFBI impact on metastasis formation and angiogenesis. Using patient serum samples and an orthotopic mouse model of CRC liver metastases we assessed the diagnostic/tumor targeting value of novel antibodies against TGFBI. Results: Metastatic CRC cells, such as circulating tumor cells, directly respond to TGFβ. These cells were characterized by the absence of TGFβ receptor mutations and the frequent presence of p53 mutations. The pro-tumorigenic program orchestrated by TGFβ in CRC cells was mediated through TGFBI, the expression of which was positively regulated by non-canonical TGFβ signaling cascades. TGFBI inhibition was sufficient to significantly reduce liver metastasis formation in vivo. Moreover, TGFBI pro-tumorigenic function was linked to its ability to stimulate angiogenesis. TGFBI levels were higher in serum samples from untreated patients with CRC than in patients who were receiving chemotherapy. A radiolabeled anti-TGFBI antibody selectively targeted metastatic lesions in vivo, underscoring its diagnostic and therapeutic potential. Conclusions: TGFβ signaling in CRC cells directly contributes to their metastatic potential and stromal cell-independence. Proteins downstream of activated TGFβ, such as TGFBI, represent novel diagnostic and therapeutic targets for more specific anti-metastatic therapies., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

5. Characteristics and outcomes of acute respiratory distress syndrome related to COVID-19 in Belgian and French intensive care units according to antiviral strategies: the COVADIS multicentre observational study

Author: David Grimaldi, Nadia Aissaoui, Gauthier Blonz, Giuseppe Carbutti, Romain Courcelle, Stephane Gaudry, Aurelie Gaultier, Alain D’hondt, Julien Higny, Geoffrey Horlait, Sami Hraiech, Laurent Lefebvre, Francois Lejeune, Andre Ly, Michael Piagnerelli, Bertrand Sauneuf, Nicolas Serck, Thibaud Soumagne, Piotr Szychowiak, Julien Textoris, Benoit Vandenbunder, Christophe Vinsonneau, Jean- Baptiste Lascarrou, for the COVADIS study group, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Services des soins intensifs, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Départemental site de la Roche-sur-Yon (CHD de la Roche-sur-Yon), hospital universitaire de Mons-Hainaut, Hopital de Jolimont, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de Méthodologie et Biostatistique, Direction de la Recherche [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Ambroise Paré [Mons, Belgium], CHU Dinant-Godinne UCL Namur [Yvoir, Belgique], Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier du Pays d'Aix, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université libre de Bruxelles (ULB), Grand Hôpital de Charleroi [Belgium], Service de Réanimation Polyvalente [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), Saint Pierre clinic of Ottignies (CSPO), Saint Pierre clinic of Ottignies, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Médecine Intensive et Réanimation [Tours], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau CRICS-TRIGGERSEP [CHRU Tours] (F-CRIN research network), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hospices Civils de Lyon (HCL), Laboratoire Commun de Recherche Hospices Civils de Lyon – bioMérieux (Cancer Biomarkers Research Group), Hospices Civils de Lyon (HCL)-BIOMERIEUX, Hôpital Privé d'Antony, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, and COVADIS study group: Patrick Biston, Gwenhael Colin, Oriane de Maere, Nathan Ebstein, Stephan Ehrmann, Frederic Foret, Lionel Haentjens, Thibault Helbert, Jean-Baptiste Mesland, Celine Monard, Nicolas Mongardon, Gregoire Ottavy, Thomas Pasau, Gael Piton, Ester Ponzetto, Caroline Sejourne, Morgane Snacken, Xavier Souloy, Aude Sylvestre, Nicolas Tartrat, Cedric Vanbrussel
Subjects: ARDS, medicine.medical_specialty, medicine.medical_treatment, Remdesivir, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lopinavir, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Internal medicine, medicine, 030212 general & internal medicine, Renal replacement therapy, Mechanical ventilation, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Ritonavir, business.industry, Research, Acute kidney injury, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, Cohort, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, medicine.drug, Hydroxychloroquine
Abstract: Background Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). Methods Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”. Results We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59). Conclusion In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT
Published: 2020

6. Neurological improvement predicts clinical outcome after acute basilar artery stroke thrombectomy

Author: Mathilde Aubertin, Cyril Dargazanli, Maud Guillen, François Eugène, Adrien Guenego, Raphaël Blanc, Ronda Lun, Amel Benali, Etis Investigators, G Walker, David Weisenburger-Lile, B Lapergue, Romain Bourcier, Julien Labreuche, Robert Fahed, Arturo Consoli, Lili Detraz, Célina Ducroux, Stephane Vannier, Ludovic Lucas, Sébastien Richard, Michel Piotin, Benjamin Gory, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Hôpital Foch [Suresnes], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, CHU Bordeaux [Bordeaux], Hôpital Gui de Chauliac [Montpellier], The Ottawa Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Gui de Chauliac [CHU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Revascularization, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, medicine.artery, Vertebrobasilar Insufficiency, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Basilar artery, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Stroke, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Thrombectomy, business.industry, Endovascular Procedures, Odds ratio, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Neurology, Basilar Artery, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE Mechanical thrombectomy (MT) is the standard of care for patients with anterior circulation large vessel occlusion. Early neurological improvement (ENI), defined as a reduction of ≥ 8 on the National Institutes of Health Stroke Scale (NIHSS) compared with baseline score, or an NIHSS score of 0 or 1 at 24 h after MT, is a strong predictor of 3-month favorable outcome in such patients. The impact of ENI after MT in stroke patients with basilar artery occlusion (BAO) on 3-month outcome is not clear. We aimed to study the effects of ENI in patients with BAO. METHODS We performed a retrospective analysis of a multicenter prospective cohort of all consecutive stroke patients with BAO who underwent MT. We compared clinical outcomes between BAO patient groups according to ENI status. Multivariate analyses were performed to determine the impact of ENI on favorable 90-day outcome (modified Rankin scale score 0-3) and to report factors contributing to ENI. RESULTS A total of 237 patients were included. ENI was observed in 70 patients (30%). Outcomes were significantly better in ENI-positive patients, with 84% achieving favorable outcome (mRS score 0-3) at 3 months versus 30% for ENI-negative patients (P
Published: 2020

7. Natural T Cell Epitope Containing Methyl Lysines on Mycobacterial Heparin-Binding Hemagglutinin

Author: Jérôme Segers, Emmanuelle Petit, Oleg Melnyk, Véronique Corbière, Sophie Lecher, Rémi Desmet, Françoise Mascart, Marc Loyens, Camille Locht, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Chemical Biology of Flatworms [Lille] (CBF), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de La Rochelle (ULR), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and La Rochelle Université (ULR)
Subjects: medicine.drug_class, T-Lymphocytes, [SDV]Life Sciences [q-bio], T cell, Mycobacterium smegmatis, Immunology, Epitopes, T-Lymphocyte, Hemagglutinin (influenza), Peptide, Monoclonal antibody, Methylation, Epitope, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Antigen, Lectins, Immunologie, medicine, Humans, [CHIM]Chemical Sciences, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Antigens, Bacterial, biology, Chemistry, Lysine, Mycobacterium tuberculosis, biology.organism_classification, Molecular biology, Sciences biomédicales, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Protein Processing, Post-Translational, 030215 immunology
Abstract: T cell epitopes are mostly nonmodified peptides, although posttranslationally modified peptide epitopes have been described, but they originated from viral or self-proteins. In this study, we provide evidence of a bacterial methylated T cell peptide epitope. The mycobacterial heparin-binding hemagglutinin (HBHA) is a protein Ag with a complex C-terminal methylation pattern and is recognized by T cells from humans latently infected with Mycobacterium tuberculosis. By comparing native HBHAwith recombinant HBHA produced in Mycobacterium smegmatis (rHBHA-Ms), we could link antigenic differences to differences in the methylation profile. Peptide scan analyses led to the discovery of a peptide containing methyl lysines recognized by a mAb that binds to native HBHA ∼100-fold better than to rHBHA-Ms. This peptide was also recognized by T cells from latently infected humans, as evidenced by IFN-g release upon peptide stimulation. The nonmethylated peptide did not induce IFN-g, arguing that the methyl lysines are part of the T cell epitope., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

8. The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Author: Roberts, Jason, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, de Waele, Jan, Deans, Renae, Eastwood, Glenn, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios, Lassig-Smith, Melissa, Laterre, Pierre-Francois, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne, Rello, Jordi, Roberts, Darren, Roberts, Michael, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi, Paul, Sanjoy, Lipman, Jeffrey, Andresen, Max, Baltazar, Sónia, Barbar, Saber, Costa, Eulália, Durand, Dominique, Freitas, Ricardo, Frey, Otto, Guerra Valero, Yarmarly, Haughton, Margaret, Koeberer, Andreas, Kollef, Marin, Klein, Kerenaftali, Mehta, Ravindra, Mckenzie, Cathy, Muller, Laurent, Nair, Priya, Nayyar, Vineet, Ordóñez Mejia, Jenny, Panagou, Georgia-Laura, Paxton, Jody, Peck, Leah, Samanta, Mayukh, Vincent, Jean-Louise, Wan, Ruth, Young, Helen, University of Southern Queensland (USQ), Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Princess Alexandra Hospital, Brisbane, SMARRT Study, ANZICS Clinical Trials Group, The Chinese University of Hong Kong [Hong Kong], Austin Hospital [Melbourne], Austin Health, The Ottawa Hospital, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Westmead Hospital [Sydney], The University of Sydney, The Queen Elizabeth Hospital (TQEH), University of Adelaide, Monash University [Melbourne], Royal Darwin Hospital, Flinders University [Adelaide, Australia], National Critical Care and Trauma Response Centre (Darwin) (NCCTRC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Corporació Sanitària Parc Taulí, Barcelona Biomedical Research Park (PRBB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, QIMR Berghofer Medical Research Institute, Centro Hospitalar e Universitário [Coimbra], Athens Naval Hospital, University of Queensland [Brisbane], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Kliniken Landkreis Heidenheim, Melbourne EpiCentre, The Royal Melbourne Hospital, Hospital Clínic de Barcelona (ICMiD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Nepean Hospital, Ghent University Hospital, Universidad de Santiago de Chile [Santiago] (USACH), University of Sydney and Nepean Hospital, Hospital Tengku Ampuan Afzan (HTAA), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital of Ioannina, Royal Brisbane & Women's Hospital, Cliniques universitaires St Luc [Bruxelles], Guy's and St Thomas' Hospital [London], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universitat Internacional de Catalunya [Barcelona] (UIC), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, International Islamic University Malaysia [Kuala Lumpur], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of South Australia [Adelaide], Basil Hetzel Institute (BHI), Translational Research Institute (TRI), Gold Coast University Hospital, University Hospital of Tarragona 'Joan XXIII', University Rovirai Virgili de Tarragona (URV), Ochsner Medical Center, The Queen Elizabeth Hospital, Hospital Clínic de Barcelona, Roberts, Jason A., Joynt, Gavin M., Lee, Anna, Choi, Gordon, Roberts, Michael S., Sinnollareddy, Mahipal, and Lipman, Jeffrey
Subjects: 0301 basic medicine, Continuous renal replacement therapy, medicine.medical_treatment, continuous renal replacement therapy, Antibiotics, urologic and male genital diseases, MESH: Meropenem, 030226 pharmacology & pharmacy, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Prospective Studies, pharmacokinetic, extended daily dialysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Extended daily dialysis, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Renal Replacement Therapy, Infectious Diseases, MESH: Critical Illness, Vancomycin, beta-lactam, medicine.drug, MESH: Piperacillin, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Critical Illness, Beta-lactam, 030106 microbiology, Pharmacokinetic, Meropenem, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Internal medicine, Intensive care, medicine, Humans, Trough Concentration, Dosing, Renal replacement therapy, Piperacillin, MESH: Humans, business.industry, MESH: Prospective Studies, renal clearance, MESH: Renal Replacement Therapy, business, Renal clearance
Abstract: Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
Published: 2020

9. Integration of the M6 Cyberknife in the Moderato Monte Carlo platform and prediction of beam parameters using machine learning

Author: A. Wagner, D. Van Gestel, E. Rault, F. Crop, K.N.D. Brou Boni, Nick Reynaert, Thomas Lacornerie, Centre de Recherches et d'Informations Scientifiques et Techniques Appliquées aux Lithiases (CRISTAL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Speedup, Computer science, [SDV]Life Sciences [q-bio], Physics::Medical Physics, Monte Carlo method, Biophysics, General Physics and Astronomy, Machine learning, computer.software_genre, Models, Biological, Linear particle accelerator, 030218 nuclear medicine & medical imaging, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Cyberknife, Humans, Radiotherapy dose, Computer Simulation, Radiology, Nuclear Medicine and imaging, business.industry, Radiotherapy Planning, Computer-Assisted, X-Rays, Radiotherapy Dosage, Equipment Design, General Medicine, 030220 oncology & carcinogenesis, Cathode ray, Radiotherapy, Intensity-Modulated, Artificial intelligence, Particle Accelerators, Tomography, X-Ray Computed, business, Monte Carlo Method, computer, Beam (structure), Energy (signal processing)
Abstract: Purpose This work describes the integration of the M6 Cyberknife in the Moderato Monte Carlo platform, and introduces a machine learning method to accelerate the modelling of a linac. Methods The MLC-equipped M6 Cyberknife was modelled and integrated in Moderato, our in-house platform offering independent verification of radiotherapy dose distributions. The model was validated by comparing TPS dose distributions with Moderato and by film measurements. Using this model, a machine learning algorithm was trained to find electron beam parameters for other M6 devices, by simulating dose curves with varying spot size and energy. The algorithm was optimized using cross-validation and tested with measurements from other institutions equipped with a M6 Cyberknife. Results Optimal agreement in the Monte Carlo model was reached for a monoenergetic electron beam of 6.75 MeV with Gaussian spatial distribution of 2.4 mm FWHM. Clinical plan dose distributions from Moderato agreed within 2% with the TPS, and film measurements confirmed the accuracy of the model. Cross-validation of the prediction algorithm produced mean absolute errors of 0.1 MeV and 0.3 mm for beam energy and spot size respectively. Prediction-based simulated dose curves for other centres agreed within 3% with measurements, except for one device where differences up to 6% were detected. Conclusions The M6 Cyberknife was integrated in Moderato and validated through dose re-calculations and film measurements. The prediction algorithm was successfully applied to obtain electron beam parameters for other M6 devices. This method would prove useful to speed up modelling of new machines in Monte Carlo systems.
Published: 2020

