Author: "Centre Hospitalier Universitaire de Nantes" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Centre Hospitalier Universitaire de Nantes"' showing total 7,170 results

Start Over Author "Centre Hospitalier Universitaire de Nantes"

7,170 results on '"Centre Hospitalier Universitaire de Nantes"'

1. Clinical vAliDation of ARTificial Intelligence in POlyp Detection (CAD-ARTIPOD)

Author: Nuovo Regina Margherita Hospital, Rome, Italy, Krankenhaus Barmherzige Brüder, Regensburg, Germany, Centre Hospitalier Universitaire de Nantes, Nantes, France, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Warschau, Poland, Spire Portsmouth Hospital, Portsmouth, United Kingdom, University Medical Center, Amsterdam, The Netherlands, and University Hospitals Ghent, Ghent, Belgium
Published: 2022

2. A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients

Author: Aurélie Moreau, Delphine Kervella, Laurence Bouchet-Delbos, Cécile Braudeau, Soraya Saïagh, Pierrick Guérif, Sophie Limou, Anne Moreau, Sylvain Bercegeay, Mathias Streitz, Birgit Sawitzki, Ben James, Paul N. Harden, David Game, Qizhi Tang, James F. Markmann, Ian S.D. Roberts, Edward K. Geissler, Brigitte Dréno, Régis Josien, Maria-Cristina Cuturi, Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Christophe Masset, Aurélie Meurette, Simon Ville, Christine Kandell, Karine Renaudin, Florent Delbos, Alexandre Walencik, Anne Devis, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 1 : Mononuclear phagocytes, Immunopathology, Immunovirology (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury (U1064 Inserm - CR2TI), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie et Immunologie Clinique [CHU de Nantes], Unité de Thérapie Cellulaire et Génique [CHU Nantes] (UTCG), Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), UMR 1064 Centre de Recherche en Transplantation et Immunologie, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1064, ITUN - Institut de Transplantation Urologie Nephrologie, Nantes Université - École Centrale de Nantes (Nantes Univ - ECN), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), 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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Friedrich-Loeffler-Institut (FLI), University of Regensburg, Oxford University Hospitals NHS Trust, University of Oxford, Guy's and St Thomas' Hospital [London], University of California [San Francisco] (UC San Francisco), University of California (UC), Massachusetts General Hospital [Boston], University Hospital Regensburg, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Service de dermatologie [Nantes], LabEX IGO Immunothérapie Grand Ouest, DIVAT consortium: Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Delphine Kervella, Christophe Masset, Aurélie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Karine Renaudin, Florent Delbos, Alexandre Walencik, Anne Devis., and KERANDEL-DION, Céline
Subjects: [SDV] Life Sciences [q-bio], tolerance, Nephrology, [SDV]Life Sciences [q-bio], transplantation, clinical trial, dendritic cells, cell therapy
Abstract: International audience; Kidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases. Here, we present the first phase I clinical trial results using human autologous tolerogenic dendritic cells (ATDC) in kidney transplantation. Eight patients received ATDC the day before transplantation in conjunction with standard steroids, mycophenolate mofetil and tacrolimus immunosuppression with an option to taper mycophenolate mofetil. ATDC preparations were manufactured in a Good Manufacturing Practice-compliant facility and fulfilled cell count, viability, purity and identity criteria for release. A control group of nine patients received the same standard immunosuppression, except basiliximab induction replaced ATDC therapy and mycophenolate tapering was not allowed. During the three-year follow-up, no deaths occurred and there was 100% graft survival. No significant increase of adverse events was associated with ATDC infusion. Episodes of rejection were observed in two patients from the ATDC group and one patient from the control group. However, all rejections were successfully treated by glucocorticoids. Mycophenolate was successfully reduced/stopped in five patients from the ATDC group, allowing tacrolimus monotherapy for two of them. Regarding immune monitoring, reduced CD8 T cell activation markers and increased Foxp3 expression were observed in the ATDC group. Thus, our results demonstrate ATDC administration safety in kidney-transplant recipients.
Published: 2023

3. Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods

Author: Y, Zhou, A, Larnaudie, Y, Ghannam, L, Ollivier, Y, Gounane, A, Laville, A, Coutte, A, Huertas, P, Maroun, C, Chargari, S, Bockel, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Département de Radio-Oncologie [Baclesse, Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université d'Angers (UA), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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 de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Groupe Avril, Institut Gustave Roussy (IGR), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and Department of Radiotherapy
Subjects: Antidiabétiques, Lung Neoplasms, Antihypertenseurs, Statin, Antidiabetic treatments, Lipids, Médicaments hypolipémiants, Metformin, Oncology, Lipid-lowering medications, Immunosuppresseurs, Immunosuppressive medications, Humans, Hypoglycemic Agents, Nanoparticles, Radiology, Nuclear Medicine and imaging, Immunotherapy, Antihypertensive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Antihypertensives
Abstract: International audience; The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.
Published: 2022

4. Calcium homeostasis and hyperparathyroidism: Nephrologic and endocrinologic points of view

Author: Lemoine, S., Figueres, L., Bacchetta, J., Frey, S., Dubourg, L., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Filières Maladies Rares ORKID et ERK-Net, Centre de Référence des Maladies Rares du Métabolisme du Phosphore et du Calcium and Filière de Santé Maladies Rares (OSCAR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, and CarMeN, laboratoire
Subjects: Hyperplasia, Calcium sensing receptor, Familial hypocalciuric hypercalcemia, Bone Density Conservation Agents, Hyperparathyroidism, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Hypercalciuria, General Medicine, Hyperparathyroidism, Primary, [SDV] Life Sciences [q-bio], Endocrinology, Calcemia, Parathyroid Hormone, Hypercalcemia, Homeostasis, Humans, Calcium, Receptors, Calcium-Sensing
Abstract: International audience; Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and phosphate excretion, and conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3. Hyperparathyroidism consists in PTH elevation, which may be adapted (secondary hyperparathyroidism) or non-adapted to calcemia levels (primary hyperparathyroidism, familial hypercalcemia/hypocalciuria, tertiary hyperparathyroidism). Primary hyperparathyroidism (PHP) features hypercalcemia and elevated or inappropriate PTH elevation. PHP may be revealed by biological abnormalities such as hypercalcemia and can be accompanied by renal complications (hypercalciuria, nephrolithiasis, nephrocalcinosis) and/or osteoporosis. However, it can also be normocalcemic and calcium loading will be necessary to diagnosis it. The differential diagnosis of PHP is familial hypocalciuric hypercalcemia (FHH), a dominant autosomal disease implicating a calcium sensing receptor-inactivating mutation. It impairs parathyroid cell sensitivity to calcemia elevation and thus induces excessive PTH stimulation, leading to hypercalcemia. Secondary HP (SHP) consists in PTH elevation secondary to a stimulus that needs to be corrected. 25 OHvitD deficiency, kidney failure, renal hypercalciuria, malabsorption and some drugs can induce SHP. Tertiary HP (THP) consists in autonomous PTH secretion by the parathyroid glands after prolonged stimulation under SHP, of whatever cause. This parathyroid autonomy results from the polyclonal hyperplasia observed in SHP progressing toward monoclonal nodular proliferation, leading to nodular hyperplasia or parathyroid adenoma (or, exceptionally, carcinoma), with reduced expression of CaSR and vitamin D receptor. In patients under dialysis, the frontier between SHP and THP is a matter of debate. This review will focus on the pathophysiology of calcium, diagnosis, and management of hyperparathyroidism.
Published: 2022

5. SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents

Author: Barbara B. R. Oliveira-Mendes, Malak Alameh, Béatrice Ollivier, Jérôme Montnach, Nicolas Bidère, Frédérique Souazé, Nicolas Escriou, Flavien Charpentier, Isabelle Baró, Michel De Waard, Gildas Loussouarn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEx Ion Channels Science and Therapeutics [France], Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We thank the Agence Nationale de la Recherche for its financial support to the Région Pays de la Loire (ANR FLASH Covid-19 - CoV2-E-TARGET) and the laboratory of excellence ‘Ion Channels, Science and Therapeutics’ (grant No. ANR-11-LABX-0015)., ANR-20-COVI-0058,CoV2-E-TARGET,Criblage d'inhibiteurs de la protéine E du SARS-CoV-2(2020), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), Loussouarn, Gildas, Criblage d'inhibiteurs de la protéine E du SARS-CoV-2 - - CoV2-E-TARGET2020 - ANR-20-COVI-0058 - COVID-19 - VALID, Laboratoires d'excellence - Canaux ioniques d'intérêt thérapeutique - - ICST2011 - ANR-11-LABX-0015 - LABX - VALID, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), and 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)
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, COVID-19, SARS-CoV-2, viroporins, E protein, 3a protein, pannexin currents, cell death, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, General Medicine
Abstract: Controversial reports have suggested that SARS-CoV E and 3a proteins may be viroporins that conduct currents through the plasma membrane of the infected cells. If true, these proteins would represent accessible targets for the development of new antiviral drugs by using high-throughput patch-clamp techniques. Here we aimed at better characterizing the cell responses induced by E or 3a protein with a particular focus on the ion conductances measured at the cell surface. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly-acquired round shape, tending to detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this hypothesis by using flow cytometry, in agreement with earlier reports on other cell types. In adhering cells expressing E or 3a protein, whole-cell currents were in fact not different from the control condition indicating that E and 3a proteins are not plasma membrane viroporins. In contrast, recording currents on detached cells uncovered outwardly-rectifying currents, much larger than those observed in control. The current characteristics are reminiscent of what was previously observed in cells expressing SARS-CoV-1 E or 3a proteins. Herein, we illustrate for the first time that carbenoxolone blocks these outward currents suggesting that they are conducted by pannexin channels, mostly likely activated by cell morphology change and/or cell death. Alongside we also demonstrate that truncation of the C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent pannexin currents suggesting distinct pathways for cell death and pannexin currents induced by E and 3a proteins. We conclude that SARS-CoV-2 E and 3a proteins are not acting as viroporins expressed at the plasma membrane.Author SummaryA viroporin (or viral porin) is a class of proteins that is encoded by a virus genome. It is named porin because its biological role is to conduct ions through a pore that it created in a lipid membrane such as the one surrounding a human cell. if such viroporin is present at the external membrane of a human cell infected by a virus, it can be an easy target of an antiviral agent which thus does not have to enter the cell to be active. One example of viroporin is the flu M2 protein that is the target of amantadine, an antiviral agent used against flu. In previous studies, two proteins of SARS-CoV viruses, named E protein and 3a protein, have been suggested to be viroporins at the surface of infected human cells, potentially opening a new research avenue against SARS. Here we demonstrate that both proteins are not viroporins at the external membrane but they rather trigger changes in the cell shape and promote cell death. They only indirectly induce the activity of a porin that is encoded by the cell genome, named pannexin.
Published: 2023
Full Text: View/download PDF

6. Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014–2021 French Ouest DataHub

Author: C. Mauguen, A. Maruani, S. Barbarot, C. Abasq, L. Martin, J. Herbert, T. Goronflot, P.-A. Gourraud, A. Happe, A. Descatha, J.-M. Chrétien, A. Beuchée, H. Adamski, A. Dupuy, G. Bouzillé, E. Oger, C. Droitcourt, CHU Pontchaillou [Rennes], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), 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 ), Laboratoire Traitement du Signal et de l'Image (LTSI), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Infantile haemangioma, Post-marketing authorization, Oral propranolol, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Dermatology, Early relapse
Abstract: International audience; BACKGROUND: The factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. OBJECTIVES: To identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. METHODS: We performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. RESULTS: A total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0-78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02-0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. CONCLUSION: The risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.
Published: 2023

7. Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis

Author: Anne-Sophie Boureau, Matilde Karakachoff, Solena Le Scouarnec, Romain Capoulade, Caroline Cueff, Laure de Decker, Thomas Senage, Jean-Philippe Verhoye, Christophe Baufreton, Jean-Christian Roussel, Christian Dina, Vincent Probst, Jean-Jacques Schott, Thierry Le Tourneau, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pontchaillou, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by a PHRC Interregional (API20-20) grant to VP, an ANR & FRM grant [13-BSV6-0011, DCV20070409278] to JJS, by a PHRC Interregional (API12/N/019), a Fédération Française de Cardiologie, a Fondation Coeur et Recherche and an Inserm Translational Research grant to TLT, a 'Connect Talent' research chair from Région Pays de la Loire and Nantes Métropole to RC., ANR-13-BSV6-0011,CavsGen,Variation génétique, transcriptome et épigénome du rétrécissement aortique calcifié(2013), 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), Jonchère, Laurent, and Blanc 2013 - Variation génétique, transcriptome et épigénome du rétrécissement aortique calcifié - - CavsGen2013 - ANR-13-BSV6-0011 - Blanc 2013 - VALID
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Bicuspid aortic valve, Heart Valve Diseases, Calcinosis, Aortic Valve Stenosis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Calcific aortic valve stenosis, Heritability, Bicuspid Aortic Valve Disease, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Aortic Valve, cardiovascular system, Genetics, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine
Abstract: International audience; BACKGROUND: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families. METHODS: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband’s aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV. RESULTS: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h(2) = 0.47, p
Published: 2022

8. Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study

Author: Stephanie Guillet, Etienne Crickx, Imane Azzaoui, pascal chappert, Emmanuelle Boutin, Jean-François Viallard, Etienne Riviere, Delphine Gobert, Lionel Galicier, Marion Malphettes, Stéphane Cheze, Francois Lefrere, Sylvain Audia, Bernard Bonnotte, Olivier Lambotte, Nicolas Noel, Olivier Fain, Guillaume Moulis, Mohamed Hamidou, Mathieu Gerfaud-Valentin, Jean-Pierre Marolleau, Louis Terriou, Nihal Martis, Anne-Sophie Morin, Antoinette Perlat, Thomas Le Gallou, Frédérique Roy-Peaud, Ailsa Robbins, Jean-Christophe Lega, Mathieu Puyade, Thibault Comont, Nicolas Limal, Laetitia Languille, Anissa Zarour, Marine Luka, Mickaël Mathieu Ménager, Thibaut Belmondo, Sophie Hue, Florence Canoui-Poitrine, Marc Michel, Bertrand Godeau, Matthieu Mahevas, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], 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), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Necker - Enfants Malades [AP-HP], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974
Published: 2023

9. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Author: Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio]
Abstract: Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
Published: 2023

10. The radiologically isolated syndrome: revised diagnostic criteria

Author: Lebrun-Frénay, Christine, Okuda, Darin, Siva, Aksel, Landes-Chateau, Cassandre, Azevedo, Christina, Mondot, Lydiane, Carra-Dallière, Clarisse, Zephir, Helene, Louapre, Celine, Durand-Dubief, Françoise, Le Page, Emmanuelle, Bensa, Caroline, Ruet, Aurélie, Ciron, Jonathan, Laplaud, David, Casez, Olivier, Mathey, Guillaume, de Seze, Jerome, Zeydan, Burcu, Makhani, Naila, Tutuncu, Melih, Levraut, Michael, Cohen, Mikael, Thouvenot, Eric, Pelletier, Daniel, Kantarci, Orhun, Sehaki, Sabrina, Devys-Meyer, Nathalie, Bereau, Mathieu, Cappe, Chrystelle, Brochet, Bruno, Ouallet, Jean-Christophe, Kounkou, Katy-Kim, Defer, Gilles, Branger, Pierre, Taithe, Frédéric, Dumont, Emilie, Lescieux, Edwige, Fromont, Agnès, Protin, Alexia, Kane, Maty Diop, Hautecoeur, Patrick, Outteryck, Olivier, Vermersch, Patrick, Boucher, Julie, Petit, Julie, Kasonde, Irène Tabellah, de Vilmarrest, Aymeric, Magy, Laurent, Nicol, Marie, Malbezin, Muriel, Olaiz, Javier, Rigaud-Bully, Claire, Debard, Nadine, Cotton, Sandra Vukusic François, Ionescu, Iuliana, Abdelalli, Amalle, Pelletier, Jean, Audoin, Bertrand, Maarouf, Adil, Di Lelio, Bernadette, Ayrignac, Xavier, Labauge, Pierre, Pinna, Frédéric, Guillemin, Francis, Debouverie, Marc, Ziegler, Amandine, Wiertlevski, Sandrine, Bresch, Saskia, Callier, Céline, David, Elodie, Castelnovo, Giovanni, Papeix, Caroline, Maillart, Elisabeth, Lubetzki, Catherine, Zehrouni, Karima, Fontaine, Bertrand, Giannesini, Claire, Hodel, Jérôme, Wahab, Abir, Zedet, Mickaël, Fagniez, Ombeline, Laage, Clémence, Pottier, Corinne, Slesari, Iuliana, Sampaio, Mathilde, Rabois, Emilie, Castex, Cédric, Hebant, Benjamin, Guillaume, Maxime, Vimont, Christine, Gout, Olivier, Guegen, Antoine, Michel, Laure, Muraz, Romain, Le Port, Damien, Leray, Emmanuelle, Henry, Carole, de Broucker, Thomas, Collongues, Nicolas, Berthe, Carole, Biotti, Damien, Freitas, Noellie, Visneux, Vincent, Forestier, Mélanie, Beltran, Stéphane, Meunier, Géraldine, Servan, Jérôme, Pico, Fernando, Chatagner, Virginie, Radji, Fatai, Morel, Nathalie, Grosset-Jeannin, Deborah, Ungureanu, Aurelian, Boyer, Latine, Suchet, Laurent, Lebrun-Frenay, Christine, Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), University of Texas Southwestern Medical Center [Dallas], Cerrahpasa Faculty of Medicine, Istanbul University, University of Southern California (USC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Translational Research in Autoimmunity and Inflammation Group (TIMC-T-RAIG), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CHU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Mayo Clinic [Rochester], Yale School of Medicine [New Haven, Connecticut] (YSM), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and None
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience, diagnostic criteria, radiologically isolated syndrome, Neurology (clinical), prognosis, multiple sclerosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MRI
Abstract: The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1–2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.
Published: 2023

11. Invasive bone and joint infections from the French Scedosporiosis/lomentosporiosis Observational Study (SOS) cohort: no mortality with long-term antifungal treatment and surgery

Author: Damien Blez, Didier Bronnimann, Blandine Rammaert, Valérie Zeller, Laurence Delhaes, Laurent Hustache, Frédéric Grenouillet, Nicolas Traversier, Julie Bonhomme, Taieb Chouaki, Thomas Perpoint, Florence Persat, Marie Elisabeth Bougnoux, Sophie Bayle, Luc Quaesaet, Gilles Nevez, David Boutoille, Florent Morio, Laurence Pougnet, Viviane Queyrel-Moranne, B́eate Heym, Romain Guillemain, Éric Dannaoui, Antoine Roux, Dea Garcia-Hermoso, Fanny Lanternier, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier Diaconesses Croix Saint-Simon, INSERM U1045, IHU-LIRYC, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (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 Félix-Guyon [Saint-Denis, La Réunion], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital d'Instruction des Armées 'Clermont-Tonnerre' (HIA), Hôpital Pasteur [Nice] (CHU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Hôpital Foch [Suresnes]
Subjects: Infectious Diseases, arthritis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, osteomyelitis, Lomentospora, bone infections, Scedosporium, General Medicine, scedosporiosis
Abstract: Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.
Published: 2023

12. The mechanosensitive <scp>TRPV2</scp> calcium channel promotes human melanoma invasiveness and metastatic potential

Author: Kenji F Shoji, Elsa Bayet, Sabrina Leverrier‐Penna, Dahiana Le Devedec, Aude Mallavialle, Séverine Marionneau‐Lambot, Florian Rambow, Raul Perret, Aurélie Joussaume, Roselyne Viel, Alain Fautrel, Amir Khammari, Bruno Constantin, Sophie Tartare‐Deckert, Aubin Penna, Pecqueret, Valérie, 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 ), Canaux et Connexines dans les Cancers et Cellules Souches (4CS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire], Universität Duisburg-Essen [Essen], West German Cancer Center [Essen, Germany], 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), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR‐12‐JSV2‐0004‐001, Agence Nationale de la Recherche, PJA20151203419, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Université de Rennes 1, and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: [SDV] Life Sciences [q-bio], migration, [SDV]Life Sciences [q-bio], Medizin, melanoma, Genetics, metastasis, calpain, Molecular Biology, Biochemistry, TRPV2 channel
Abstract: Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing, which is fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination of melanoma cells during metastasis, is therefore of primary importance. Here, we uncover the prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic dissemination. In vitro as well as in vivo, TRPV2 activity is sufficient to confer both migratory and invasive potentials, while conversely TRPV2 silencing in highly metastatic melanoma cells prevents aggressive behavior. In invasive melanoma cells, TRPV2 channel localizes at the leading edge, in dynamic nascent adhesions, and regulates calcium-mediated activation of calpain and the ensuing cleavage of the adhesive protein talin, along with F-actin organization. In human melanoma tissues, TRPV2 overexpression correlates with advanced malignancy and poor prognosis, evoking a biomarker potential. Hence, by regulating adhesion and motility, the mechanosensitive TRPV2 channel controls melanoma cell invasiveness, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma. ispartof: EMBO REPORTS vol:24 issue:4 ispartof: location:England status: published
Published: 2023

13. Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis

Author: Emmanuelle Godefroy, Laure Barbé, Béatrice Le Moullac-Vaidye, Jézabel Rocher, Adrien Breiman, Sébastien Leuillet, Denis Mariat, Jean-Marc Chatel, Nathalie Ruvoën-Clouet, Thomas Carton, Francine Jotereau, Jacques Le Pendu, Nantes Université (Nantes Univ), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Biofortis Mérieux NutriSciences [Saint-Herblain], 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), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Pecqueret, Valérie
Subjects: Microbiology (medical), [SDV] Life Sciences [q-bio], rotavirus, Faecalibacterium prausnitzii, FUT2, [SDV]Life Sciences [q-bio], fucosylation, antibodies, Inflammatory diseases, Microbiology, histo-blood group antigens, regulatory T cells
Abstract: The FUT2 α1,2fucosyltransferase contributes to the synthesis of fucosylated glycans used as attachment factors by several pathogens, including noroviruses and rotaviruses, that can induce life-threatening gastroenteritis in young children. FUT2 genetic polymorphisms impairing fucosylation are strongly associated with resistance to dominant strains of both noroviruses and rotaviruses. Interestingly, the wild-type allele associated with viral gastroenteritis susceptibility inversely appears to be protective against several inflammatory or autoimmune diseases for yet unclear reasons, although a FUT2 influence on microbiota composition has been observed. Here, we studied a cohort of young healthy adults and showed that the wild-type FUT2 allele was associated with the presence of anti-RVA antibodies, either neutralizing antibodies or serum IgA, confirming its association with the risk of RVA gastroenteritis. Strikingly, it was also associated with the frequency of gut microbiota-induced regulatory T cells (Tregs), so-called DP8α Tregs, albeit only in individuals who had anti-RVA neutralizing antibodies or high titers of anti-RVA IgAs. DP8α Tregs specifically recognize the human symbiont Faecalibacterium prausnitzii, which strongly supports their induction by this anti-inflammatory bacterium. The proportion of F. prausnitzii in feces was also associated with the FUT2 wild-type allele. These observations link the FUT2 genotype with the risk of RVA gastroenteritis, the microbiota and microbiota-induced DP8α Treg cells, suggesting that the anti-RVA immune response might involve an induction/expansion of these T lymphocytes later providing a balanced immunological state that confers protection against inflammatory diseases.
Published: 2023

14. Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self

Author: Katherine Walwyn-Brown, Jason Pugh, Alexander T.H. Cocker, Niassan Beyzaie, Bernhard B. Singer, Daniel Olive, Lisbeth A. Guethlein, Peter Parham, Zakia Djaoud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), Department of Structural Biology [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford University, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), and EFS Centre-Pays de la Loire [Nantes]
Subjects: Cancer Research, Butyrophilins, [SDV]Life Sciences [q-bio], Immunology, Receptors, Antigen, T-Cell, gamma-delta, Article, Killer Cells, Natural, Antigens, CD, Neoplasms, Cytokines, Humans, Immunotherapy, Intraepithelial Lymphocytes, T-Lymphocytes, Cytotoxic
Abstract: γδ T cells stimulated by phosphoantigens (pAg) are potent effectors that secrete Th1 cytokines and kill tumor cells. Consequently, they are considered candidates for use in cancer immunotherapy. However, they have proven only moderately effective in several clinical trials. We studied the consequences of pAg-stimulated γδ T-cell interactions with natural killer (NK) cells and CD8+ T cells, major innate and adaptive effectors, respectively. We found that pAg-stimulated γδ T cells suppressed NK-cell responses to “missing-self” but had no effect on antigen-specific CD8+ T-cell responses. Extensive analysis of the secreted cytokines showed that pAg-stimulated γδ T cells had a proinflammatory profile. CMV-pp65–specific CD8+ T cells primed with pAg-stimulated γδ T cells showed little effect on responses to pp65-loaded target cells. By contrast, NK cells primed similarly with γδ T cells had impaired capacity to degranulate and produce IFNγ in response to HLA class I–deficient targets. This effect depended on BTN3A1 and required direct contact between NK cells and γδ T cells. γδ T-cell priming of NK cells also led to a downregulation of NKG2D and NKp44 on NK cells. Every NK-cell subset was affected by γδ T cell–mediated immunosuppression, but the strongest effect was on KIR+NKG2A– NK cells. We therefore report a previously unknown function for γδ T cells, as brakes of NK-cell responses to “missing-self.” This provides a new perspective for optimizing the use of γδ T cells in cancer immunotherapy and for assessing their role in immune responses to pAg-producing pathogens.See related Spotlight by Kabelitz, p. 543.
Published: 2022

15. Applications of artificial intelligence and machine learning for the hip and knee surgeon: current state and implications for the future

Author: Christophe Nich, Julien Behr, Vincent Crenn, Nicolas Normand, Harold Mouchère, Gaspard d’Assignies, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Orthopédie [CCOT, CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Clinique Chirurgicale Orthopédique et Traumatologique - CCOT [CHU Nantes], Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Image Perception Interaction (LS2N - équipe IPI), Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Centre Hospitalier Départemental site de la Roche-sur-Yon (CHD de la Roche-sur-Yon), and Incepto Medical
Subjects: Machine Learning, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Knee Joint, Lower Extremity, Artificial Intelligence, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Humans, Orthopedics and Sports Medicine, Surgery, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], ComputingMilieux_MISCELLANEOUS, Forecasting
Abstract: Artificial Intelligence (AI)/Machine Learning (ML) applications have been proven efficient to improve diagnosis, to stratify risk, and to predict outcomes in many respective medical specialties, including in orthopaedics.Regarding hip and knee reconstruction surgery, AI/ML have not made it yet to clinical practice. In this review, we present sound AI/ML applications in the field of hip and knee degenerative disease and reconstruction. From osteoarthritis (OA) diagnosis and prediction of its advancement, clinical decision-making, identification of hip and knee implants to prediction of clinical outcome and complications following a reconstruction procedure of these joints, we report how AI/ML systems could facilitate data-driven personalized care for our patients.
Published: 2022

16. Frequency and Genomic Aspects of Intrinsic Resistance to Vismodegib in Locally Advanced Basal Cell Carcinoma

Author: Andrey A. Yurchenko, Oltin T. Pop, Meriem Ighilahriz, Ismael Padioleau, Fatemeh Rajabi, Hayley J. Sharpe, Nicolas Poulalhon, Brigitte Dreno, Amir Khammari, Marc Delord, Antonio Alberti, Nadem Soufir, Maxime Battistella, Samia Mourah, Fanny Bouquet, Ariel Savina, Andrej Besse, Max Mendez-Lopez, Florent Grange, Sandrine Monestier, Laurent Mortier, Nicolas Meyer, Caroline Dutriaux, Caroline Robert, Philippe Saiag, Florian Herms, Jerome Lambert, Frederic J. de Sauvage, Nicolas Dumaz, Lukas Flatz, Nicole Basset-Seguin, Sergey I. Nikolaev, Pecqueret, Valérie, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Brustzentrum Kantonsspital St. Gallen, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The Babraham Institute [Cambridge, UK], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre 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), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut ROCHE [Boulogne-Billancourt], Roche S.A.S, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital de la Timone [CHU - APHM] (TIMONE), Equipe 3 - Facteurs de persistance des cellules leucémique - (INSERM U837), Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Ambroise Paré [AP-HP], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Genentech, Inc., and Genentech, Inc. [San Francisco]
Subjects: Cancer Research, Skin Neoplasms, animal structures, integumentary system, Pyridines, [SDV]Life Sciences [q-bio], fungi, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Carcinoma, Basal Cell, Humans, Anilides, Hedgehog Proteins, Cerebellar Neoplasms
Abstract: Purpose: Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms. Experimental Design: Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC). Results: We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate. Conclusions: IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.
Published: 2022

17. Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways

Author: Marine Charrier, Judith Lorant, Rafael Contreras-Lopez, Gautier Téjédor, Christophe Blanquart, Blandine Lieubeau, Cindy Schleder, Isabelle Leroux, Sophie Deshayes, Jean-François Fonteneau, Candice Babarit, Antoine Hamel, Armelle Magot, Yann Péréon, Sabrina Viau, Bruno Delorme, Patricia Luz-Crawford, Guillaume Lamirault, Farida Djouad, Karl Rouger, École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), 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), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidad de los Andes [Santiago] (UANDES), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Macopharma [Mouvaux], and Bernardo, Elizabeth
Subjects: Medicine (General), Research, Medicine (miscellaneous), Mesenchymal Stem Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, QD415-436, Lymphocyte Activation, Muscular dystrophy, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Coculture Techniques, Cell therapy, Immunomodulation, Adult Stem Cells, R5-920, [SDV.CAN] Life Sciences [q-bio]/Cancer, T-cell, Human adult stem cell, Molecular Medicine, Humans, MuStem cell, Cell Proliferation
Abstract: Background Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling. Methods The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity. Results Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one. Conclusions Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.
Published: 2022

18. Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature

Author: Bastien Jamet, Axel Cailleteau, Cyrille Touzeau, Stéphane Supiot, Valentine Guimas, Emmanuel Jouglar, Bernardo, Elizabeth, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Site de Recherche Intégrée sur le Cancer - SIRIC « ILIAD » [Nantes], and Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9)
Subjects: medicine.medical_specialty, medicine.medical_treatment, R895-920, [SDV.CAN]Life Sciences [q-bio]/Cancer, Case Report, Radiation oncology, Gastroenterology, Medical physics. Medical radiology. Nuclear medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cytokine release syndrome, Multiple myeloma, Total body irradiation, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Respiratory system, Tumor lysis syndrome, RC254-282, Leukemia, Hematology, Radiotherapy, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Radiation therapy, Oncology, business
Abstract: Highlights • Radiotherapy can trigger cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs. • Extreme caution must be given when irradiating large tumor volumes at high risk of tumor lysis. • Evidence of cytokine release following radiotherapy unveils the systemic interactions of radiotherapy with the immune system., We present the case of a 53-year-old woman treated with analgesic radiotherapy for a multiple myeloma bone lesion of the forearm. After a first fraction of 5 Gray (Gy), she presented with an acute respiratory syndrome with fever a few hours after the treatment. The same symptoms occurred after the second fraction 3 days later. The patient recovered quickly thanks to intravenous hydration and suspension of the radiotherapy. Biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. This is the second time in the literature that cytokine release syndrome has been described following radiotherapy. First, we synthesize TLS and radiotherapy to determine how radiotherapy could be a trigger associated with other well-known factors. Furthermore, we discuss radiotherapy and cytokine release syndrome. Summary We present the case of a woman treated with analgesic radiotherapy for a multiple myeloma bone lesion. Following the first and the second treatment fraction, the patient presented with an acute respiratory syndrome with fever and biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. Furthermore, we discuss how radiotherapy could be a trigger of cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs.
Published: 2022

19. Comparative assessment of complete-coverage, fixed tooth-supported prostheses fabricated from digital scans or conventional impressions: A systematic review and meta-analysis

Author: Alexis Gaudin, Elhadj Babacar Mbodj, Octave Nadile Bandiaky, Jean-Benoit Hardouin, Marjorie Cheraud-Carpentier, Assem Soueidan, Pierre Le Bars, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Université de Nantes - UFR Odontologie, Université de Nantes (UN), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Unité d'investigation clinique Odontologie [CHU Nantes] (UIC11), Centre hospitalier universitaire de Nantes (CHU Nantes), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Jehan, Frederic, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)
Subjects: [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Dental Impression Technique, Databases, Factual, Visual analog scale score, Computer science, Population, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, 10. No inequality, education, Patient comfort, Orthodontics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, education.field_of_study, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Dental Impression Materials, 030206 dentistry, Dental Marginal Adaptation, Impression, Clinical trial, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Dental Prosthesis Design, Meta-analysis, Computer-Aided Design, Oral Surgery
Abstract: International audience; Statement of problem: Intraoral scanners have significantly improved over the last decade. Nevertheless, data comparing intraoral digital scans with conventional impressions are sparse.Purpose: The purpose of this systematic review and meta-analysis was to determine the impact of impression technique (digital scans versus conventional impressions) on the clinical time, patient comfort, and marginal fit of tooth-supported prostheses.Material and methods: The authors conducted a literature search based on the Population, Intervention, Comparison, and Outcome (PICO) framework in 3 databases to identify clinical trials with no language or date restrictions. The mean clinical time, patient comfort, and marginal fit values of each study were independently extracted by 2 review authors and categorized according to the scanning or impression method. The authors assessed the study-level risk of bias.Results: A total of 16 clinical studies met the inclusion criteria. The mean clinical time was statistically similar for digital scan procedures (784 ±252 seconds) and for conventional impression methods (1125 ±159 seconds) (P>.05). The digital scan techniques were more comfortable for patients than conventional impressions; the mean visual analog scale score was 67.8 ±21.7 for digital scans and 39.6 ±9.3 for conventional impressions (P.05).Conclusions: Digital scan techniques are comparable with conventional impressions in terms of clinical time and marginal fit but are more comfortable for patients than conventional impression techniques.
Published: 2022

20. Eco-friendly processes for the synthesis of amorphous calcium carbonate nanoparticles in ethanol and their stabilisation in aqueous media

Author: Lauriane Chuzeville, Frank Boury, David Duday, Resmi Anand, Enzo Moretto, Jean-Sébastien Thomann, Luxembourg Institute of Science and Technology (LIST), University of Luxembourg [Luxembourg], Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), and Bernardo, Elizabeth
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, Environmental Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pollution
Abstract: International audience; Amorphous calcium carbonate nanoparticles (ACC NPs) are promising multifunctional materials for healthcare applications. Due to their instability in aqueous media, pure ACC NPs for the biomedical field are increasingly synthesised in absolute ethanol, using the ammonia diffusion method (ADM). Although this method presents the advantage of providing stable ACC NPs without additives, it requires the use of pure ethanol as solvent. New insights into the formation mechanisms of ACC NPs in ethanol using gas diffusion are presented in this article. The optimisation of the process according to these findings can increase the mass concentration of ACC NPs by a factor of 3.5. As a result, the amount of ethanol required to produce a target mass of particles is significantly decreased, reducing the ecological impact of the process. The stabilisation of the resulting ACC NPs in aqueous media is achieved by a short-time process using phospholipids based on the ethanol injection method. By using the natural electrostatic affinity of negatively charged materials for the positive surface of ACC NPs in ethanol, we reduced the process time from 24 h to 2 minutes, compared with the closest state of the art, decreasing the operating time and corresponding energy consumption. The process does not require the use of synthetic PEGylated lipids for steric stabilisation. In addition, a natural egg-sourced phospholipid was identified as an efficient stabiliser for the first time. The upscaling of our process was successfully demonstrated using a 50 L reactor for bulk synthesis, as well as a continuous flow reactor for industrial continuous flow production.
Published: 2022

21. Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases

Author: Lionel Fizanne, Alexandre Villard, Nadia Benabbou, Sylvain Recoquillon, Raffaella Soleti, Erwan Delage, Mireille Wertheimer, Xavier Vidal‐Gómez, Thibauld Oullier, Samuel Chaffron, M. Carmen Martínez, Michel Neunlist, Jérôme Boursier, Ramaroson Andriantsitohaina, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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 Bretagne Loire (UBL), Institut des Maladies de l'Appareil Digestif, and Université de Nantes (UN)
Subjects: Histology, gut microbiota, intestinal permeability, [SDV]Life Sciences [q-bio], non-alcoholic fatty liver disease, Cell Biology, extracellular vesicles
Abstract: International audience; The role of extracellular vesicles (EVs) from faeces (fEVs) and small circulating EVs (cEVs) in liver diseases such as non-alcoholic fatty diseases (NAFLD) and nonalcoholic steatohepatitis (NASH) has not been demonstrated. fEVs and cEVs of healthy donors, NAFLD and NASH patients were isolated and characterized. The effects of EVs were evaluated in intestinal, endothelial, Kupffer and stellate cells. Nonmuscular myosin light chain kinase (nmMLCK) deficient mice were used in vivo. Bacterial origins of fEVs were analysed by 16s rDNA gene sequencing. fEVs and small cEVs were composed of prokaryotic and eukaryotic origins. Only NASH-fEVs exerted deleterious effects. NASH-fEVs increased intestinal permeability and reduced expression of tight junction proteins that were prevented by nmMLCK inhibition, increased endothelial cell permeability and inflammatory cytokines and chemokines requiring TLR4/lipopolysaccharide pathway. NASH-fEVs and NASH-cEVs activated profibrotic and proinflammatory proteins of hepatic stellate cells. Treatment with NASH-fEVs evoked an increase in intestinal permeability in wild type but not in nmMLCK deficient mice. Bacterial origins of fEVs were different between NAFLD and NASH patients and 16 amplicon sequence variants were differentially abundant. We demonstrate that fEVs actively participate in barrier dysfunctions leading to liver injuries underscoring the role of nmMLCK and lipopolysaccharide carried by fEVs.
Published: 2023

22. Striking differences in weight gain after cART initiation depending on early or advanced presentation: Results from the ANRS CO4 FHDH cohort

Author: Sophie Grabar, Valérie Potard, Lionel Piroth, Sophie Abgrall, Louis Bernard, Clotilde Allavena, Fabienne Caby, Pierre de Truchis, Claudine Duvivier, Patricia Enel, Christine Katlama, Marie-Aude Khuong, Odile Launay, Sophie Matheron, Giovanna Melica, Hugues Melliez, Jean-Luc Meynard, Juliette Pavie, Laurence Slama, Sylvie Bregigeon, Pierre Tattevin, Jacqueline Capeau, Dominique Costagliola, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Victor Dupouy, Hôpital Raymond Poincaré [Garches], Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), CHU Pitié-Salpêtrière [AP-HP], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Cochin [AP-HP], CIC Cochin Pasteur (CIC 1417), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Henri Mondor, Hôpital de Riaumont [Lievin], Hôpital Hôtel-Dieu [Paris], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], The ANRS CO4 FHDH is supported by the ANRS-MIE (Agence Nationale de Recherche sur le Sida et les hépatites virales-Maladies Infectieuse Emergentes), INSERM (Institut National de la Santé et de la Recherche Médicale) and the French Ministry of Health. The funders had no role in the study design, data collection, data analysis and interpretation, or writing of the report., 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), Institut Pasteur [Paris] (IP), CHU Henri Mondor, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and GRABAR, SOPHIE
Subjects: Pharmacology, Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology (medical)
Abstract: BackgroundMany studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018.MethodsFrom the French Hospital Database HIV cohort, we assessed factors associated with a weight gain ≥10%, weight change after cART initiation or BMI increase ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load ResultsAt 30 months, 34.5% (95% CI: 33.5–35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6–22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9–65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0–3.7) for those with early presentation and 9.7 kg (95% CI: 8.4–11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir.ConclusionsAfter initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.
Published: 2023

23. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues—Recommendations from the European LeukemiaNet

Author: Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Béné, Peter Valent, Jeroen te Marvelde, Orianne Wagner‐Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink‐Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subirá, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiß, Wolfgang Kern, Arjan van de Loosdrecht, Hematology laboratory, Internal medicine, Hematology, VU University medical center, AII - Cancer immunology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radboudumc Nijmegen [The Netherlands], University Hospitals Bristol, Amsterdam UMC - Amsterdam University Medical Center, Royal Marsden Hospital [Surrey, UK], Lund University [Lund], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Medizinische Universität Wien = Medical University of Vienna, 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), CHU Henri Mondor, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Karolinska Institutet [Stockholm], King‘s College London, Maastricht University [Maastricht], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad de Salamanca, Instituto de Salud Carlos III [Madrid] (ISC), Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), Evangelismos Athens General Hospital, Universidad de Guadalajara, Humanitas University [Milan] (Hunimed), University of Melbourne, Munich Leukemia Laboratory [Munich, Germany], MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Immunology, and Bernardo, Elizabeth
Subjects: Histology, MASTOCYTOSIS, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], BONE-MARROW, DIAGNOSTIC-CRITERIA, [SDV.CAN]Life Sciences [q-bio]/Cancer, REFRACTORY CYTOPENIA, CLASSIFICATION, Pathology and Forensic Medicine, pre-analytic issues, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, MDS, 030304 developmental biology, 0303 health sciences, flow cytometry, Cell Biology, QUANTIFICATION, LOW-GRADE, 3. Good health, CONSENSUS STATEMENTS, ELN, 030215 immunology, STANDARDS
Abstract: Contains fulltext : 290818.pdf (Publisher’s version ) (Open Access) BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice. 01 januari 2023
Published: 2023

24. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author: Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Dartigeas, Caroline, Schneider, Christof, Mottok, Anja, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Tournilhac, Olivier, Bernhart, Stephan H., Chteinberg, Emil, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Ammerpohl, Ole, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, Stilgenbauer, Stephan, Publica, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Biologique [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), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Service d'hématologie [Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institute of pathology [Würzburg], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Epigenomics, Chronic lymphocytic leukaemia, Lymphoma, B-Cell, B-Zell-Lymphom, biostatistics, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Biochemistry, Genetics and Molecular Biology, integrative genomics, DDC 570 / Life sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:570, ddc:610, Transcriptomics, Epigenetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, B-cell lymphoma, Gene Expression Profiling, Computational Biology, classifiers, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computational biology and bioinformatics, DLBCL, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic lymphocytic leukemia, Epigenetics, Richter syndrome, DDC 610 / Medicine & health, CLL
Abstract: Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis., publishedVersion
Published: 2023

25. Mortality in hepatitis C virus-cured vs. hepatitis C virus-uninfected people with HIV: a matched analysis in the ANRS CO4 FHDH cohort

Author: Requena, Maria-Bernarda, Grabar, Sophie, Lanoy, Emilie, Pialoux, Gilles, Billaud, Eric, Duvivier, Claudine, Merle, Philippe, Piroth, Lionel, Tattevin, Pierre, Salmon, Dominique, Weiss, Laurence, Costagliola, Dominique, Lacombe, Karine, Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 ), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Sidaction
Subjects: direct-acting antiviral agents, HIV/Hepatitis C coinfection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, sustained virologic response, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, mortality
Abstract: International audience; Objective: It is unknown whether HCV-cured people with HIV (PWH) without cirrhosis reached the same mortality risk as HCV-uninfected PWH. We aimed to compare mortality in PWH cured of HCV by direct-acting antivirals (DAAs) to mortality in individuals with HIV monoinfection. Design: Nationwide hospital cohort. Methods: HIV-controlled participants without cirrhosis and HCV-cured by DAAs started between 09/2013 and 09/2020, were matched on age (±5 years), sex, HIV transmission group, AIDS status, and BMI (±1 kg/m 2) to up to ten participants with a virally suppressed HIV monoinfection followed at the time of HCV cure ± 6 months. Poisson regression models with robust variance estimates were used to compare mortality in both groups after adjusting for confounders. Results: The analysis included 3961 HCV-cured PWH (G1) and 33 872 HCV-uninfected PWH (G2). Median follow-up was 3.7 years in G1 (interquartile range (IQR): 2.0-4.6), and 3.3 years in G2. Median age was 52.0 years (IQR: 47.0–56.0), and 29 116 (77.0%) were men. There were 150 deaths in G1 (adjusted incidence rate (aIR): 12.2/1000 person-years) and 509 (aIR: 6.3/1000 person-years) in G2, with an incidence rate ratio (IRR): 1.9 [95%CI, 1.4–2.7]. The risk remained elevated 12 months post HCV cure (IRR: 2.4 [95%CI, 1.6–3.5]). Non-AIDS/nonliver-related malignancy was the most common cause of death in G1 (28 deaths).Conclusions: Despite HCV cure and HIV viral suppression, after controlling on factors related to mortality, DAA-cured PWH without cirrhosis remain at higher risk of all-cause mortality than people with HIV monoinfection. A better understanding of the determinants of mortality is needed in this population.
Published: 2023

26. Effects of socioeconomic status on excess mortality in patients with multiple sclerosis in France: A retrospective observational cohort study

Author: Sarah Wilson, Floriane Calocer, Fabien Rollot, Mathieu Fauvernier, Laurent Remontet, Laure Tron, Sandra Vukusic, Emmanuelle Le Page, Marc Debouverie, Jonathan Ciron, Aurélie Ruet, Jérôme De Sèze, Hélène Zephir, Thibault Moreau, Christine Lebrun-Frénay, David-Axel Laplaud, Pierre Clavelou, Pierre Labauge, Eric Berger, Jean Pelletier, Olivier Heinzlef, Eric Thouvenot, Jean Philippe Camdessanché, Emmanuelle Leray, Olivier Dejardin, Gilles Defer, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Fondation Eugène Devic EDMUS, Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bordeaux (UB), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Lille, Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Lille] (CRC-SEP Nord-Pas de Calais), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre 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), Université de Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHI Poissy-Saint-Germain, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), EHESP-ARENES (EHESP-ARENES), École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Service de neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and EHESP, SCD
Subjects: Multiple sclerosis, Flexible model, Net survival, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Health Policy, Socio-economic status, Internal Medicine, Observational cohort study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Excess mortality
Abstract: International audience; Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status.Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality.Findings: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = -6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%-22.9%]) for men and 12.3% (95%CI [7.6%-17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients.Interpretation: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality.
Published: 2023

27. Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales

Author: Agnès B. Jousset, Sandrine Bernabeu, Cécile Emeraud, Rémy A. Bonnin, Alexandra Lomont, Jean Ralph Zahar, Audrey Merens, Christophe Isnard, Nathalie Soismier, Eric Farfour, Vincent Fihman, Nicolas Yin, Olivier Barraud, Hervé Jacquier, Anne-Gaëlle Ranc, Frédéric Laurent, Stéphane Corvec, Louise Ruffier d'Epenoux, Emmanuelle Bille, Nicolas Degand, Chloé Plouzeau, Thomas Guillard, Vincent Cattoir, Asaf Mizrahi, Antoine Grillon, Frédéric Janvier, Cécile Le Brun, Marlène Amara, Mathilda Bastide, Alban Lemonnier, Laurent Dortet, Centre National de Référence Associé de la Résistance aux Antibiotiques [Hôpital Bicêtre AP-HP] (CNRARA/Service de Microbiologie), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Microbiologie [Hôpital Bicêtre AP-HP] (UBH : Unité de Bactériologie-Hygiène), Service de bactériologie-Virologie-Hygiène [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Hôpital Foch [Suresnes], CHU Henri Mondor, Institut Gustave Roussy (IGR), CHU Limoges, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Bactériologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Archet 2 [Nice] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Bactériologie et Hygiène Hospitalière [Rennes], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 ), Groupe Hospitalier Paris Saint-Joseph (hpsj), 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), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Plateau technique de microbiologie, Laboratoire de bactériologie, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Biologie [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), This work was partially supported by MSD and bioMérieux., Pecqueret, Valérie, and CHU Henri Mondor [Créteil]
Subjects: Microbiology (medical), MESH: Escherichia coli, Ceftolozane-tazobactam, [SDV]Life Sciences [q-bio], Immunology, MESH: Tazobactam, MESH: Pseudomonas Infections, MESH: beta-Lactamases, Microbiology, MESH: Prospective Studies, [SDV] Life Sciences [q-bio], MESH: Enterobacteriaceae, carbapenemase, MESH: Cephalosporins, Enterobacterales, ESBL, MESH: Anti-Bacterial Agents, MESH: Pseudomonas aeruginosa, Immunology and Allergy, epidemiology, France, MIC
Abstract: International audience; Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020.Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD.
Published: 2023

28. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group

Author: Loosdrecht, Arjan, Kern, Wolfgang, Porwit, Anna, Valent, Peter, Kordasti, Sharham, Cremers, Eline, Alhan, Canan, Duetz, Carolien, Dunlop, Alan, Hobo, Willemijn, Preijers, Frank, Wagner‐ballon, Orianne, Chapuis, Nicolas, Fontenay, Michaela, Bettelheim, Peter, Eidenschink‐brodersen, Lisa, Font, Patricia, Johansson, Ulrika, Loken, Michael, Marvelde, Jeroen, Matarraz, Sergio, Ogata, Kiyoyuki, Oelschlaegel, Uta, Orfao, Alberto, Psarra, Katherina, Subirá, Dolores, Wells, Denise, Béné, Marie, Della Porta, Matteo, Burbury, Kate, Bellos, Frauke, Velden, Vincent, Westers, Theresia, Saft, Leonie, Ireland, Robin, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Amsterdam UMC - Amsterdam University Medical Center, Munich Leukemia Laboratory [Munich, Germany] (M2L), Lund University [Lund], Medizinische Universität Wien = Medical University of Vienna, King‘s College London, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], The Royal Marsden, Radboud University Medical Center [Nijmegen], Hôpital Henri Mondor, 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], University Hospitals Bristol, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Salamanca, Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Evangelismos Athens General Hospital, Universidad de Guadalajara, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Humanitas University [Milan] (Hunimed), Istituto Clinico Humanitas [Milan] (IRCCS Milan), University of Melbourne, Karolinska Institutet [Stockholm], King's College Hospital (KCH), Hematology, CCA - Cancer biology and immunology, Internal medicine, Hematology laboratory, Immunology, and Bernardo, Elizabeth
Subjects: standardization, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], flow cytometry, CONSORTIUM, [SDV.CAN]Life Sciences [q-bio]/Cancer, PROGNOSTIC SCORING SYSTEM, DIAGNOSIS, CYTOGENETICS, myelodysplastic syndromes, CLASSIFICATION, VALIDATION, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, consensus, hemic and lymphatic diseases, CELLS, SUBGROUPS, ELN, CYTOMORPHOLOGY
Abstract: Contains fulltext : 290800.pdf (Publisher’s version ) (Open Access) This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients. 01 januari 2023
Published: 2023

29. Analysis of elite road‐cycling sprints in relation to maximal power‐velocity‐endurance profile: a longitudinal one‐case study

Author: Sylvain Dorel, Maxime Robin, Antoine Nordez, Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Le Mans Université (UM), Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), French Institute of Sport (INSEP), Research Department, Laboratory Sport, Expertise and Performance (EA7370) (SEP (EA7370)), Institut national du sport, de l'expertise et de la performance (INSEP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Road cycling, Ergometry, Physical Therapy, Sports Therapy and Rehabilitation, 030229 sport sciences, 030204 cardiovascular system & hematology, Bicycling, [SHS]Humanities and Social Sciences, Power (physics), 03 medical and health sciences, 0302 clinical medicine, Power demand, Sprint, Statistics, Humans, Cycle ergometer, Orthopedics and Sports Medicine, Longitudinal Studies, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], ComputingMilieux_MISCELLANEOUS, Mathematics
Abstract: The aims of the present study were to characterize the mechanical output of final road sprints of an elite sprinter during international competitions in relation to his power-velocity-endurance characteristics, and to investigate the relationship between this sprint performance and the power produced during preceding phases of the race. The sprinter performed a set of short and long sprints (5 to 15 s) on a cycle ergometer to determine his maximal power-velocity-endurance profile. Based on eleven races, the distribution of power throughout each race, peak and mean power (Ppeak and Pmean ) and associated pedalling rates (vPpeak and vPmean ) during the final sprint were analyzed. The power-velocity-endurance profile of the sprinter indicated that his mean maximal power and corresponding optimal pedalling rate ranged from 20.1 W.kg-1 (124 rpm) for a 1-s sprint to 15.2 W.kg-1 (112 rpm) for 20 s. Race data showed that final road sprints were mainly performed on the ascending limb of the power-velocity relationship (vPpeak , 104±8 and vPmean , 101±8 rpm). Additionally, Ppeak and Pmean were lower than the theoretical maximal power determined from the power-velocity-endurance profile (10.4±7.0% and 11.2±9.2%, respectively), which highlighted a significant state of fatigue induced by the race. Finally, sprint power exhibited a high variability between races and was strongly related to the level of power produced during the last minute before the sprint. These findings show the importance of considering both the power-velocity-endurance qualities and the power demand of the last lead-up phase before the sprint in order to optimize final sprint performance.
Published: 2021

30. A polygenic risk score for multiple myeloma risk prediction

Author: Angelica Macauda, Matteo Pelosini, Krzysztof Jamroziak, Mario Petrini, Annette Juul Vangsted, Chiara Piredda, Stephane Minvielle, Marek Dudziński, Hervé Avet-Loiseau, Aleksandra Butrym, Ulla Vogel, Niels Abildgaard, Fabienne Lesueur, Waldemar Tomczak, Vibeke Andersen, Herlander Marques, Daniele Campa, Judit Várkonyi, Rui Manuel Reis, Katalin Kadar, Gabriele Buda, Małgorzata Raźny, Charles Dumontet, Juan Sainz, Anna Suska, Enrico Orciuolo, Agnieszka Druzd-Sitek, Marcin Kruszewski, Daria Zawirska, Niels Frost Andersen, Artur Jurczyszyn, Grzegorz Mazur, Marcin Rymko, Federica Gemignani, Edyta Subocz, Federico Canzian, Katia Beider, Jan Maciej Zaucha, Marzena Wątek, Arnon Nagler, Genomic Epidemiology Group [Heidelberg, Germany] (GEP / DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Pisa - Università di Pisa, University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland] (SUK), Aarhus University Hospital, Chaim Sheba Medical Center, Sea Hospital [Gdynia, Poland] (SH), Wroclaw Medical University [Wrocław, Pologne] (WMU), Hospices Civils de Lyon (HCL), Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Institute of Hematology and Transfusion Medicine [Warsaw, Poland] (IHTM), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Hospital Universitario Virgen de las Nieves [Granada, Spain] (HUVN), Semmelweis University [Budapest], Odense University Hospital (OUH), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Teaching Hospital No 1 [Rzeszów, Poland] (TH1), University of Copenhagen = Københavns Universitet (KU), Military Institute of Medicine [Warsaw, Poland] (MIM), Rydygier Specialistic Hospital [Cracow, Poland] (RSH), University of Minho [Braga], Jagiellonian University Medical College [Cracow, Poland] (JUMC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), The National Research Center for Work Environment [Copenhagen, Denmark] (NRCWE), University of Southern Denmark (SDU), ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal] (AL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Bydgoszcz [Bydgoszcz, Poland] (UHB), Medical University of Lublin, N. Copernicus Town Hospital [Torun, Poland] (NCTH), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), 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), Bernardo, Elizabeth, Wrocław Medical University, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), 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 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)
Subjects: Oncology, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), Multiple myeloma, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, business.industry, medicine.disease, Penetrance, 3. Good health, 030220 oncology & carcinogenesis, Polygenic risk score, Multiple Myeloma, business, Genome-Wide Association Study
Abstract: This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France
Published: 2021

31. IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals

Author: G. Pupillo, Mohamed A. Gizawy, Amir Reza Jalilian, Aruna Korde, Cyrille Alliot, Sandor Takacs, Katherine Gagnon, Joao A. Osso, Jeong H. Park, Kotaro Nagatsu, Mayeen Uddin Khandaker, Aleksander Bilewicz, Suzanne E. Lapi, Sudipta Chakarborty, Subhani Okarvi, Mohammad R.A. Rovais, Valeriia N. Starovoitova, Renata Mikolajczak, Abdul Hamid Al Rayyes, International Atomic Energy Agency [Vienna] (IAEA), Egyptian Atomic Energy Authority (EAEA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), GIPARRONAX [Saint-Herblain, France], Institute For Nuclear Research and Nuclear Energy (INRNE), Bulgarian Academy of Sciences (BAS), Bhabha Atomic Research Centre (BARC), Government of India, Department of Atomic Energy, Nuclear Science and Technology Research Institute [Tehran, Iran] (NSTRI), Istituto Nazionale di Fisica Nucleare (INFN), National Institutes for Quantum and Radiological Science and Technology (QST), Korea Atomic Energy Research Institute [Daejeon, south Korea] (KAERI), Sunway University [Malaysia], Radioisotope Centre POLATOM [Otwock, Pologne] (POLATOM), Institute of Nuclear Chemistry and Technology [Warsaw, Poland] (INCT), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Biacore/GE Healthcare [Uppsala], Atomic Energy Commission of Syria (AECS), Gouvernement de la Syrie, University of Alabama at Birmingham [ Birmingham] (UAB), and Bernardo, Elizabeth
Subjects: Pharmacology, Engineering, medicine.medical_specialty, 186Re, business.industry, theranostic, Member states, IAEA, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, research reactor, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, 47Sc, 67Cu, medicine, cyclotron, Radiology, Nuclear Medicine and imaging, Medical physics, CRP, business
Abstract: Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.
Published: 2021