10. When one-two-three beats two-one-three: Tracking the acquisition of the verbal number sequence

Author: Amandine Van Rinsveld, Steve Majerus, Michel Fayol, Christine Schiltz, Center for Research in Cognition & Neurosciences [Brussels] (ULB/CRCN), Faculté des Sciences psychologiques et de l'éducation [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institute of Cognitive Science and Assessment, Education, Culture, Cognition and Society Research Unit - University of Luxembourg, Psychology and Neuroscience of Cognition Research Unit - Université de Liège, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Memory, Long-Term, Counting, Experimental and Cognitive Psychology, Development, Verbal learning, computer.software_genre, Language Development, Psychologie du développement cognitif, 050105 experimental psychology, 03 medical and health sciences, Child Development, Number words, 0302 clinical medicine, Arts and Humanities (miscellaneous), Developmental and Educational Psychology, Cognitive development, Code (cryptography), Humans, 0501 psychology and cognitive sciences, Child, Imagerie cérébrale fonctionnelle, Language, Sequence (medicine), Recall, Verbal number sequence, business.industry, 05 social sciences, Neurosciences cognitives, Verbal Learning, Child development, Language development, Memory, Short-Term, Child, Preschool, Psycholinguistique, Mental Recall, [SCCO.PSYC]Cognitive science/Psychology, Female, Tracking (education), Artificial intelligence, business, Psychology, Psychologie cognitive, Sciences cognitives, computer, 030217 neurology & neurosurgery, Natural language processing
Abstract: Learning how to count is a crucial step in cognitive development, which progressively allows for more elaborate numerical processing. The existing body of research consistently reports how children associate the verbal code with exact quantity. However, the early acquisition of this code, when the verbal numbers are encoded in long-term memory as a sequence of words, has rarely been examined. Using an incidental assessment method based on serial recall of number words presented in ordered versus non-ordered sequences (e.g. one-two-three vs. two-one-three), we tracked the progressive acquisition of the verbal number sequence in children aged 3–6 years. Results revealed evidence for verbal number sequence knowledge in the youngest children even before counting is fully mastered. Verbal numerical knowledge thus starts to be organized as a sequence in long-term memory already at the age of 3 years, and this numerical sequence knowledge is assessed in a sensitive manner by incidental rather than explicit measures of number knowledge., info:eu-repo/semantics/published
Published: 2020

11. Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients

Author: Amelia Głowaczewska, Lukasz Matusiak, Mateja Dolenc-Voljč, Nayera H. Moftah, Jorge Romaní, V. Sigsgaard, Burcu Beksaç, Jan Lapins, Hessel H. van der Zee, Moetaz El-Domyati, Errol P. Prens, Eugènia Agut-Busquet, Axel Patrice Villani, Lerinza van den Worm, Mehmet Ali Gürer, Lennart Emtestam, Hassan Riad Kottb, Annika M J D Vanlaerhoven, Farida Benhadou, Maïa Delage-Toriel, Lisa Weibel, Hossam Abdel-Wahab, José C. Pascual, Ditte Marie Saunte, Vincenzo Bettoli, Véronique Del Marmol, Thi Lam, Dorra Bouazzi, Giada Calamo, Mohammad Fatani, Pierre-Andre Becherel, Martin Theiler, Peter Theut Riis, Jacek C Szepietowski, Aude Nassif, Philippe Guillem, Rania Abdelghani, Carol Hlela, Nejib Doss, Gregor B.E. Jemec, Naomi N Kappe, Zealand University Hospital [Roskilde, Denmark], University of Copenhagen = Københavns Universitet (UCPH), Service de dermatologie [HCL Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Clinique du Val d'Ouest, Hospital Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-FISABIO), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Minia University, Al-Azhar University [Cairo, Egypt], Armed Forces College of Medicine [Cairo, Egypt] (AFCM), Universitat Autònoma de Barcelona (UAB), Hospital de la Santa Creu i Sant Pau, Hospital Universitari Parc Taulí of Sabadell, Barcelona, University of Cape Town, Red Cross Children's Hospital [Cape Town, South Africa], Azienda Ospedaliero Universitaria di Ferrara [Cona, Italy], Gazi University, Wrocław Medical University, Karolinska Institutet [Stockholm], Hamad medical corporation, Hera General Hospital [Makkah, Saudi Arabia], University Children’s Hospital Zurich, University hospital of Zurich [Zurich], Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Hôpital privé d’Antony, University of Ljubljana, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Department of Dermatology, Military Hospital of Tunis, Hôpital militaire de Tunis, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), University of Copenhagen = Københavns Universitet (KU), Wroclaw Medical University [Wrocław, Pologne], Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], and Dermatology
Subjects: Male, Hirsutism, [SDV]Life Sciences [q-bio], Dermatologic Surgical Procedures, Administration, Oral, Disease, Comorbidity, Severity of Illness Index, Body Mass Index, 030207 dermatology & venereal diseases, 0302 clinical medicine, Risk Factors, Acne Vulgaris, Medicine, Hidradenitis suppurativa, Child, Children, Acne, hirsutism, Pediatric, medicine.diagnostic_test, Clindamycin, Smoking, General Medicine, Sciences bio-médicales et agricoles, 3. Good health, Anti-Bacterial Agents, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, Rifampin, medicine.drug, medicine.medical_specialty, Adolescent, Physical examination, Dermatology, Administration, Cutaneous, 03 medical and health sciences, Young Adult, Pilonidal Sinus, Internal medicine, Humans, Obesity, business.industry, Resorcinols, Acne inversa, Tetracycline, medicine.disease, Cross-Sectional Studies, business, Rifampicin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases., info:eu-repo/semantics/published
Published: 2020

12. Modalités de mobilisation des cellules souches hématopoïétiques autologues et objectifs cellulaires en cellules CD34 + : recommandations de la Société francophone de greffe de mœlle et de thérapie cellulaire (SFGM-TC)

Author: Fati Hamzy, Laure Vincent, Anne Brignier, Christine Giraud, Thi Ngoc Phuong Huynh, Francisca Nacimento, Aurélie Levavasseur, Virginie Ader, John De Vos, Katia Bellegarde, Marie-Agnès Guerout-Verite, Yves Rousseau, Ibrahim Yakoub-Agha, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Etablissement français du sang [Rennes] (EFS Bretagne), Université Internationale Abulcasis des Sciences de la Santé (UIASS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Unité de Recherches sur la Génétique des Protéines Humaines [Bois-Guillaume] (U78 INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CCSD, Accord Elsevier
Subjects: Cancer Research, medicine.medical_specialty, MESH: Heterocyclic Compounds, Bone marrow transplantation, medicine.medical_treatment, Autogreffe de cellules souches, Mobilization, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Autologous stem cell transplantation, 030204 cardiovascular system & hematology, MESH: Cell Separation, Cellules souches hématopoïétiques, MESH: Hematopoietic Stem Cell Mobilization, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Risk Factors, Cell dose, medicine, Autologous transplantation, Radiology, Nuclear Medicine and imaging, MESH: Hematopoietic Cell Growth Factors, MESH: Hematopoietic Stem Cell Transplantation, Mobilisation, Gynecology, MESH: Humans, MESH: Cell Count, business.industry, Plerixafor, MESH: Antigens, CD34, Hematology, General Medicine, MESH: Transplantation, Autologous, MESH: Blood Component Removal, Oncology, MESH: Practice Patterns, Physicians', MESH: Antineoplastic Agents, MESH: Bone Marrow, MESH: Granulocyte Colony-Stimulating Factor, Stem cell, business, Hematopoietic stem cells, 030215 immunology, medicine.drug
Abstract: The modalities of mobilization of hematopoietic stem cells in autologous transplantation have evolved in recent years. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 9th hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2018 in Lille, France, to conduct a review of current practices of the society centers and of international recommendations. The cell dose objectives have been revised. The modalities of mobilization including the use of plerixafor have been specified allowing reaching the objectives of collection while limiting the number of apheresis. Collections failures have become exceptional., Les modalités de mobilisation des cellules souches hématopoïétiques dans le cadre de la greffe autologue ont évolué ces dernières années. Dans le cadre des neuvièmes Ateliers d’harmonisation des pratiques en greffe de cellules souches hématopoïétiques de la Société Francophone de Greffe de Mœlle et de Thérapie Cellulaire (SFGM-TC) qui ont eu lieu à Lille en septembre 2018, un groupe de travail s’est réuni dans le but de réaliser un état des lieux des pratiques des centres de la société et des recommandations internationales. Les objectifs de richesse des greffons ont été revus à la hausse. Les modalités de mobilisation, y compris d’utilisation du plerixafor, ont été précisées, dans l’objectif d’atteindre les objectifs de recueil tout en limitant le nombre de cytaphérèses. Les échecs de recueils sont devenus exceptionnels.
Published: 2020

13. Compatibility of FIASMA Pharmacokinetics With Study End Points?

Author: Gwenolé Loas, Pascal Le Corre, CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio], 030226 pharmacology & pharmacy, Article, SARS‐CoV‐2, intubation, 03 medical and health sciences, medications, 0302 clinical medicine, Pharmacokinetics, COVID‐19, Medicine, Pharmacology (medical), ceramide, acid sphingomyelinase, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, treatment, business.industry, Articles, mortality, Reliability engineering, [SDV] Life Sciences [q-bio], Compatibility (mechanics), FIASMA, business
Abstract: Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS‐CoV‐2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID‐19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID‐19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time‐to‐event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow‐up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58‐0.87; p
Published: 2022

14. Comment on ’Comparison of losartan and amlodipine effects on the outcomes of patient with COVID-19 and primary hypertension: A randomised clinical trial’

Author: Mojtaba Varshochi, Akbar Sharifi, Mehdi Maleki, Azam Esmailnajad, Armin Sadeghi, Ali Taghizadieh, Khalil Ansarin, Parviz Saleh, Ramin Zand, Masoud Ahangari Maleki, Zahra Soroureddin, Niusha Kalami, Haleh Rezaee, Mehdi Haghdoost, Masoud Nouri-Vaskeh, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université de Rennes 1 - Faculté des sciences pharmaceutiques et biologiques (UR1 Pharmacie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes - Faculté des sciences pharmaceutiques et biologiques (UR Pharmacie), and Université de Rennes (UR)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Blood Pressure, 030204 cardiovascular system & hematology, Losartan, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Amlodipine, Antihypertensive Agents, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Original Paper, SARS-CoV-2, business.industry, Mortality rate, COVID-19, General Medicine, Middle Aged, Original Papers, 3. Good health, Icu admission, Clinical trial, Infectious Diseases, Treatment Outcome, Blood pressure, Hypertension, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID‐19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID‐19. Methods In this randomised clinical trial, hospitalised patients with COVID‐19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30‐day mortality rate and length of hospital stay. Results The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30‐day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). Conclusions There was no priority in losartan or amlodipine administration in COVID‐19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first‐line anti‐HTN medications in COVID‐19.
Published: 2021

15. Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy

Author: Guillaume Taieb, Christian Larroque, Luca Lanfranco, I. Szwarc, Emilien Delmont, Vincent Pernin, Anaïs Beyze, Nicole Bec, Boucraut José, Maxime Teisseyre, Marie Christine Machet, Jérôme Devaux, Moglie Le Quintrec, Clair Geneste, Anthony Chauvin, Claire Rigothier, Hélène Perrochia, Catalano Concetta, Nicolas Mavroudakis, 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), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Gui de Chauliac [CHU Montpellier], Université de Tours (UT), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service ORL [Hôpital Gui de Chauliac] (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Gui de Chauliac [Montpellier], Université de Tours, Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Contactin 1, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Chronic inflammatory demyelinating polyneuropathy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Glomerulonephritis, Membranous, Immunoglobulin G, 03 medical and health sciences, chronic inflammatory demyelinating polyneuropathy, 0302 clinical medicine, Membranous nephropathy, Antigen, medicine, Humans, Autoantibodies, 030304 developmental biology, Autoimmune disease, 0303 health sciences, biology, business.industry, nephrotic syndrome, Receptors, Phospholipase A2, Glomerular basement membrane, Autoantibody, membranous nephropathy, medicine.disease, immunoglobulin G type 4, 3. Good health, contactin-1, medicine.anatomical_structure, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Nephrology, biology.protein, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Primary membranous nephropathy (MN) is an autoimmune glomerular disease in which autoantibodies are directed against podocyte proteins. In about 80% of cases the main targeted antigen is the phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1 antibodies are mainly immunoglobulin G type 4 (IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target antigen, we analyzed kidney biopsies from five patients positive for anti-contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating polyneuropathy. Eluted IgG from biopsy sections against contactin 1 and nerve tissue were screened. Western blot revealed contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of contactin 1 and IgG4 on the glomerular basement membrane of these patients. Glomerular contactin 1 was absent in patients with anti-PLA2R1-associated MN or membranous lupus nephritis or a healthy control. The eluted IgG from contactin 1-positive biopsy sections but not the IgG eluted from patients with PLA2R1 MN bound conactin 1 with the main eluted subclass IgG4. Eluted IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-conactin 1 antibody. Thus, contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating polyneuropathy. However, the precise pathophysiology remains to be elucidated.
Published: 2021

16. Chromosome-level genome assembly reveals homologous chromosomes and recombination in asexual rotifer Adineta vaga

Author: Karine Van Doninck, Richard Cordaux, Thomas Lenormand, Clément Gilbert, Karine Labadie, Lyam Baudry, Julie Virgo, Boris Hespeels, Djampa K. L. Kozlowski, Jitendra Narayan, Alessandro Derzelle, Marie Cariou, Antoine Limasset, Florence Gaudray, Bernard Hallet, Martial Marbouty, Etienne Danchin, Antoine Houtain, Rohan Arora, Matthieu Terwagne, Corinne Cruaud, Nadège Guiglielmoni, Jean-François Flot, Romain Koszul, Paul Simion, Emilien Nicolas, Marc Llirós, Université de Namur [Namur] (UNamur), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Université libre de Bruxelles (ULB), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Evolution, génomes, comportement et écologie (EGCE), Institut de Recherche pour le Développement (IRD)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Louvain Institute of Biomolecular Science and Technology (LIBST), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Interuniversity Institute of Bioinformatics in Brussels (IB2), Université libre de Bruxelles (ULB)-Vrije Universiteit Brussel (VUB), This project received funding from the Horizon 2020 research and innovation program under European Research Council (ERC) grant agreement 725998 (RHEA) and from BELSPO PRODEX for the ESA selected ILSRA-2014-0106 Project to K.V.D., from the Fédération Wallonie-Bruxelles via an 'Action de Recherche Concertée' (ARC) grant to K.V.D. and B.Ha., from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 764840 to J.-F.F. (ITN IGNITE), from the Fédération Wallonie-Bruxelles via an Action de Recherche Concertée (ARC) grant to J.-F.F., from the European Research Council under the Horizon 2020 Program (ERC grant agreement 260822) and JPI-EC-AMR STARCS ANR-16-JPEC-0003-05 grant to R.K., and through funding by the French Government 'Investissement d’Avenir' program FRANCE GENOMIQUE (ANR-10-INBS-09). E.N. obtained an FSR UNamur fund. A.H., A.D., and R.A. are Research Fellows of the Fonds de la Recherche Scientifique—FNRS., ANR-16-JPEC-0003,STARCS,Selection and Transmission of Antimicrobial Resistance in Complex Systems(2016), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 764840,IGNITE, European Project: 260822,EC:FP7:ERC,ERC-2010-StG_20091118,DICIG(2011), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Sequence assembly, Rotifer, Evolution des espèces, Biology, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Homologous chromosome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Océanographie biologique, Clade, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Biologie moléculaire, Chromosome, Adineta vaga, Genome, LOH, Adineta vaga, bdelloid rotifer, biology.organism_classification, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, chemistry, Génétique, cytogénétique, Systématique des espèces [zoologie], DNA, Recombination
Abstract: Bdelloid rotifers are notorious as a speciose ancient clade comprising only asexual lineages. Thanks to their ability to repair highly fragmented DNA, most bdelloid species also withstand complete desiccation and ionizing radiation. Producing a well-assembled reference genome is a critical step to developing an understanding of the effects of long-term asexuality and DNA breakage on genome evolution. To this end, we present the first high-quality chromosome-level genome assemblies for the bdelloid Adineta vaga, composed of six pairs of homologous (diploid) chromosomes with a footprint of paleotetraploidy. The observed large-scale losses of heterozygosity are signatures of recombination between homologous chromosomes, either during mitotic DNA double-strand break repair or when resolving programmed DNA breaks during a modified meiosis. Dynamic subtelomeric regions harbor more structural diversity (e.g. chromosome rearrangements, transposable elements, and haplotypic divergence). Our results trigger the reappraisal of potential meiotic processes in bdelloid rotifers and help unravel the factors underlying their long-term asexual evolutionary success., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

17. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma

Author: Didier Blaise, Tycel Phillips, Jason T. Romancik, Roch Houot, Robert Lowsky, Martina Sollini, Jean Marc Schiano De Colella, Amer Beitinjaneh, Gunjan L. Shah, Lazaros J. Lekakis, Stephen D. Smith, Paolo Corradini, Mohamad Mohty, Maryam Rahimian, Luca Castagna, Taiga Nishihori, Asad Bashey, Talha Badar, Reid W. Merryman, Mehdi Hamadani, Carmelo Carlo-Stella, Dipenkumar Modi, Sally Arai, Kamal Bouabdallah, Valter Torri, Joseph P. McGuirk, Guillaume Manson, Anna Guidetti, Yi-Bin Chen, Hatcher J. Ballard, Julio C. Chavez, Pier Luigi Zinzani, Tatyana Feldman, Sunita Nathan, Anurag K. Singh, Massimo Magagnoli, Marie Pierre Moles-Moreau, Beatrice Casadei, Anthony Serritella, Michael Byrne, Radhakrishnan Ramchandren, Miguel-Angel Perales, Chiara De Philippis, Samantha Jaglowski, Justin Kline, Remy Dulery, Laura Giordano, Alex F. Herrera, Jonathon B. Cohen, Philippe Armand, Armando Santoro, Aspasia Stamatoulas, Stephen M. Ansell, Michael A. Spinner, Lori Dahncke, Corentin Orvain, Chloé Spilleboudt, Geoffrey Shouse, Robin Joyce, Vincent T. Ho, Matthew J. Frigault, Ryan C. Lynch, Uttam Rao, Jakub Svoboda, David A. Bond, Yago Nieto, Dana-Farber Cancer Institute [Boston], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, Ohio State University [Columbus] (OSU), Stanford University, Memorial Sloane Kettering Cancer Center [New York], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Humanitas University [Milan] (Hunimed), P01 CA23766, U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | National Institutes of Health, 20575, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Merryman R.W., Castagna L., Giordano L., Ho V.T., Corradini P., Guidetti A., Casadei B., Bond D.A., Jaglowski S., Spinner M.A., Arai S., Lowsky R., Shah G.L., Perales M.-A., De Colella J.M.S., Blaise D., Herrera A.F., Shouse G., Spilleboudt C., Ansell S.M., Nieto Y., Badar T., Hamadani M., Feldman T.A., Dahncke L., Singh A.K., McGuirk J.P., Nishihori T., Chavez J., Serritella A.V., Kline J., Mohty M., Dulery R., Stamatoulas A., Houot R., Manson G., Moles-Moreau M.-P., Orvain C., Bouabdallah K., Modi D., Ramchandren R., Lekakis L., Beitinjaneh A., Frigault M.J., Chen Y.-B., Lynch R.C., Smith S.D., Rao U., Byrne M., Romancik J.T., Cohen J.B., Nathan S., Phillips T., Joyce R.M., Rahimian M., Bashey A., Ballard H.J., Svoboda J., Torri V., Sollini M., De Philippis C., Magagnoli M., Santoro A., Armand P., Zinzani P.L., and Carlo-Stella C.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, allogenic stem cell transplantation, PD-1 blockade, Hodgkin lymhpoma, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Salvage therapy, 0302 clinical medicine, Young adult, Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Allogeneic transplantation, Cyclophosphamide, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, Survival rate, Aged, Retrospective Studies, Salvage Therapy, business.industry, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Blockade, Transplantation, 030104 developmental biology, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.
Published: 2021

18. The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper

Author: Sergio Pillon, Mariella Catalano, Benjamin Brenner, Zsolt Pecsvarady, Ismail Elalamy, Joseph Lewis, Jean-Claude Wautrecht, D. Olinic, Vincent Maréchal, Mouna Sassi, Isabelle Mahé, Anna Falanga, Nusrat Jabeen, Charles A. Carter, Mary-Paula Colgan, Alexander Makatsariya, Alfonso Tafur, Kasse Aa, Tazi Mezalek Zoubida, Meletios-Athanasios Dimopoulos, Michèle Sabbah, Darko Antic, Yiannis Theodorou, Alex C. Spyropoulos, Vladimir Chekhonin, Meganathan Kannan, Katalin Farkas, Peter Klein-Wegel, Job Harenberg, P Massamba Mbaye, Joseph Gligorov, Manuel Monreal Bosch, Grigoris T. Gerotziafas, Pier Luigi Antignani, Hikmat Abdel-Razeq, James D. Douketis, Gerit Schernthaner, Petros Agathaggelou, Ali T. Taher, Jawed Fareed, Essam Abo Elnazar, Irina Panovska-Stavridis, Patrick Van Dreden, Fabio Leivano, Gerry Fowkes, Fakiha Siddiqui, Mark A. Ligocki, Tishya Indran, Kostantinos Konstantinidis, Bulent Kantarcioglu, Jin Shiomura, Bahare Fazeli, Chryssa Papageorgiou, Yongquan Gu, Anny Slama-Schwok, Eduardo Ramacciotti, Zenguo Zhai, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano = University of Milan (UNIMI), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sechenov First Moscow State Medical University, Campbell University [Buies Creek, NC, USA] (CU), University of Karachi, Heidelberg University, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Loyola University [Chicago], Cyprus Institute (CyI), University of Belgrade [Belgrade], Nuova Villa Claudia [Rome, Italy] (NVC), Universidad Católica San Antonio de Murcia (UCAM), Rambam Health Care Campus [Haifa, Israel], Technion - Israel Institute of Technology [Haifa], Ministry of Health of the Russian Federation (MHRF), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Trinity College Dublin, National and Kapodistrian University of Athens (NKUA), McMaster University [Hamilton, Ontario], Firestone Institute for Respiratory Health [Hamilton, ON, Canada] (FIRH), Ministry of Health [Saudi Arabia], Szent Imre Hospital [Budapest, Hungary] (SIH), Mashhad University of Medical Sciences, University of Edinburgh, Capital University of Medical Sciences [Beijing] (CUMS), Hôpitaux Universitaires de l'Est Parisien [Paris] (HUEP), Monash Medical Centre [Clayton, Australia], Central University of Tamil Nadu [Thiruvarur, India] (CUTN), Central University of Tamil Nadu (CUTN), Okmeydani Training and Research Hospital [Istanbul, Turkey] (OTRH), Centre International de Cancérologie de Dakar [Dakar, Senegal] (CICD), Aristotle University of Thessaloniki, University Hospital Southampton NHS Foundation Trust, Université Virtuelle du Sénégal [Dakar, Senegal] (UVS), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University Clinic of Hematology [Skopje, Republic of North Macedonia] (UCH), University of Medicine and Pharmacy [Cluj-Napoca, Romania] (UMP), Service d'Anesthésie réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Flor Ferenc Teaching Hospital [Kistarcsa, Hungary] (2FTH), San Camillo Forlanini Hospital [Rome], Loyola University Medical Center (LUMC), Science Valley Research Institute [São Paulo, Brazil] (SVRI), King Hussein Cancer Center [Amman, Jordan] (KH2C), CHU Fattouma Bourguiba [Monastir] (HFB), Medizinische Universität Wien = Medical University of Vienna, Nobelpharma Co. Ltd. [Tokyo, Japan], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), North Shore University Cardiologists [Skokie, Illinois, USA] (NSUC), American University of Beirut Faculty of Medicine and Medical Center (AUB), Klinikum Ernst von Bergmann [Potsdam, Germany] (KEVB), Peking University [Beijing], Chinese Academy of Medical Sciences [Beijing, China] (CAMS), Peking Union Medical College [Beijing, China], Université Mohammed V de Rabat [Agdal] (UM5), Scientific Reviewer Committee: Gregory Y H Lip, Michael Makris, Sam Schulman, Wolfgang Siess, Christian Weber, Sabbah, Michèle, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Milan, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and University of Mohammed V
Subjects: medicine.medical_specialty, Telemedicine, Economic growth, COVID-19 Vaccines, Population, Psychological intervention, Disease, 030204 cardiovascular system & hematology, Risk Assessment, Herd immunity, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Consensus Paper, Pandemic, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030212 general & internal medicine, Disease management (health), education, Pandemics, thrombosis, education.field_of_study, SARS-CoV-2, Immunization Programs, pandemic, Public health, COVID-19, Disease Management, health care systems, Hematology, 3. Good health, Public Health, Business
Abstract: Background One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. Management Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. Current Issues The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. Perspectives There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). Conclusion The “PDA strategy” integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.
Published: 2021

19. Antenatal Membranous Nephropathy and Type 2 (Axonal) Charcot-Marie-Tooth With Mutations in the Metallo-Membrane Endopeptidase Gene: A Call for Family Screening and Pharmacovigilance