32. Interest of the bc-GenExMiner web tool in oncology

Author: Hamza Lasla, Mario Campone, Philippe Juin, Pascal Jézéquel, Agnes Basseville, Fadoua Ben Azzouz, Wilfried Gouraud, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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 de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, SIRIC ILIAD [Angers, Nantes], and Bernardo, Elizabeth
Subjects: Prioritization, Oncology, Transcriptomique, Cancer Research, medicine.medical_specialty, Computer science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Web tool, Breast tumor, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Data visualization, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Statistical analysis, Web-based tool, Biomarker discovery, Transcriptomics, Cancer du sein, 030304 developmental biology, Outil web, 0303 health sciences, business.industry, Hematology, General Medicine, medicine.disease, Expression génique, 3. Good health, 030220 oncology & carcinogenesis, Gene expression, Web resource, business
Abstract: We are taking advantage of the launch of the latest version (v4.6) of our web-based data mining tool "breast cancer gene-expression miner" (bc-GenExMiner) to take stock of its position within the oncology research landscape and to present an activity report ten years after its establishment (http://bcgenex.ico.unicancer.fr). bc-GenExMiner is an open-access, user-friendly tool for statistical mining on breast tumor transcriptomes, annotated with more than 20 clinicopathologic and molecular characteristics. The database comprises more than 16,000 patients from 64 cohorts - including TCGA, METABRIC and SCAN-B - for whom several thousands of genes have been quantified by microarrays or RNA-seq. Correlation, expression and prognostic analyses are available for targeted, exhaustive or customized explorations of queried genes. bc-GenExMiner facilitates the validation, investigation, and prioritization of discoveries and hypotheses on genes of interest. It allows users to analyse large databases, create data visualizations, and obtain robust statistical analysis, thereby accelerating biomarker discovery. Ten years after its launch, judging by the number of visits, analyses, and scientific citations of bc-GenExMiner, we conclude that this web resource serves its purpose in the international scientific community working in breast cancer research, with a never-ending rise in its use., Nous profitons de l’occasion de la mise en ligne de la dernière version (v.4.6) de l’outil web breast cancer gene-expression miner (bc-GenExMiner) pour rappeler sa place dans le paysage de la recherche en oncologie et réaliser un bilan d’activité, dix ans après sa création (http://bcgenex.ico.unicancer.fr). bc-GenExMiner est un outil web de fouille statistique de données d’expressions géniques issues du criblage du transcriptome de tumeurs du sein annotées par une vingtaine de critères clinicopathologiques et moléculaires. Sa base de données inclut plus de 16 000 patientes issues de 64 cohortes, dont les cohortes METABRIC, SCAN-B et TCGA, pour lesquelles l’expression de plusieurs milliers de gènes a été mesurée par des puces à ADN ou par RNAseq. Il est composé de trois modules : « Corrélation », « Expression » et « Pronostic », qui permettent différentes sortes d’analyses. bc-GenExMiner offre aux chercheurs des possibilités de validation, d’exploration, de hiérarchisation d’hypothèses et de découverte concernant leurs gènes d’intérêt. Il permet de s’autonomiser par rapport à l’analyse de grandes bases de données, la production de figures, d’obtenir des résultats robustes et ainsi de gagner du temps pour la découverte de biomarqueurs. Dix ans après sa mise en ligne, à en juger par le nombre de visites, d’analyses et de citations de bc-GenExMiner dans des articles scientifiques, nous pouvons conclure que cet outil web sert la communauté scientifique internationale engagée dans la recherche sur le cancer du sein, et qu’il est de plus en plus utilisé.
Published: 2021

33. Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes

Author: Simon, Ville, Marine, Lorent, Clarisse, Kerleau, Anders, Asberg, Christophe, Legendre, Emmanuel, Morelon, Fanny, Buron, Valérie, Garrigue, Moglie, Le Quintrec, Sophie, Girerd, Marc, Ladrière, Laetitia, Albano, Antoine, Sicard, Denis, Glotz, Carmen, Lefaucheur, Julien, Branchereau, David, Jacobi, Magali, Giral, Etienne, Sicard, Institut de Transplantation et de Recherche en Transplantation [CHU Nantes] (ITERT), Centre hospitalier universitaire de Nantes (CHU Nantes), European cohort for Kidney Transplantation Epidemiology (EKiTE), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Oslo University Hospital [Oslo], Réseau CENTAURE, Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lapeyronie [Montpellier] (CHU), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Service d'Urologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), and Salvy-Córdoba, Nathalie
Subjects: Graft Rejection, Male, Time Factors, Databases, Factual, Epidemiology, Kidney, Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Organ transplantation, MESH: Kidney Transplantation, MESH: Delayed Graft Function, Kidney transplantation / nephrology, MESH: Incidence, Prospective Studies, Kidney transplantation, MESH: Aged, MESH: Middle Aged, Norway, Ischemia-reperfusion, Incidence, Graft Survival, Hazard ratio, Middle Aged, Constriction, medicine.anatomical_structure, Nephrology, Cardiology, Female, France, Adult, medicine.medical_specialty, MESH: Circadian Clocks, MESH: Graft Survival, Delayed Graft Function, MESH: Graft Rejection, Cadaver organ transplantation, MESH: Norway, Circadian Clocks, Internal medicine, medicine, Humans, Circadian rhythm, Aged, Transplantation, MESH: Humans, business.industry, MESH: Time Factors, MESH: Adult, Original Articles, Odds ratio, medicine.disease, Organ transplant, MESH: Databases, Factual, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, MESH: Male, MESH: Prospective Studies, Confidence interval, MESH: France, business, MESH: Female
Abstract: International audience; Background and objectives The fact that metabolism and immune function are regulated by an endogenous molecular clock that generates circadian rhythms suggests that the magnitude of ischemia reperfusion, and subsequent inflammation on kidney transplantation, could be affected by the time of the day. Design, setting, participants, & measurements We evaluated 5026 individuals who received their first kidney transplant from deceased heart-beating donors. In a cause-specific multivariable analysis, we compared delayed graft function and graft survival according to the time of kidney clamping and declamping. Participants were divided into those clamped between midnight and noon ( ante meridiem [ am ] clamping group; 65%) or clamped between noon and midnight ( post meridiem [ pm ] clamping group; 35%), and, similarly, those who underwent am declamping (25%) or pm declamping (75%). Results Delayed graft function occurred among 550 participants (27%) with am clamping and 339 (34%) with pm clamping (adjusted odds ratio, 0.81; 95% confidence interval, 0.67 to 0.98; P =0.03). No significant association was observed between clamping time and overall death-censored graft survival (hazard ratio, 0.92; 95% confidence interval, 0.77 to 1.10; P =0.37). No significant association of declamping time with delayed graft function or graft survival was observed. Conclusions Clamping between midnight and noon was associated with a lower incidence of delayed graft function, whereas declamping time was not associated with kidney graft outcomes.
Published: 2021

34. Biological differences between two commercial anti-CD19 CAR T cells products and impact on outcomes in lymphoma patients

Author: Tessoulin, Benoit, Grain, Audrey, Ollier, Jocelyn, Gastinne, Thomas, Dubruille, Viviane, Mahé, Béatrice, Blin, Nicolas, Lok, Anne, Vantyghem, Sophie, Sortais, Clara, Touzeau, Cyrille, Moreau, Philippe, Le Gouill, Steven, Chevallier, Patrice, Clémenceau, Béatrice, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Département d'Hématologie Clinique [CHU Nantes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), university hospital, University Hospital, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), and Ollier, Jocelyn
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience
Published: 2022

35. BR-NPA: A non-parametric high-resolution attention model to improve the interpretability of attention

Author: Tristan Gomez, Suiyi Ling, Thomas Fréour, Harold Mouchère, Nantes Université - Ecole Polytechnique de l'Université de Nantes (Nantes Univ - EPUN), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes Université - École Centrale de Nantes (Nantes Univ - ECN), and Gomez, Tristan
Subjects: FOS: Computer and information sciences, [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], Computer Science - Machine Learning, Artificial Intelligence, Computer Vision and Pattern Recognition (cs.CV), Signal Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Vision and Pattern Recognition, Software, Machine Learning (cs.LG), [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience; The prevalence of employing attention mechanisms has brought along concerns about the interpretability of attention distributions. Although it provides insights into how a model is operating, utilizing attention as the explanation of model predictions is still highly dubious. The community is still seeking more interpretable strategies for better identifying local active regions that contribute the most to the final decision. To improve the interpretability of existing attention models, we propose a novel Bilinear Representative Non-Parametric Attention (BR-NPA) strategy that captures the task-relevant human-interpretable information. The target model is first distilled to have higher-resolution intermediate feature maps. From which, representative features are then grouped based on local pairwise feature similarity, to produce finer-grained, more precise attention maps highlighting task-relevant parts of the input. The obtained attention maps are ranked according to the activity level of the compound feature, which provides information regarding the important level of the highlighted regions. The proposed model can be easily adapted in a wide variety of modern deep models, where classification is involved. Extensive quantitative and qualitative experiments showcase more comprehensive and accurate visual explanations compared to state-of-the-art attention models and visualization methods across multiple tasks including fine-grained image classification, few-shot classification, and person re-identification, without compromising the classification accuracy. The proposed visualization model sheds imperative light on how neural networks ‘pay their attention’ differently in different tasks.
Published: 2022

36. Cervical cancer screening uptake: A randomized controlled trial assessing the effect of sending invitation letters to non-adherent women combined with sending their general practitioners a list of their non-adherent patients (study protocol)

Author: Delphine, Teigné, Anne-Sophie, Banaszuk, Charlotte, Grimault, Linda, Abes, Aurélie, Gaultier, Cédric, Rat, Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Régional de Coordination des Dépistages des Cancers [Angers] (CRCDC Pays de la Loire), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Pecqueret, Valérie
Subjects: screening uptake, [SDV]Life Sciences [q-bio], organized screening programmes, Public Health, Environmental and Occupational Health, Uterine Cervical Neoplasms, randomized controlled clinical trial (RCT), [SDV] Life Sciences [q-bio], cervical cancer screening (CCS), general practitioners, Humans, Patient Compliance, Mass Screening, Female, Early Detection of Cancer, Randomized Controlled Trials as Topic
Abstract: IntroductionCervical cancer (CC) is the fourth most common cancer among women. It can be cured if diagnosed at an early stage and treated promptly. The World Health Organization suggests that 70% of women should be screened with a high-performance test by the age of 35. This paper reports a protocol to assess the effect of two modalities of organized CC screening programmes on CC screening uptake.Methods and analysisDesign and setting: The design involves a 3-arm randomized controlled study performed in a French geographic area on the west coast. A total of 1,395 general practitioners will be randomized, depending on their general practice surgeries. Participants: The design is based on a total of 94,393 women aged 40 to 65 years who are eligible for CC screening. Intervention: In the “optimized cancer screening” group, the intervention will combine sending invitation letters to non-adherent women with sending general practitioners (GPs) a list of their non-adherent patients. In the “standard cancer screening” group, the intervention will be limited to sending invitation letters to non-adherent women. In the “usual care” group, no letter will be sent either to women or to their GPs. Primary endpoint: CC screening test uptake will be assessed after a 6-month follow-up period. Statistical analysis: The percentage of women who are up-to-date with their screening at 6 months after the intervention will be compared across arms using a generalized mixed linear model.DiscussionA large-scale randomized trial of this nature is unprecedented. The study will enable us to assess a strategy relying on GPs, identified as the coordinators in this screening strategy. The study results should help policy makers to implement organized CC screening programs in the future.Ethics and disseminationThe study was approved was approved by the Ethics Committee of the National College of Teaching General practitioners (IRB00010804). It was recorded in ClinicalTrials.gov on the number NCT04689178 (28 December 2020). The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.
Published: 2022