Author: Hanna Debiec, Gauthier Remiche, Marina Vivarelli, Nicolette C. Notermans, Jeroen Nauta, Guilhem Solé, Paul Delrée, Pierre Ronco, Joëlle Nortier, Daria Diodato, Pediatrics, Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, University Medical Center [Utrecht], Bambino Gesù Children’s Hospital [Rome, Italy], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: peripheral neuropathy, Pharmacology, neprilysin, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Pharmacovigilance, Research Letter, medicine, 030212 general & internal medicine, Neprilysin, Gene, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, maternofetal allo-immunization, MME gene, membranous nephropathy, Généralités, medicine.disease, congenital nephropathy, neutral endopeptidase, Endopeptidase, 3. Good health, Peripheral neuropathy, Nephrology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

20. PHROG: families of prokaryotic virus proteins clustered using remote homology

Author: Rubén Enrique Pérez Bucio, Julien Lossouarn, Eric Olo Ndela, Clovis Galiez, François Enault, Robin Mom, Marie-Agnès Petit, Paul Terzian, Ariane Toussaint, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant (PIAF), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Université libre de Bruxelles (ULB), H2020 European Research Council685778INRAE, Statistique pour le Vivant et l’Homme (SVH), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Institut de Biologie et de Médecine Moléculaires [Gosselies] (ULB/IBMM), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB)
Subjects: AcademicSubjects/SCI01140, AcademicSubjects/SCI01060, Protein family, Viral protein, Ecology (disciplines), AcademicSubjects/SCI00030, Standard Article, Computational biology, Biology, AcademicSubjects/SCI01180, medicine.disease_cause, 03 medical and health sciences, Annotation, medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Homology (anthropology), Cluster analysis, 030304 developmental biology, Sequence (medicine), 0303 health sciences, prokaryotic virus proteins, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], MOBILE GENETIC ELEMENTS, 030302 biochemistry & molecular biology, homology, Classification, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, AcademicSubjects/SCI00980, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], PHROG, Reference genome
Abstract: Viruses are abundant, diverse and ancestral biological entities. Their diversity is high, both in terms of the number of different protein families encountered and in the sequence heterogeneity of each protein family. The recent increase in sequenced viral genomes constitutes a great opportunity to gain new insights into this diversity and consequently urges the development of annotation resources to help functional and comparative analysis. Here, we introduce PHROG (Prokaryotic Virus Remote Homologous Groups), a library of viral protein families generated using a new clustering approach based on remote homology detection by HMM profile-profile comparisons. Considering 17 473 reference (pro)viruses of prokaryotes, 868 340 of the total 938 864 proteins were grouped into 38 880 clusters that proved to be a 2-fold deeper clustering than using a classical strategy based on BLAST-like similarity searches, and yet to remain homogeneous. Manual inspection of similarities to various reference sequence databases led to the annotation of 5108 clusters (containing 50.6 % of the total protein dataset) with 705 different annotation terms, included in 9 functional categories, specifically designed for viruses. Hopefully, PHROG will be a useful tool to better annotate future prokaryotic viral sequences thus helping the scientific community to better understand the evolution and ecology of these entities.
Published: 2021

21. European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum: First Edition

Author: Ricard Navarro-Ripoll, Marc Vives, Steffen Rex, P. Matute, R. Peter Alston, Theofili Kousi, Simon J. Howell, Mona Momeni, Hossam El-Ashmawi, Fawzia Aboulfetouh, M. Granell, Aniruddha R. Janai, Gabor Erdoes, Caetano Nigro Neto, Alberto Hernandez Martinez, Sascha Treskatsch, Gianluca Paternoster, Theofani Antoniou, Anna Flo Forner, Kirstin Wilkinson, Giovanni Landoni, Joost M.A.A. van der Maaten, Joachim Erb, Philippe Gaudard, Philippe Burtin, E Schindler, Andrea Székely, Alain Vuylsteke, Laszlo L. Szegedi, Vera von Dossow, Jens Fassl, Chirojit Mukherjee, Mohamed R. El-Tahan, Fabio Guarracino, Dominique Bettex, Maria Benedetto, Dieter Van Beersel, Jan-Uwe Schreiber, Patrick Wouters, Dragana Unic-Stojanovic, Mansoura University [Egypt], University of Bern, University Medical Center Groningen [Groningen] (UMCG), University Hospital Southampton NHS Foundation Trust, Onassis Cardiac Surgery Center [Athens] (OCSC), Ruhr University Bochum (RUB), Instituto de Cardiologia Dante Pazzanese (IDPC), University Hospital Bonn, Semmelweis University [Budapest], University of Leipzig [Leipzig, Allemagne], University Department of Fundamental and Applied Medical Sciences and Clinical Department of Anesthesiology and Perioperative Medicine, Ghent, Belgium, Azienda Ospedaliera Universitaria Pisana, Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], University of Belgrade [Belgrade], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Hospital Clinic [Barcelona, Spain], Misr University for Science & Technology (MUST), Technische Universität Dresden = Dresden University of Technology (TU Dresden), University hospital of Zurich [Zurich], Sant'Orsola-Malpighi Hospital [Bologna, Italy], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Royal Infirmary of Edinburgh, IRCCS San Raffaele Scientific Institute [Milan, Italie], University General Hospital of Valencia, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité Campus Benjamin Franklin, University Hospitals Leuven [Leuven], Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., University of Leeds, Hospital Universitario de Bellvitge, University Hospital Basel [Basel], Hospital Dr Josep Trueta, Cairo University, Department of Anesthesia & Intensive Care, Helios Clinic for Cardiac Surgery, Karlsruhe, Germany., Hospital Clinico San Carlos, Hospital Clínico San Carlos, Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'anesthésiologie, El-Tahan, M. R., Erdoes, G., van der Maaten, J., Wilkinson, K., Kousi, T., Antoniou, T., von Dossow, V., Neto, C. N., Schindler, E., Szekely, A., Forner, A. F., Wouters, P. F., Guarracino, F., Burtin, P., Unic-Stojanovic, D., Schreiber, J. -U., Matute, P., Aboulfetouh, F., Navarro-Ripoll, R., Fassl, J., Bettex, D., Benedetto, M., Szegedi, L., Alston, R. P., Landoni, G., Granell, M., Gaudard, P., Treskatsch, S., Van Beersel, D., Vuylsteke, A., Howell, S., Janai, A. R., Martinez, A. H., Erb, J. M., Vives, M., El-Ashmawi, H., Rex, S., Mukherjee, C., Paternoster, G., Momeni, M., MUMC+: MA Anesthesiologie (9), and RS: MHeNs - R3 - Neuroscience
Subjects: medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], education, MEDLINE, Subspecialty, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Pediatric anesthesiology, Anesthesiology, Intensive care, Anesthesia, Cardiac Procedures, Medicine, Humans, Fellowships and Scholarships, 610 Medicine & health, Child, Curriculum, Cardiothoracic anesthesiology, business.industry, General surgery, 030208 emergency & critical care medicine, 3. Good health, Cardiac Anesthesia, Anesthesiology and Pain Medicine, Perioperative care, cardiovascular system, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Pediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers.
Published: 2021

22. Design and Evaluation of a Wireless Electrocardiogram Monitor in an Operating Room

Author: Ali Mansour, Philippe Aries, Benoit Clement, Ba Vinh Nguyen, Kahina Bensafia, Jean Louis Vincent, Department of Anesthesia and Intensive Care, Military Teaching Hospital 'Clermont Tonnerre', Brest, French, Pôle STIC_IDM, École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne), Lab-STICC_ENSTAB_CACS_COM, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Institut Mines-Télécom [Paris] (IMT)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-Institut Mines-Télécom [Paris] (IMT)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Lab-STICC_ENSTAB_CID_PRASYS, Department of Intensive Care, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Male, Operating Rooms, Time Factors, Action Potentials, Pilot Projects, Electromagnetic interference, law.invention, Bluetooth, Electrocardiography, 0302 clinical medicine, Heart Rate, 030202 anesthesiology, Electrosurgical unit, law, Materials Testing, Medicine, ST segment, Prospective Studies, Aged, 80 and over, Limits of agreement, Equipment Design, Middle Aged, Wireless Communications, Wireless Device, cardiovascular system, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Wireless Technology, circulatory and respiratory physiology, Adult, [SPI.AUTO]Engineering Sciences [physics]/Automatic, Young Adult, 03 medical and health sciences, QRS complex, Predictive Value of Tests, Monitoring, Intraoperative, Intensive care, Humans, Wireless, cardiovascular diseases, Simulation, Aged, business.industry, Intensive Care, Reproducibility of Results, Electrocardiogram ECG, Bluetooth technology, Anesthesiology and Pain Medicine, business, 030217 neurology & neurosurgery
Abstract: International audience; Wired electrocardiogram monitors are an important component of current perioperative monitoring. Wireless monitoring units could help reduce the number of cables attached to patients and thus improve anesthesia ergonomics and patient management. However, there is concern that electromagnetic interference generated by electrosurgical units may prevent effective wireless signals in the operating room. To evaluate the extent of this problem, we developed a Bluetooth electrocardiogram prototype monitor and compared its electrocardiogram traces to those captured with a standard wired electrocardiogram monitor in our operating room. METHODS: Bluetooth electrocardiogram and standard electrocardiogram traces captured from 10 patients undergoing surgical procedures that required use of an electrosurgical unit were compared by analysis of the durations of the P wave, QRS complex, and T wave and the position of the ST segment from the isoelectric line. The impact of the electrosurgical units on the Bluetooth electrocardiogram and S-electrocardiogram recordings was also assessed. RESULTS: There were no clinically relevant differences in P wave, QRS complex, or T-wave durations (0.006, 0.004, and 0.017 seconds, respectively) between Bluetooth electrocardiogram and standard electrocardiogram or in the position of the ST segment from the isoelectric line (0.02 mV). Mean differences were near zero, and Bland-Altman limits of agreement for individual differences were narrow (-0.035 to 0.047, -0.03 to 0.038, and -0.112 to 0.078 seconds for P wave, QRS complex, and T-wave durations, respectively, and -0.13 to 0.17 mV for ST segment position). Electrosurgical units use electrically disrupted Bluetooth electrocardiogram and standard electrocardiogram signals, but there was no electromagnetic interference effect on the Bluetooth electrocardiogram signals. CONCLUSIONS: Wireless electrocardiogram using Bluetooth can be reliably used in the operating room. The electrosurgical unit induces electric rather than electromagnetic artifacts, thus affecting wired and wireless electrocardiogram in a similar fashion.
Published: 2019

23. Direct admission to the intensive care unit from the emergency department and mortality in critically ill hematology patients

Author: Olivier Peyrony, Virginie Lemiale, Elie Azoulay, Dominique Benoit, Sylvie Chevret, Alexandre Demoule, Anne-Pascale Meert, Christine Lebert, Djamel Mokart, Adrien Mirouse, Achille Kouatchet, Pierre Perez, Martine Nyunga, Frédéric Pène, Fabrice Bruneel, Service des urgences, AP-HP Hôpital Saint-Louis, Service de biostatistiques et information médicale [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jules Bordet, Université Libre de Bruxelles [Bruxelles] (ULB), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Saint Louis [APHP], CHU Pitié-Salpêtrière [APHP], Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ghent University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, IMPACT, CANCER-PATIENTS, Critical Care and Intensive Care Medicine, Logistic regression, law.invention, 03 medical and health sciences, 0302 clinical medicine, Hematological malignancy, law, Anesthesiology, Epidemiology, Post-hoc analysis, Direct admission, medicine, Medicine and Health Sciences, EPIDEMIOLOGY, Intensive care unit, 030212 general & internal medicine, OUTCOMES, business.industry, Emergency department, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:RC86-88.9, 3. Good health, TIME, SEVERE SEPSIS, Propensity score matching, Emergency medicine, Economie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cohort study
Abstract: Background: The aim of this study was to assess the benefit of direct ICU admission from the emergency department (ED) compared to admission from wards, in patients with hematological malignancies requiring critical care. Methods: Post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICU in Belgium and France from January 2010 to May 2011. The variable of interest was a direct ICU admission from the ED and the outcome was in-hospital mortality. The association between the variable of interest and the outcome was assessed by multivariable logistic regression after multiple imputation of missing data. Several sensitivity analyses were performed: complete case analysis, propensity score matching and multivariable Cox proportional-hazards analysis of 90-day survival. Results: Direct ICU admission from the ED occurred in 266 (26.4%) cases, 84 of whom (31.6%) died in the hospital versus 311/742 (41.9%) in those who did not. After adjustment, direct ICU admission from the ED was associated with a decreased in-hospital mortality (adjusted OR: 0.63; 95% CI 0.45–0.88). This was confirmed in the complete cases analysis (adjusted OR: 0.64; 95% CI 0.45–0.92) as well as in terms of hazard of death within the 90 days after admission (adjusted HR: 0.77; 95% CI 0.60–0.99). By contrast, in the propensity score-matched sample of 402 patients, direct admission was not associated with in-hospital mortality (adjusted OR: 0.92; 95% CI 0.84–1.01). Conclusions: In this study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. Assessment of early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

24. Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications

Author: Mario Campone, Wilfried Gouraud, Hubert Hondermarck, Hamza Lasla, Andrea Gombos, Florence Dalenc, Pascal Jézéquel, Olivier Kerdraon, Jean-Luc Canon, Suzette Delaloge, Catherine Guérin-Charbonnel, Véronique Verriele, Delphine Loussouarn, Jérôme Lemonnier, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Unité Mixte de Génomique du Cancer [ICO, Saint Herblain] (Site René Gauducheau), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Hôpital Laennec, Unité de bioinfomique [ICO, Saint Herblain], UNICANCER-UNICANCER, Laboratoire d’Anatomie et Cytologie Pathologiques [ICO, Saint Herblain], School of Biomedical Sciences and Pharmacy [Callaghan, Australia], University of Newcastle [Australia] (UoN)-Hunter Medical Research Institute [Callaghan, Australia], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Département Oncologie Médicale [Bruxelles, Belgium], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Département d'Oncologie Médicale [CHU Toulouse] (IUCT Oncopole - Institut Universitaire du Cancer), Centre hospitalier universitaire de Toulouse - CHU Toulouse-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-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)-CHU Toulouse [Toulouse]-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), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), French Breast Cancer Intergroup - UCBG [Paris] (R&D UNICANCER), R&D Unicancer [Paris], Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Part of this study was funded by Comité Féminin 49., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), and Bernardo, Elizabeth
Subjects: Molecular subtypes, Lymphocyte, Neurogenesis, Triple Negative Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Plasma cell, Biology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Cluster Analysis, Humans, Metabolomics, Transcriptomics, Immunome, B cell, Triple-negative breast cancer, Neoplasm Staging, Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, Acquired immune system, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Immune checkpoint, Tumor Burden, 3. Good health, Gene expression profiling, Cancérologie, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Triple-negative, Female, Neoplasm Grading, Transcriptome, Tertiary lymphoid structures, Research Article
Abstract: Background: Heterogeneity and lack of targeted therapies represent the two main impediments to precision treatment of triple-negative breast cancer (TNBC), and therefore, molecular subtyping and identification of therapeutic pathways are required to optimize medical care. The aim of the present study was to define robust TNBC subtypes with clinical relevance. Methods: Gene expression profiling by means of DNA chips was conducted in an internal TNBC cohort composed of 238 patients. In addition, external data (n = 257), obtained by using the same DNA chip, were used for validation. Fuzzy clustering was followed by functional annotation of the clusters. Immunohistochemistry was used to confirm transcriptomics results: CD138 and CD20 were used to test for plasma cell and B lymphocyte infiltrations, respectively; MECA79 and CD31 for tertiary lymphoid structures; and UCHL1/PGP9.5 and S100 for neurogenesis. Results: We identified three molecular clusters within TNBC: one molecular apocrine (C1) and two basal-like-enriched (C2 and C3). C2 presented pro-tumorigenic immune response (immune suppressive), high neurogenesis (nerve infiltration), and high biological aggressiveness. In contrast, C3 exhibited adaptive immune response associated with complete B cell differentiation that occurs in tertiary lymphoid structures, and immune checkpoint upregulation. External cohort subtyping by means of the same approach proved the robustness of these results. Furthermore, plasma cell and B lymphocyte infiltrates, tertiary lymphoid structures, and neurogenesis were validated at the protein levels by means of histological evaluation and immunohistochemistry. Conclusion: Our work showed that TNBC can be subcategorized in three different subtypes characterized by marked biological features, some of which could be targeted by specific therapies., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

25. Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Author: Richard Iggo, Jean-Michel Picquenot, Denis Larsimont, Véronique Becette, Jonas Bergh, Gaëtan MacGrogan, Jeremy Thomas, Olivier Kerdraon, Leen Slaets, David Cameron, Fanny Pommeret, C. Poncet, Jean-Christophe Tille, Frédéric Bibeau, Hervé Bonnefoi, Alexandre Bodmer, Jean-Pierre Ghnassia, Thomas Grellety, Donnat, Martin, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie, UNICANCER-UNICANCER, UNICANCER, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital René HUGUENIN (Saint-Cloud), Centre René Gauducheau, CRLCC René Gauducheau, 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), Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Hôpitaux Universitaires de Genève (HUG), Department of Oncology-Pathology [Karolinska Institutet], Karolinska Institutet [Stockholm], Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and Swiss Group for Clinical Cancer Research (SAKK)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Concordance, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ddc:616.07, Disease-Free Survival, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Chemotherapy, business.industry, Gene Expression Profiling, Apocrine, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, Cancérologie, ErbB Receptors, Survival Rate, Clinical trial, Biological sciences, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, Receptors, Androgen, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Receptors, Progesterone, business
Abstract: Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

26. The circular RNome of primary breast cancer

Author: Steven Van Laere, Colin A. Purdie, John A. Foekens, Gaëten MacGrogan, Marcel Smid, Andrew Futreal, Vanja de Weerd, Paul N. Span, Marc J. van de Vijver, Jorunn E. Eyfjord, Serena Nik-Zainal, F. Germán Rodríguez-González, Roberto Salgado, Peter T. Simpson, Christine Desmedt, Wendy J. C. Prager-van der Smissen, Fred C.G.J. Sweep, Tari A. King, Adam Butler, Michael R. Stratton, Carlos Caldas, Gert Van den Eynden, Sunil R. Lakhani, Saskia M. Wilting, Alastair M. Thompson, Angelo Paradiso, John W.M. Martens, Anne Vincent-Salomon, Johan Staaf, Anne van Galen, Sancha Martin, Hendrik G. Stunnenberg, Annegien Broeks, Andrea L. Richardson, Anne Lise Børresen-Dale, Helen Davies, Michelle van der Vlugt-Daane, Katharina Uhr, Stian Knappskog, Alain Viari, Anieta M. Sieuwerts, Medical Oncology, Smid, Marcel [0000-0003-0605-1901], Apollo - University of Cambridge Repository, Pathology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Dana-Farber Cancer Institute [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut Bergonié [Bordeaux], UNICANCER, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Department of Pathology [Dundee], Ninewells Hospital and Medical School [Dundee], Radboud University Medical Center [Nijmegen], University of Southern Queensland (USQ), University of Antwerp (UA), Istituto Tumori 'Giovanni Paolo II' [Bari], University of Iceland [Reykjavik], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), The University of Texas M.D. Anderson Cancer Center [Houston], University of Bergen (UiB), Haukeland University Hospital, Memorial Sloane Kettering Cancer Center [New York], Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], Fondation Synergie Lyon Cancer [Lyon], Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: Génétique clinique, Proliferation index, [SDV]Life Sciences [q-bio], Transcriptome, Exon, Breast cancer, 0302 clinical medicine, Brjóstakrabbamein, MUTATIONAL PROCESSES, Genetics (clinical), Genetics & Heredity, 0303 health sciences, Gene knockdown, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], ABUNDANT, CREB-Binding Protein, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, GENOME, Chemistry, Lymphatic Metastasis, RNA splicing, MCF-7 Cells, Female, Engineering sciences. Technology, Biologie, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Breast Neoplasms, Biology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, REVEALS, Biomarkers, Tumor, Genetics, medicine, Erfðafræði, Humans, TAMOXIFEN, Molecular Biology, Gene, SIGNATURES, 030304 developmental biology, Science & Technology, LANDSCAPE, Research, MICRORNA, Cancer, RNA, Circular, medicine.disease, DNA-rannsóknir, GENE, RNAs, Repressor Proteins, Biotechnology & Applied Microbiology, Cancer research, RNA, Human medicine, Carrier Proteins, 030217 neurology & neurosurgery
Abstract: Publisher's version (útgefin grein), Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer., We thank the Erasmus MC Cancer Computational Biology Center for giving access to their IT infrastructure and the software that was used for the computations and data analysis in this study. We thank Sandra Albassam for her help with the first versions of the script to identify circular regions. We thank Maurice P.H.M. Jansen, Jean C. Helmijr, Inge de Kruijff, and Manouk K. Bos for their help in evaluating plasma samples that were gathered in the EU-FP7 CareMore (nr 601760) project. We thank for technical support Miriam Ragle Aure and Anita Langerød of the Oslo University Hospital, Norway; Ewan Birney of the European Bioinformatics Institute, UK; and Stefania Tommasi of the IRCCS Istituto Tumori “Giovanni Paolo II,” Bari, Italy. We thank the Oslo Breast Cancer Research Consortium (OSBREAC), Norway (https://www.ous-research.no/home/kgjebsen/home/14105) for contributing patient samples and Sabine Linn and Marleen Kok of The Netherlands Cancer Institute for contributing samples for the AI cohort. Finally, we thank all members of the ICGC Breast Cancer Working Group. This work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (a European research project funded by the European Community’s Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006) and the Triple Negative project funded by the Wellcome Trust (grant reference 077012/Z/05/Z). F.G.R.-G. and S.M. were funded by BASIS. J.A.F. was funded through an ERC Advanced Grant (ERC-2012-AdG-322737) and ERC Proof-of-Concept Grant (ERC-2017-PoC-767854). K.U. was funded by the Daniel den Hoed Foundation. S.N.-Z. is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (WT100183MA). A.L.R. is partially supported by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (NIH/NCI 5 P50 CA16 8504-02). A.M.S. was supported by Cancer Genomics Netherlands (CGC.nl) through a grant from the Netherlands Organization of Scientific research (NWO). M. Smid was supported by the EU-FP7-DDR response project. C.D. was supported by a grant from the Breast Cancer Research Foundation. J.E. was funded by The Icelandic Centre for Research (RANNIS).
Published: 2019

27. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma

Author: Philippe Moreau, Laurent Garderet, Bertrand Arnulf, Sabrina Maheo, Lotfi Benboubker, Mamoun Dib, Sabine Brechignac, Nelly Robillard, Mohamad Mohty, Margaret Macro, Brigitte Pegourie, Thierry Facon, Brigitte Kolb, Karim Belhadj, Nikhil C. Munshi, Bruno Royer, Olivier Decaux, Arnaud Jaccard, Valérie Lauwers-Cances, Marie-Lorraine Chretien, Anne-Marie Stoppa, Hervé Avet-Loiseau, Xavier Leleu, Kenneth C. Anderson, Jean-Richard Eveillard, Martin Moorhead, Chantal Doyen, Cecile Fohrer, Lionel Karlin, Jill Corre, Victoria Carlton, Paul G. Richardson, Malek Faham, Jean-Luc Harousseau, Michel Attal, Nathalie Meuleman, Thomas D. Willis, Aurore Perrot, Cyrille Hulin, Thomas Dejoie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), 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 National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Biochimie [Nantes], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire de Bobigny, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-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 de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Universitaire de Caen, Department of Energy / Joint Genome Institute (DOE), Los Alamos National Laboratory (LANL), Département d'Hématologie Clinique [CHU Nantes], Département d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d'Hématologie [CHU Nantes], Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hématologie [IUCT Oncopole, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Département d'hématologie [CHU Saint-Antoine, AP-HP], AP-HP - Hôpital Saint-Antoine, Institut Jules Bordet, Service hématologie (CHU d'Amiens), Département d'Hématologie Clinique [CHU Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service d'Hématologie [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Oncology, Neoplasm, Residual, Biochemistry, Dexamethasone, Bortezomib, Observations Lymphoid Neoplasia, 0302 clinical medicine, Maintenance therapy, Bone Marrow, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Lenalidomide, Multiple myeloma, Lymphoid Neoplasia, Hazard ratio, High-Throughput Nucleotide Sequencing, Hematology, Minimal Residual Disease Negativity, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, medicine.drug, medicine.medical_specialty, Plasma Cells, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Humans, Clinical Trials, Survival rate, Aged, business.industry, Cell Biology, medicine.disease, Minimal residual disease, Transplantation, 030104 developmental biology, business, Follow-Up Studies
Abstract: IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (
Published: 2018

28. Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis

Author: Elisa Agostinetto, Evandro de Azambuja, Nina Radosevic-Robin, Maria Alice Franzoi, Roberto Salgado, Rafael Caparica, Marcello Ceppi, Karen Willard-Gallo, Sherene Loi, Frédérique Penault-Llorca, Marco Bruzzone, Université libre de Bruxelles (ULB), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Peter MacCallum Cancer Centre [Melbourne, Australie], and COLO, Mouniati
Subjects: Oncology, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], “Local recurrence”, Breast Neoplasms, Triple Negative Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Lymphocytes, Tumor-Infiltrating, Internal medicine, “Tumour infiltrating lymphocytes”, Medicine, Humans, 030212 general & internal medicine, Chirurgie, RC254-282, ComputingMilieux_MISCELLANEOUS, “Non-invasive breast cancer”, business.industry, Carcinoma in situ, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, General Medicine, Odds ratio, medicine.disease, Prognosis, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Meta-analysis, Biomarker (medicine), Surgery, Female, Original Article, Neoplasm Recurrence, Local, business
Abstract: Background: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. Methods: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. Results: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03–4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49–0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23–6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93–7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69–7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33–4.10; p < 0.001). Conclusions: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

29. Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

Author: Françoise Helmbacher, Jose Jf Millan-Cayetano, Ievgenia Pastushenko, L. Ríos-Buceta, Benjamin Swedlund, Alicia Perez-Bustillo, Magdalena De Troya, Delphi Van Haver, Sergio Hassid, Francis Impens, Bob Meeusen, Sophie Lemaire, Yura Song, Christine Decaestecker, Gaëlle Lapouge, Ramon Sieira-Gil, Cédric Balsat, David Perez-Morga, Beatriz Agreda-Moreno, Cédric Blanpain, Pedro Redondo, Matthieu Opitz, Youri Sokolow, Isabelle Salmon, Christos Sotiriou, Onofre Sanmatrtin, Frédérique De Cock, Virginie Moers, Samuel Scozzaro, Marjorie Vermeersch, Pedro Jaén, Yacine Bareche, Christine Dubois, Milena Rozzi, Nicky D'Haene, Manuel Théry, Yves-Remi Van Eycke, Jeremy Blondeau, Veerle Janssens, Federico Mauri, Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium., Dermatology Department, Cliniques de l'Europe, Brussels, Belgium, Université libre de Bruxelles (ULB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Cancer Institute (LKI), Leuven, Belgium, VIB-UGent Center for Medical Biotechnology, VIB Proteomics Core, Ghent, Belgium, Universiteit Gent = Ghent University (UGENT), VIB proteomic core, Ghent, Belgium, Alvéole, Paris, France., CytoMorphoLab UMR976 HIPI, CEA, INSERM, Université de Paris, Paris, France, CytoMorphoLab, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Ecole Polytechnique de Bruxelles, Department of Dermatology, Complejo Asistencial Universitario de León, León, Spain, Department of Otolaryngology - Head and Neck Surgery, Hospital Clinico 'Lozano Blesa', Zaragoza, Spain, Dermatology Department, Ramón y Cajal Hospital, Madrid, Spain, University of Alcalá, Madrid, Spain, Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Department of Dermatology, Clinica Universidad de Navarra, Navarra, Spain, Department of Maxillofacial Surgery, Head and Neck Surgery, Hospital Clínic, Barcelona, Spain, Department of Dermatology, Hospital Costa del Sol, Marbella, Spain, Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain, Pathology Department, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), WELBIO, Université Libre de Bruxelles (ULB), Brussels, Belgium, Walloon excellence in life sciences and biotechnology (WELBIO), Fonds de la Recherche Scientifique (FNRS), European Regional Development Fund, Walloon Region, Televie (Charity Association), European Research Council, Fond Erasme, Fondation Contre le Cancer, ULB Foundation, Worldwide Cancer Research, Foundation Baillet Latour, Helmbacher, Francoise, Dermatology Department, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium, Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium, VIB Center for Medical Biotechnology, Ghent, Belgium, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium, Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium., Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB), Charleroi, Belgium, DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), Charleroi, Belgium, Laboratory of Image Synthesis and Analysis, Ecole Polytechnique de Bruxelles, Université Libre de Bruxelles (ULB), Brussels, Belgium, Department of Thoracic Surgery, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium, Department of Otolaryngology - Head and Neck Surgery, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium, and Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
Subjects: 0301 basic medicine, Proteomics, Lung Neoplasms, Skin Neoplasms, [SDV]Life Sciences [q-bio], Cell, Metastasis, Mesoderm, Mice, 0302 clinical medicine, Neoplasms, Neoplasm Metastasis, YAP1, Regulation of gene expression, Multidisciplinary, EZH2, Cadherins, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Hyaluronan Receptors, Phenotype, src-Family Kinases, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Disease Progression, Neoplastic Stem Cells, FAT1, Signal Transduction, Epithelial-Mesenchymal Transition, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, 03 medical and health sciences, SOX2, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Skin Squamous Cell Carcinoma, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Adaptor Proteins, Signal Transducing, SOXB1 Transcription Factors, Médecine pathologie humaine, Biologie moléculaire, Zinc Finger E-box-Binding Homeobox 1, Epithelial Cells, YAP-Signaling Proteins, medicine.disease, Phosphoproteins, Cancérologie, 030104 developmental biology, Cancer research, Biologie cellulaire, Gene Deletion, Transcription Factors
Abstract: FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state., info:eu-repo/semantics/published
Published: 2021

30. The IBD-disk is a reliable tool to assess the daily-life burden of patients with inflammatory bowel disease

Author: Tadbiri, Sara, Nachury, Maria, Bouhnik, Yoram, Serrero, Melanie, Hébuterne, Xavier, Roblin, Xavier, Kirchgesner, Julien, Bouguen, Guillaume, Franchimont, Denis, Savoye, Guillaume, Buisson, Anthony, Louis, Edouard, Nancey, Stephane, ABitbol, Vered, Reimund, Jean-Marie, DeWit, Olivier, Vuitton, Lucine, Matthieu, Nicolas, Peyrin-Biroulet, Laurent, Gilletta, Cyrielle, Allez, Matthieu, Viennot, Stephanie, Trang-Poisson, Caroline, Dib, Nina, Brixi, Hedia, Boualit, Medina, Plastaras, Laurianne, Boivineau, Lucile, Fumery, Mathurin, Caillo, Ludovic, Laharie, David, Amiot, Aurelien, GETAID-IBD-disk study group, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Liège (CHU-Liège), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier [Valenciennes, Nord], Hôpital pasteur [Colmar], Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by Abbvie, CHU Saint-Etienne, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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), Jonchère, Laurent, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université de Montpellier (UM)-CHU Saint-Eloi, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Visual analogue scale, [SDV]Life Sciences [q-bio], Population, Disease, patient-reported outcome, Inflammatory bowel disease, digestive system, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Belgium, inflammatory bowel disease, Internal medicine, Medicine, Humans, education, Irritable bowel syndrome, ulcerative colitis, education.field_of_study, Crohn's disease, business.industry, Gastroenterology, General Medicine, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, disability, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Patient-reported outcome, Female, France, business
Abstract: Background and Aim The inflammatory bowel disease [IBD]-disk is a 10-item self-questionnaire that is used to assess IBD-related disability. The aim of the present study was to evaluate this tool in the assessment of IBD daily-life burden. Methods A 1-week cross-sectional study was conducted in 42 centres affiliated in France and Belgium. Patients were asked to complete the IBD-disk [best score: 0, worst score: 100] and a visual analogue scale [VAS] of IBD daily-life burden [best score: 0, worst score: 10]. Analyses included internal consistency, correlation analysis, and diagnostic performance assessment. Results Among the 2011 IBD outpatients who responded to the survey [67.8% of the patients had Crohn’s disease], 49.9% were in clinical remission. The IBD-disk completion rate was 73.8%. The final analysis was conducted in this population [n = 1455 patients]. The mean IBD-disk score and IBD daily-life burden VAS were 39.0 ± 23.2 and 5.2 ± 2.9, respectively. The IBD-disk score was well correlated with the IBD daily-life burden VAS [r = 0.67; p 5] was 0.81 (95% confidence interval [CI]: 0.79–0.83; p Conclusions In a large cohort of patients, the IBD-disk score was well correlated with IBD daily-life burden, and it could be used in clinical practice.
Published: 2021

31. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19

Author: Lionel Piroth, Bruno Mourvillier, Joy Mootien, François-Xavier Lescure, Emmanuel Faure, S. Gallien, Dominique Costagliola, Jean-Christophe Richard, Noemie Mercier, Florent Wallet, Yazdan Yazdanpanah, Marion Noret, Claire Andrejak, Jean-Philippe Lanoix, Julien Poissy, Johan Courjon, Saad Nseir, François Danion, Violaine Tolsma, Alain Makinson, Odile Launay, Raphaël Clere-Jehl, Bruno Lina, Drifa Belhadi, Valérie Pourcher, Antoine Kimmoun, Karine Lacombe, Juliette Saillard, Maude Bouscambert-Duchamp, Stéphane Jauréguiberry, Charles Burdet, Toni Alfaiate, Olivier Epaulard, Minh Patrick Lê, Gilles Peytavin, Elisabeth Botelho-Nevers, Thérèse Staub, Guillaume Martin-Blondel, Alpha Diallo, Lila Bouadma, Aline Dechanet, François Goehringer, Florence Ader, Nathan Peiffer-Smadja, Jean-Christophe Navellou, Christelle Delmas, Rostane Gaci, Kevin Bouiller, Maya Hites, André Cabié, Jean Reuter, Sylvie Leroy, Axelle Dupont, François Raffi, Amandine Gagneux-Brunon, Jean Reignier, Clément Dubost, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, National Institute for Health Research [Cambridge, UK], Imperial College London, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille, Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Institut de Santé Publique, Université de Médecine Carol Davila, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Réanimation Médicale [CHRU Nancy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Les Hôpitaux Universitaires de Strasbourg (HUS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), 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 Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Etablissement français du don du sang [Montpellier], CHU de la Martinique [Fort de France], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université de Paris (UP), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-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), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Université Lille Nord de France (COMUE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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 National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Physiopathologie et biothérapies des infections muqueuses (GIMAP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération d’Infectiologie Multidisciplinaire de l’Arc Alpin [CHU Grenoble-Alpes], Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Institut des Agents Infectieux [Lyon] (IAI), Réseau national de recherche clinique en infectiologie (RENARCI), CHU Amiens-Picardie, Université libre de Bruxelles (ULB), École normale supérieure - Lyon (ENS 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Lorraine (UL), Hôpital Bicêtre, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Lille, Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), CHU Grenoble, Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université 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)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Chrono-environnement (UMR 6249) (LCE), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), 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), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Montpellier 1 (UM1)-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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Lopinavir/ritonavir, law.invention, 0302 clinical medicine, Randomized controlled trial, law, immune system diseases, MESH: Antiviral Agents* / therapeutic use, 030212 general & internal medicine, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, virus diseases, Lopinavir, General Medicine, MESH: Lopinavir / therapeutic use, 3. Good health, Infectious Diseases, MESH: Interferon beta-1a / therapeutic use, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pharmaceutical Preparations, MESH: Hydroxychloroquine / therapeutic use, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, medicine.drug, Hydroxychloroquine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Antiviral Agents, 03 medical and health sciences, Interferon β-1a, Internal medicine, medicine, Humans, education, Adverse effect, MESH: COVID-19* / drug therapy, MESH: Drug Combinations, MESH: Humans, business.industry, SARS-CoV-2, Drug Repositioning, Interferon beta-1a, COVID-19, MESH: Adult, MESH: Male, MESH: Ritonavir / therapeutic use, Ritonavir, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
Published: 2021

32. Thrombectomy for Basilar Artery Occlusion with Mild Symptoms

Author: Adrien Guenego, Cyril Dargazanli, David Weisenburger-Lile, Benjamin Gory, Sébastien Richard, Célina Ducroux, Michel Piotin, Raphael Blanc, Julien Labreuche, Ludovic Lucas, Mathilde Aubertin, Amel Benali, Romain Bourcier, Lili Detraz, Stéphane Vannier, Maud Guillen, François Eugene, Gregory Walker, Ronda Lun, Arturo Consoli, Bertrand Lapergue, Robert Fahed, Hocine Redjem, Simon Escalard, Jean-Philippe Desilles, Gabriele Ciccio, Stanislas Smajda, Benjamin Maier, Solene Hebert, François Delvoye, Mikael Mazighi, Mikael Obadia, Candice Sabben, Roxanne Peres, Ovide Corabianu, Thomas de Broucker, Didier Smadja, Sonia Alamowitch, Olivier Ille, Eric Manchon, Pierre-Yves Garcia, Guillaume Taylor, Malek Ben Maacha, Adrien Wang, Serge Evrard, Maya Tchikviladze, Nadia Ajili, David Weisenburger, Lucas Gorza, Géraldine Buard, Oguzhan Coskun, Federico Di Maria, Georges Rodesh, Sergio Zimatore, Morgan Leguen, Julie Gratieux, Fernando Pico, Haja Rakotoharinandrasana, Philippe Tassan, Roxanna Poll, Sylvie Marinier, Gaultier Marnat, Florent Gariel, Xavier Barreau, Jérôme Berge, Louis Veunac, Patrice Menegon, Igor Sibon, Stéphane Olindo, Pauline Renou, Sharmila Sagnier, Mathilde Poli, Sabrina Debruxelles, Benjamin Daumas-Duport, Pierre-Louis Alexandre, Monica Roy, Cédric Lenoble, Vincent L'allinec, Jean-Baptiste Girot, Hubert Desal, Serge Bracard, René Anxionnat, Marc Braun, Anne-Laure Derelle, Romain Tonnelet, Liang Liao, François Zhu, Emmanuelle Schmitt, Sophie Planel, Lisa Humbertjean, Gioia Mione, Jean-Christophe Lacour, Mathieu Bonnerot, Nolwenn Riou-Comte, Vincent Costalat, Caroline Arquizan, Grégory Gascou, Pierre-Henri Lefèvre, Imad Derraz, Carlos Riquelme, Nicolas Gaillard, Isabelle Mourand, Lucas Corti, Eugene François, Jean-Christophe Ferre, Helene Raoult, Thomas Ronziere, Maria Lassale, Christophe Paya, Jean-Yves Gauvrit, Clément Tracol, Sophie Langnier-Lemercier, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Foch [Suresnes], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Pontchaillou [Rennes], The Ottawa Hospital, Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Gui de Chauliac [Montpellier], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Risk Factors, Internal medicine, medicine, Vertebrobasilar Insufficiency, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, In patient, cardiovascular diseases, Prospective cohort study, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Ischemic Stroke, Retrospective Studies, Thrombectomy, Stroke scale, business.industry, Basilar artery occlusion, Middle Aged, medicine.disease, nervous system diseases, 3. Good health, Mild symptoms, Treatment Outcome, 030220 oncology & carcinogenesis, Cardiology, Surgery, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: To evaluate outcomes of thrombectomy in patients with a basilar artery occlusion (BAO) and mild symptoms, defined by an initial National Institutes of Health Stroke Scale (NIHSS) score ≤6.We performed a retrospective analysis of a multicenter prospective cohort of consecutive patients with acute ischemic stroke with BAO who underwent thrombectomy. We compared baseline and procedural characteristics, as well as outcomes between patients with BAO with an NIHSS score ≤6 and6. Multivariate analyses were performed to determine baseline and procedural predictors of good outcome (modified Rankin Scale score 0-2) among patients with an NIHSS score ≤6.A total of 269 patients were included: 50 (19%) had an initial NIHSS score ≤6 and 219 (81%) had an NIHSS score6. Patients with mild strokes (NIHSS score ≤6) had better outcomes (68% of modified Rankin Scale score 0-2 vs. 27% for NIHSS score6; P0.0001), lower mortality (14% vs. 48; P0.0001) and fewer parenchymal hematomas at day 1 (0% vs. 10%; P = 0.016). A multivariate analysis identified the following predictors for good outcome among patients with BAO with an NIHSS score ≤6: younger age, fewer passes, a cardioembolic cause, and the absence of need for angioplasty/stenting.Thrombectomy seems to be safer and more effective for mild BAO strokes with NIHSS score ≤6 than for more severe patients. Even although thrombectomy showed high rates of recanalization, a substantial proportion (32%) nevertheless had a poor long-term clinical outcome. The number of passes, patient's age, and stroke cause seem to be predictors of clinical outcome.
Published: 2021

33. Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma

Author: Marie Maerevoet, Jm Schiano, Bénédicte Deau, Mg Silva, Apasia Stamatoullas, Roch Houot, Guillaume Manson, Pauline Brice, Laurent Dercle, Herve Ghesquieres, Carmelo Carlo-Stella, Juliette Bouteloup, Kamal Bouabdallah, Charles Herbaux, Florence Poizeau, E. Nicolas-Virelizier, M. de Charette, Chloe Antier, CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto Português de Oncologia de Lisboa Francisco Gentil, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre Hospitalier Chalon-sur-Saône William Morey, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre hospitalier universitaire de Nantes (CHU Nantes), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Humanitas University [Milan] (Hunimed), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Gustave Roussy (IGR), Columbia University Medical Center (CUMC), Columbia University [New York], and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: medicine.medical_specialty, Training set, business.industry, [SDV]Life Sciences [q-bio], Specific time, General Medicine, 3. Good health, 030218 nuclear medicine & medical imaging, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Refractory Hodgkin Lymphoma, Medicine, Hodgkin lymphoma, Radiology, Nuclear Medicine and imaging, In patient, Immunotherapy, Relapse risk, business, Anti pd1, Biomarkers, Checkpoint inhibitors
Abstract: International audience; Introduction - Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods - We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results - Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion - In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.
Published: 2021

34. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author: Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract: International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.
Published: 2021

35. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Author: Jean-François Emile, Jean-Luc Van Laethem, Jérôme Torrisani, Pieter Demetter, Yuna Blum, Anne Couvelard, Pascal Hammel, Armelle Bardier-Dupas, Francesco Puleo, Miroslaw Radman, Jérôme Cros, Magali Svrcek, Rémy Nicolle, Jerome Raffenne, Valérie Paradis, Fernando Ariel Martin, Marina Konta, Jean-Baptiste Bachet, Vinciane Rebours, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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 National de la Recherche Scientifique (CNRS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], 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), Hôpital Ambroise Paré [AP-HP], Hôpital Erasme [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Cancer Research, DNA repair, [SDV]Life Sciences [q-bio], Young patients, Biology, elderly patients, Multi‐omics, lcsh:RC254-282, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine, Epigenomics, Two-dimensional gel electrophoresis, PDAC, Methylation, Sciences bio-médicales et agricoles, multi-omics, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV] Life Sciences [q-bio], Cancérologie, Elderly patients, young patients, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Proteome, Cancer research, Adenocarcinoma
Abstract: Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late‐onset tumors (LOT) have been described, little is known about early‐onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation‐related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age‐related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age‐related differences were more preeminent in non‐tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multiomics comparison showed that EOT harbor a comparable molecular profile to that of LOT., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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36. Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study

Author: Olivier Le Moine, Pascal Le Corre, Gwenolé Loas, Gil Darquennes, Université libre de Bruxelles (ULB), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], functional inhibitors of acid sphingomyelinase (FIASMAs), COVID-19, lcsh:Medicine, lcsh:RS1-441, Pharmaceutical Science, Disease, amlodipine, Logistic regression, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Drug Discovery, Medicine, Amlodipine, Mortality, Medical prescription, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, lcsh:R, Biologie moléculaire, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Obesity, mortality, 3. Good health, [SDV] Life Sciences [q-bio], functional inhibitors of acid sphingomyelinase (FIASMAs), Functional inhibitors of acid sphingomyelinase (FIASMAs), COVID-19, Molecular Medicine, Sciences pharmaceutiques, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21–96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02–1.07, p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03–4.22, p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27–1.04, p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02–1.07, p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33–5.79, p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23–5.97, p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09–0.62, p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.
Published: 2021

37. Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?

Author: Gwenolé Loas, Pascal Le Corre, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), No funding, Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: in vitro and in silico, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, [SDV]Life Sciences [q-bio], repurposing, Bioinformatics, 030226 pharmacology & pharmacy, SARS‐CoV‐2, Virus, FIASMA, ABCB1 transporter, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, functional inhibitors of acid sphingomyelinase, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, acid sphingomyelinase, Repurposing, Pharmacology, business.industry, SARS-CoV-2, Drug Repositioning, COVID-19 Drug Treatment, 3. Good health, [SDV] Life Sciences [q-bio], Drug repositioning, Sphingomyelin Phosphodiesterase, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, antiviral activity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Acid sphingomyelinase, business, medicine.drug
Abstract: What is known and objective Infection by SARS‐CoV‐2, the virus responsible of COVID‐19, is associated with limited treatment options. The purpose of this study was to evaluate the rationale for repurposing functional inhibitors of acid sphingomyelinase (FIASMAs), several of which are approved medicines, for the treatment of SAR‐CoV‐2 infections. Comment We propose and discuss the FIASMAs’ lysosomotropism as a possible explanation for their observed in vitro activities against viruses, and more specifically against infections caused by coronaviruses such as SARS‐CoV‐2. Successful in vitro‐to‐in vivo translation of FIASMAs requires that their pharmacokinetics (dosing regimen and drug‐drug interactions) are matched with viral kinetics. What is new and conclusion Drug repurposing to ensure rapid patient access to effective treatment has garnered much attention in this era of the COVID‐19 pandemic. The observed lysosomotropic activity of small‐molecule FIASMA compounds suggests that their repurposing as potential drugs against SARS‐CoV‐2 is promising., FIASMA are cationic drugs with lipophilic properties that diffuse in the lysosome by passive diffusion and potentially by using ABCB1 transporter located onto the lysosomal membrane. This diffusion increases the intra‐lysosomal pH so that acid sphingomyelinase (ASM) is detached from the inner leaflet of the lysosomal membrane, and is further degraded by proteolysis. Hence, ASM translocation is no longer effective and the formation of lipid rafts on the cell membrane is altered. These membrane modifications impair the different mechanisms of internalization (i.e., fusion and entry) used by viruses such as SARS‐CoV‐2 to penetrate in the cytosol of cells.
Published: 2021

38. Improving generalization in MR‐to‐CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data

Author: David Pasquier, Nick Reynaert, John Klein, Kévin Brou Boni, Akos Gulyban, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Lille-UNICANCER
Subjects: Computer science, Generalization, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Text mining, Histogram, Hounsfield scale, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Unpaired Data, business.industry, Deep learning, Radiotherapy Planning, Computer-Assisted, Pattern recognition, Radiotherapy Dosage, General Medicine, Magnetic Resonance Imaging, Radiation therapy, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Artificial intelligence, Radiotherapy, Intensity-Modulated, business, Tomography, X-Ray Computed, Generative adversarial network, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an]
Abstract: PURPOSE MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data. MATERIALS AND METHODS This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis. RESULTS The mean MAEs were 59.8 Hounsfield units ( HU ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was 1.2% with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s. CONCLUSION This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.
Published: 2021

39. Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen

Author: Marco Mariotti, Benjamin Beck, Eric Gilson, Vadim N. Gladyshev, Doria Filipponi, Mélanie Pousse, Adeline Augereau, Frédérick Libert, Vera Gorbunova, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Rochester [USA], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, I.R.I.B.H.M., Université libre de Bruxelles (ULB), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and augereau, adeline
Subjects: Rodent, [SDV]Life Sciences [q-bio], Mutant, 03 medical and health sciences, 0302 clinical medicine, Rates, biology.animal, medicine, Glycolysis, Càncer, Research Articles, Naked mole-rat, Cancer, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, biology, Chemistry, SciAdv r-articles, Life Sciences, Généralités, Cell Biology, Oxigen, Hypoxia (medical), biology.organism_classification, Rats, Cell biology, Amino acid, Telomere, [SDV] Life Sciences [q-bio], Oxygen, 030220 oncology & carcinogenesis, medicine.symptom, Nuclear localization sequence, Research Article
Abstract: The naked mole rat (NMR), a long-lived and cancer-resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

40. Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment Part A: Early acute phase of sepsis: an extraordinary redox situation (leukocyte-endothelium interaction leading to endothelial damage)

Author: Pierre Van Antwerpen, Xavier Forceville, Jean-Charles Preiser, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier de Meaux, Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Endothelium, endothelium, Physiology, Neutrophils, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Ischemia, free radicals, Cell Communication, medicine.disease_cause, Biochemistry, Microcirculation, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, leukocyte activation, Selenoprotein P, medicine, Leukocytes, Humans, oxidative stress, selenium, Molecular Biology, Cell damage, General Environmental Science, 030102 biochemistry & molecular biology, business.industry, Endothelial Cells, Cell Biology, medicine.disease, 3. Good health, Respiratory burst, 030104 developmental biology, medicine.anatomical_structure, Early Diagnosis, chemistry, redox state, Immunology, General Earth and Planetary Sciences, business, Oxidation-Reduction, Oxidative stress, Peroxynitrite
Abstract: International audience; SIGNIFICANCE: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. CRITICAL ISSUES: Neutrophil production increases dramatically and aggressive, immature forms are released. Leukocyte cross-talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia-reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the endothelial surface layer, reducing flow and damaging the endothelial barrier. Future Direction: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step towards organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.
Published: 2021

41. NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Author: Bernard Robaye, Gilles Kauffenstein, Julie Pelletier, Jean Sévigny, Romuald Brice Babou Kammoe, Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Département de microbiologie-infectiologie et d’immunologie [Québec City, QC, Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Male, Contraction (grammar), Thromboxane, Extracellular nucleotides, lcsh:QR1-502, Biochemistry, lcsh:Microbiology, chemistry.chemical_compound, Mice, 0302 clinical medicine, P2Y 6 receptor, Nucleotide, Receptor, bladder, chemistry.chemical_classification, Contraction, Chemistry, Nucleotides, Hydrolysis, Apyrase, NTPDase1, Smooth muscle contraction, extracellular nucleotides, smooth muscle cells, Smooth muscle cells, Nucleoside triphosphate, Sex, Female, P2Y6 receptor, Muscle Contraction, Bladder, Myocytes, Smooth Muscle, Urinary Bladder, Real-Time Polymerase Chain Reaction, Article, Uridine Diphosphate, 03 medical and health sciences, Antigens, CD, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, sex, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene Expression Profiling, Wild type, contraction, Généralités, Molecular biology, Uridine, 030104 developmental biology, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, 030217 neurology & neurosurgery
Abstract: Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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42. Alzheimer's Disease: Tau Pathology and Dysfunction of Endocytosis

Author: Jean Pierre Brion, Christophe Erneux, Marie-Ange De Fisenne, Marie-Claude Potier, Sarah Houben, Mégane Homa, Kunie Ando, Karelle Leroy, Laboratoire d'histologie générale, de neuroanatomie et de neuropathologie [Bruxelles], Université libre de Bruxelles (ULB), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: 0301 basic medicine, Opinion, Pathology, medicine.medical_specialty, Tau pathology, Amyloid s, Disease, Endocytosis, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, mental disorders, Amyloid precursor protein, Medicine, Dementia, endocytosis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tau, Molecular Biology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, genome-wide association study, biology, business.industry, Médecine pathologie humaine, Neuropathologie, phosphoinositides, Sciences bio-médicales et agricoles, Alzheimer's disease, medicine.disease, amyloid ß, 3. Good health, 030104 developmental biology, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Alzheimer’s disease (AD) is the most common form of dementia. Its prevalence will significantlyincrease in the coming decades, whereas no efficient treatment is currently available. AD hastwo main neuropathological lesions: amyloid plaques and neurofibrillary tangles (NFTs). Amyloidplaques are composed of amyloid ß (Aß) peptides cleaved from the Amyloid Precursor Protein(APP) (Glenner and Wong, 1984). NFTs, present in the brain of AD and related neurodegenerativediseases, are constituted of tau proteins (Brion et al., 1985) in hyperphosphorylated and aggregatedform (Wang and Mandelkow, 2016).
Published: 2021

43. CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Author: Magalie Barth, Marie-Ange Nguyen-Morel, Marie Le Roux, Florence Renaldo, Nathalie Villeneuve, Florence Riant, Alec Aeby, Lionel Arnaud, Arnaud Biraben, Claude Cances, Catheline Vilain, Anne-Isabelle Vermersch, Patrick Van Bogaert, Edouard Hirsch, Chloé Angelini, Laurence Chaton, Gaetan Lesca, Julien Van Gils, Laurent Villard, Sophie Gueden, Patrick Desbordes de Cepoy, Vincent des Portes, Luc Valton, Cecilia Altuzarra, Audrey Riquet, Anne de Saint Martin, Gall, Valérie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Hôpital Erasme [Bruxelles], CHU Strasbourg, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de Bordeaux Pellegrin [Bordeaux], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, medicine.medical_specialty, Early onset absence seizures, Stroke-like, [SDV]Life Sciences [q-bio], Status epilepticus, Lamotrigine, CACNA1A, Absence seizure, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, 030225 pediatrics, medicine, Humans, Spinocerebellar Ataxias, Familial hemiplegic migraine, Drug-resistance, Episodic ataxia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Lennox-gastaut syndrome, General Medicine, medicine.disease, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, Ataxia, Female, Neurology (clinical), Calcium Channels, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lennox–Gastaut syndrome, medicine.drug
Abstract: International audience; CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Published: 2021

44. Radical collaboration during a global health emergency: Development of the RDA COVID-19 data sharing recommendations and guidelines

Author: Amy Pienta, Alejandra Gonzalez-Beltran, Zoe Cournia, Francis P. Crawley, Leyla Jael Castro, Sridhar Gutam, Daniel Mietchen, Timea Biro, Ingvill C. Mochmann, Marcos Roberto Tovani-Palone, Claire C. Austin, Geta Mitrea, Simon Parker, Katherine McNeill, Minglu Wang, Louise Bezuidenhout, Carlos Casorran, Anupama Gururaj, Natalie Harrower, Jitendra Jonnagaddala, Panayiota Polydoratou, Alexander Bernier, Claudia Engelhardt, Kheeran Dharmawardena, Ingrid Dillo, Mary O'Brien-Uhlmansiek, Romain David, Rajini Nagrani, Brian Pickering, Gayo Diallo, University of Oxford, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), European Research Infrastructure on Highly Pathogenic Agents (ERINHA-AISBL), Göttingen State and University Library (SUB Göttingen), Georg-August-University = Georg-August-Universität Göttingen, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Data Archiving and Networked Services (DANS-KNAW), Royal Netherlands Academy of Arts and Sciences (KNAW), and European Project: 824087,EOSC-Life
Subjects: medicine.medical_specialty, Knowledge management, Coronavirus disease 2019 (COVID-19), data sharing, global health, epidemic, pandemic, COVID-19, Research Data Alliance, public health, radical collaboration, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Collective identity, Political science, Global health, medicine, 030304 developmental biology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, business.industry, Public health, 05 social sciences, Articles, General Medicine, 3. Good health, Data sharing, Alliance, Work (electrical), [SHS.GESTION]Humanities and Social Sciences/Business administration, Survey data collection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0509 other social sciences, 050904 information & library sciences, business, Research Article
Abstract: Background: The coronavirus disease 2019 (COVID-19) global pandemic required a rapid and effective response. This included ethical and legally appropriate sharing of data. The European Commission (EC) called upon the Research Data Alliance (RDA) to recruit experts worldwide to quickly develop recommendations and guidelines for COVID-related data sharing. Purpose: The purpose of the present work was to explore how the RDA succeeded in engaging the participation of its community of scientists in a rapid response to the EC request. Methods: A survey questionnaire was developed and distributed among RDA COVID-19 work group members. A mixed-methods approach was used for analysis of the survey data. Results: The three constructs of radical collaboration (inclusiveness, distributed digital practices, productive and sustainable collaboration) were found to be well supported in both the quantitative and qualitative analyses of the survey data. Other social factors, such as motivation and group identity were also found to be important to the success of this extreme collaborative effort. Conclusions: Recommendations and suggestions for future work were formulated for consideration by the RDA to strengthen effective expert collaboration and interdisciplinary efforts.
Published: 2021

45. Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype

Author: Ovidiu Balasel, Pauline Dontaine, Véronique Catros, Martine Dassonville, Julie Soblet, Elisa Kottos, Catheline Vilain, Pascale Perlot, Jonchère, Laurent, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Hearing loss, Spermidine, [SDV]Life Sciences [q-bio], Spermine Synthase, Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, New variant, Enteral administration, 03 medical and health sciences, Epilepsy, Cholestasis, Genetics, medicine, Humans, Exocrine pancreatic insufficiency, Main text, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mendeliome, business.industry, 030305 genetics & heredity, Infant, General Medicine, Failure to thrive, Snyder-Robinson, medicine.disease, 3. Good health, Osteopenia, [SDV] Life Sciences [q-bio], Jejunum, Phenotype, SMS, Child, Preschool, Jejunal Stenosis, Mental Retardation, X-Linked, Spermine, medicine.symptom, business
Abstract: International audience; Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.
Published: 2021

46. Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease

Author: Pierre Lefesvre, Katarina Coolens, Farzad Esni, Nelson Dusetti, Harry Heimberg, Luc Bouwens, Jean-Luc Van Laethem, Yves Heremans, Gunter Leuckx, Patrick Jacquemin, Angel Fernandez Ruiz, Tatjana Arsenijevic, Meritxell Rovira, Christelle Bouchart, Peter In't Veld, Wim Waelput, Ilse Rooman, Sandrina Martens, Nicky D'Haene, Abdessamad El Kaoutari, Jaime Martinez de Villareal, Diedert Luc De Paep, Francisco X. Real, Joan Casamitjana, Hediel Madhloum, Mathias Van Bulck, Vrije Universiteit Brussel (VUB), Université libre de Bruxelles (ULB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Spanish National Cancer Research Center (CNIO), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut Jules Bordet [Bruxelles], Centre de Recherche en Cancérologie de Marseille (CRCM), Basic (bio-) Medical Sciences, Experimental Pathology, Laboratory for Medical and Molecular Oncology, Faculty of Medicine and Pharmacy, Pathology/molecular and cellular medicine, Beta Cell Neogenesis, Cell Differentiation, Surgery, Diabetes Pathology & Therapy, Supporting clinical sciences, Pathology, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UCL - SSS/DDUV - Institut de Duve, and UCL - SSS/DDUV/LPAD - Liver and pancreas differentiation
Subjects: 0301 basic medicine, Pancreatic disease, Cellular differentiation, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, SOX9, Biology, Stem cell marker, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, development genes, stem cells, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Gastro-entérologie, cancer, pancreas, Gastroenterology, imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Stem cell, Pancreas
Abstract: Objective: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas. Design: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed. Results: In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme. Conclusion: In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

47. Maintenance of wakefulness test: how does it predict accident risk in patients with sleep disorders?

Author: Kelly Guichard, Régis Lopez, Jean-Arthur Micoulaud-Franchi, Isabelle Arnulf, Yves Dauvilliers, Mélanie Strauss, Damien Leger, Emilie Pepin, Jacques Taillard, Patricia Sagaspe, Lucie Barateau, Pierre Philip, CCSD, Accord Elsevier, Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Sleep Wake Disorders, medicine.medical_specialty, Automobile Driving, Maintenance of Wakefulness Test, Sleepiness, Accident risk, Disorders of Excessive Somnolence, Near miss, 03 medical and health sciences, 0302 clinical medicine, Sleep disorders, French drivers, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Wakefulness, Sleep disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, MESH: Automobile Driving, business.industry, OSAS, General Medicine, medicine.disease, MESH: Case-Control Studies, MESH: Male, MESH: Sleep Wake Disorders, Test (assessment), Alertness, MESH: Wakefulness, 030228 respiratory system, Case-Control Studies, Physical therapy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep (system call), business, human activities, MESH: Female, 030217 neurology & neurosurgery, MESH: Disorders of Excessive Somnolence, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Narcolepsy
Abstract: International audience; Study objective: To determine whether the objective level of alertness measured by the Maintenance of Wakefulness Test (MWT) is associated with the occurrence of self-reported sleepiness-related traffic near misses and accidents related to sleepiness in patients with sleep disorders.Methods: This case-control study was conducted over a three-year period in four French sleep centers during a 4∗40 min MWT in patients driving more than 5000 Km/year. Relationship between mean sleep latency on the MWT (MWT latency) and age, sex, driving, sleepiness-related near misses and accidents reported during the previous year, and sleep disorder characteristics was analyzed.Results: Of 377 patients suffering from OSAS, idiopathic hypersomnia, narcolepsy, restless leg syndrome or insufficient sleep syndrome, 176 were included. 74 cases reported an accident or near miss related to sleepiness at the wheel in the past year, and 102 reported no accident/near miss (control patients). Thirty-one (37.8 %) cases and 9 (8.8 %) controls reported being sleepy at the wheel more than once a week (p < 0.0001). After adjusted regression analyses, patients with MWT latency between 19 and 33 minutes had a 3.2- (CI 95%[1.5; 6.8], p < 0.0001) fold increase in risk of reporting a near miss/ accident and patients with MWT latency 33 min).Conclusions: MWT latency is associated with self-reported, sleepiness-related near misses and accidents related to sleepiness in the past year in patients routinely investigated in sleep clinics. The MWT could be used to assess driving risk together with clinical interviews assessing sleepiness at the wheel.
Published: 2021

48. Le parcours de soins du patient dans le cadre des CAR T-cell : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Ibrahim Yakoub-Agha, Anne Wallart Brejaud, Isabelle Fournier, Christelle Andrianne, Corinne Courbon, Josiane Delorme, Sarah Bole, Clotilde Aubrun, Maxime Berquier, Damien Lacroix, Ghislaine François, David Beauvais, Marlene Vercasson, Marie-France Jaivenois, Isabelle Mussot, Alexis Caulier, Laetitia Le Bars, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Ambroise Paré [Mons, Belgium], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Amiens-Picardie, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, Care process, Coordinating nurse, [SDV]Life Sciences [q-bio], Hematology, General Medicine, CAR T-cell, 3. Good health, Cell activity, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Nursing, 030220 oncology & carcinogenesis, Political science, Infirmier de coordination, Parcours de soins, Radiology, Nuclear Medicine and imaging
Abstract: International audience; In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.
Published: 2020

49. Mutualisation des outils de qualité pour les cellules CAR-T : recommandations de la Société francophone de greffe de moelle et thérapie cellulaire (SFGM-TC)

Author: Remy Dulery, Jean-Louis Beaumont, Agnes Perrin, Sylvie Carnoy, Cécile Gibault-Joffe, Virginie Ader, Nathalie Contentin, Sophie Plaza-Milhe, Nathalie Fegueux, Philippe Lewalle, Christine Giraud, Marie-Noëlle Lacassagne, Thi Ngoc Phuong Huynh, Alexandre Carpentier, Agnès Bonnin, Marie-Agnès Guerout-Verite, Ibrahim Yakoub-Agha, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-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), Etablissement Français du Sang [Occitanie] (EFS Occitanie), CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire de Genève, Etablissement français du sang [Rennes] (EFS Bretagne), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service Gestion du Risque Infectieux, des Vigilances et Infectiologie (SGRIVI), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service d'hématologie [CRLCC Henri Becquerel], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), CCSD, Accord Elsevier, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Activité électrique du coeur, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, JACIE, Cancer Research, medicine.medical_specialty, CAR T-cells, Lymphoma, [SDV]Life Sciences [q-bio], Cellular therapy, Pharmacy, Acute lymphoblastic leukemia, CAR T-cell, Lymphome, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Therapeutic apheresis, Hematopoietic cell, Quality assessment, business.industry, Leucémie aiguë lymphoblastique, Hematology, General Medicine, Chimeric antigen receptor, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Car t cells, business, Outils de qualité, Thérapie cellulaire
Abstract: International audience; CAR T-cells are anti-cancer immunocellular therapy drugs that involve reprogramming the patient's T-cells using a transgene encoding a chimeric antigen receptor (CAR). Although CAR T-cells are cellular therapies, the organization for manufacturing and delivering these medicinal products is in many ways different from the one for hematopoietic cell grafts or donor lymphocyte infusions. The implementation of this innovative therapy is recent and requires close coordination between clinical teams, the therapeutic apheresis unit, the cell therapy unit, the pharmaceutical laboratory, and pharmacy. Apart from the regulatory texts, which are regularly modified, and the specific requirements of each pharmaceutical laboratory, there is currently no guide to help the centers initiating their activity and there is no specific indicator to assess the quality of the CAR T-cell activity in each center. The purpose of the current harmonization workshop is to clarify the regulatory prerequisites warranted for a center to have a CAR T-cell activity and to propose recommendations for implementing quality tools, in particular indicators, and allowing their sharing.
Published: 2020

50. Real life prospective evaluation of new drug-eluting platform for chemoembolization of patients with hepatocellular carcinoma: Paris registry

Author: Lambros Tselikas, Boris Guiu, Frederic Deschamps, Lucas Raynaud, Thierry de Baere, Marco Dioguardi Burgio, Patrick Chevallier, Maxime Ronot, Gontran Verset, Illario Tancredi, Géraldine Sergent, Université Paris-Saclay, Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: hepatocellular carcinoma, DEM-TACE, doxorubicin, idarubicin, hepatobiliary toxicities, Cancer Research, medicine.medical_specialty, Hepatocellular carcinoma, Hepatobiliary toxicities, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Idarubicin, Progression-free survival, Stage (cooking), Adverse effect, BCLC Stage B Hepatocellular Carcinoma, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sciences bio-médicales et agricoles, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Cancérologie, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, Doxorubicin, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, medicine.drug
Abstract: Background and aim: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearl™, loaded with anthracyclines. Materials and methods: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearl™ loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years. Results: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1–2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)). Conclusions: DEM-TACE using LifePearl™ provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearl™. The trial was registered in ClinicalTrials.gov National Library of Medicine (ID: NCT03053596)., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

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