37. Linking Biomedical Data Warehouse Records With the National Mortality Database in France: Large-scale Matching Algorithm

Author: Vianney Guardiolle, Adrien Bazoge, Emmanuel Morin, Béatrice Daille, Delphine Toublant, Guillaume Bouzillé, Youenn Merel, Morgane Pierre-Jean, Alexandre Filiot, Marc Cuggia, Matthieu Wargny, Antoine Lamer, Pierre-Antoine Gourraud, 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), cluster DELPHI - NExT - French National Research Agency (Agence Nationale de la Recherche, ANR), Region Pays de la Loire, Nantes Metropoles, and ANR-20-THIA-0011,AIby4,AI by / for Human, Health and Industry(2020)
Subjects: clinical data warehouse, medical record linkage, Health Information Management, clinical informatics, data reuse, open data, Health Informatics, [SDV.IB]Life Sciences [q-bio]/Bioengineering, data warehousing, medical informatics applications, French National Mortality Database
Abstract: Background Often missing from or uncertain in a biomedical data warehouse (BDW), vital status after discharge is central to the value of a BDW in medical research. The French National Mortality Database (FNMD) offers open-source nominative records of every death. Matching large-scale BDWs records with the FNMD combines multiple challenges: absence of unique common identifiers between the 2 databases, names changing over life, clerical errors, and the exponential growth of the number of comparisons to compute. Objective We aimed to develop a new algorithm for matching BDW records to the FNMD and evaluated its performance. Methods We developed a deterministic algorithm based on advanced data cleaning and knowledge of the naming system and the Damerau-Levenshtein distance (DLD). The algorithm’s performance was independently assessed using BDW data of 3 university hospitals: Lille, Nantes, and Rennes. Specificity was evaluated with living patients on January 1, 2016 (ie, patients with at least 1 hospital encounter before and after this date). Sensitivity was evaluated with patients recorded as deceased between January 1, 2001, and December 31, 2020. The DLD-based algorithm was compared to a direct matching algorithm with minimal data cleaning as a reference. Results All centers combined, sensitivity was 11% higher for the DLD-based algorithm (93.3%, 95% CI 92.8-93.9) than for the direct algorithm (82.7%, 95% CI 81.8-83.6; P98% in all subgroups. Our algorithm matched tens of millions of death records from BDWs, with parallel computing capabilities and low RAM requirements. We used the Inseehop open-source R script for this measurement. Conclusions Overall, sensitivity/recall was 11% higher using the DLD-based algorithm than that using the direct algorithm. This shows the importance of advanced data cleaning and knowledge of a naming system through DLD use. Statistically significant differences in sensitivity between groups could be found and must be considered when performing an analysis to avoid differential biases. Our algorithm, originally conceived for linking a BDW with the FNMD, can be used to match any large-scale databases. While matching operations using names are considered sensitive computational operations, the Inseehop package released here is easy to run on premises, thereby facilitating compliance with cybersecurity local framework. The use of an advanced deterministic matching algorithm such as the DLD-based algorithm is an insightful example of combining open-source external data to improve the usage value of BDWs.
Published: 2022

38. Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment

Author: Thibault Comont, Amandine Dernoncourt, Antoinette Perlat, Stéphane Cheze, Bernard Bonnotte, O. Souchaud-Debouverie, Pierre-Yves Jeandel, Bertrand Godeau, Jean-François Viallard, Jean-Christophe Lega, Delphine Gobert, Marc Michel, Mikael Ebbo, Corentin Orvain, Julie Graveleau, Antoine Dossier, Nathalie Costedoat-Chalumeau, Marc Ruivard, Louis Terriou, Arthur Mageau, CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des cytopénies auto-immunes [CHU Mondor] (CeReCAI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lille, CHU Lille, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier de Saint-Nazaire, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Hôpital l'Archet, Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bernardo, Elizabeth, CHU Henri Mondor [Créteil], 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: Adult, Male, Thrombopoietin Receptor Agonists, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Medicine, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic, business.industry, Retrospective cohort study, Hematology, Middle Aged, Immune thrombocytopenia, Treatment Outcome, Curative treatment, Sustained response, Female, Rituximab, business, Receptors, Thrombopoietin, medicine.drug
Abstract: Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicentre retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-Ras that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs. This article is protected by copyright. All rights reserved.
Published: 2021

39. Type 2 immunity‐driven diseases: Towards a multidisciplinary approach

Author: Hassoun, Dorian, Malard, Olivier, Barbarot, Sébastien, Magnan, Antoine O., Colas, Luc, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Fondation pour la Recherche Médicale, FRM: FDM201906008829, Centre Hospitalier Universitaire de Nantes, CHU de Nantes, This project was supported by Sanofi-Aventis France. This work was also supported by ??l'institut de Recherche en Sant? Respiratoire des Pays de la Loire? (IRSRPL) and by ??l?Appel d?Offre Interne? of CHU de Nantes through the ICART project. DH wants to thank the Fondation pour la Recherche M?dicale, which funded his PhD (FDM201906008829). Luc Colas thanks GlaxoSmithKline who funded his PhD., This project was supported by Sanofi‐Aventis France. This work was also supported by « l'institut de Recherche en Santé Respiratoire des Pays de la Loire» (IRSRPL) and by « l’Appel d’Offre Interne» of CHU de Nantes through the ICART project., DH wants to thank the Fondation pour la Recherche Médicale, which funded his PhD (FDM201906008829). Luc Colas thanks GlaxoSmithKline who funded his PhD., Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and HAL UVSQ, Équipe
Subjects: [SDV]Life Sciences [q-bio], Immunology, Eczema, medicine.disease_cause, Dermatitis, Atopic, Unmet needs, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Humans, Immunology and Allergy, Medicine, Type 2 immunity, 030304 developmental biology, Asthma, 0303 health sciences, Innate immune system, business.industry, Atopic dermatitis, Immune dysregulation, medicine.disease, Phenotype, Immunity, Innate, 3. Good health, [SDV] Life Sciences [q-bio], 030228 respiratory system, Cytokines, business
Abstract: International audience; Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL-4, IL-5, IL-13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2-targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field.
Published: 2021

40. Different number of circulating CD34 + cells in essential thrombocythemia, prefibrotic/early primary myelofibrosis, and overt primary myelofibrosis

Author: Valérie Ugo, Marie-Christine Rousselet, Damien Luque Paz, Laurane Cottin, Eric Lippert, Barbara Burroni, Françoise Boyer, Corentin Orvain, Franck Geneviève, Jean-Christophe Ianotto, Jean-Baptiste Robin, Charles Bescond, Mathilde Hunault-Berger, Isabelle Quintin-Roué, Laboratoire d'Hématologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], Département d'anatomopathologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and LUQUE PAZ, DAMIEN
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, medicine.medical_specialty, Hematology, Primary (chemistry), business.industry, Essential thrombocythemia, Cd34 cells, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, medicine.disease, Polycythemia vera, Bone Marrow, Primary Myelofibrosis, Internal medicine, medicine, Humans, Myeloproliferative Neoplasms, Essential Thrombocythemia, business, Myelofibrosis, ComputingMilieux_MISCELLANEOUS, Thrombocythemia, Essential
Abstract: International audience; No abstract available
Published: 2021

41. Place de l’imagerie moléculaire dans la prise en charge du cancer de la prostate

Author: Bruno Maucherat, Mathieu Frindel, Caroline Rousseau, Vincent Fleury, M. Le Thiec, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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 de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CRLCC René Gauducheau, and Bernardo, Elizabeth
Subjects: Initial staging, Mri imaging, Disease detection, PET/CT, [SDV.CAN]Life Sciences [q-bio]/Cancer, Next generation imaging, Imagerie de nouvelle génération, Management of prostate cancer, Prostate cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, Stadification, Prostate, Medicine, Radiology, Nuclear Medicine and imaging, Stage (cooking), business.industry, medicine.disease, Innovative Therapies, medicine.anatomical_structure, Oncology, Psma pet, Récidive, Cancer de prostate, business, Nuclear medicine, TEP/TDM
Abstract: International audience; In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging.
Published: 2021

42. Risk of symptomatic venous thromboembolism in mild and moderate COVID-19: A comparison of two prospective European cohorts

Author: Jérémie Riou, Rafael Mahieu, Dominique Savary, Pierre-Marie Roy, Caroline Soulie, Delphine Douillet, Francois Morin, A Penaloza, Thomas Moumneh, UCL - SSS/IREC/EPID - Pôle d'épidémiologie et biostatistique, UCL - (SLuc) Service des urgences, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Université d'Angers (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales [SFR ICAT - UA] (PRISM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), French Clinical Research Infrastructure Network on Venous Thromboembolism (FCRIN INNOVTE), Chard-Hutchinson, Xavier, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales (PRISM [SFR ICAT - UA]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and 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)
Subjects: medicine.medical_specialty, Deep vein, [SDV]Life Sciences [q-bio], VTE risk, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Full Length Article, medicine, Humans, Prospective Studies, cardiovascular diseases, Prospective cohort study, 030304 developmental biology, Aged, Retrospective Studies, 0303 health sciences, business.industry, SARS-CoV-2, Incidence (epidemiology), SARS-CoV-2 infection, COVID-19, Hematology, Emergency department, Venous Thromboembolism, medicine.disease, Thrombosis, 3. Good health, Pulmonary embolism, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Cohort, Propensity score matching, business, Venous thromboembolism
Abstract: International audience; Background: Severely ill patients with SARS-CoV-2 have an increased risk of venous thromboembolism (VTE) i.e., deep vein thrombosis and pulmonary embolism. However, the VTE risk in patients with mild and moderate COVID-19, hospitalized or managed at home, remain uncertain. The aims of this study were to assess the rate and the risk factors symptomatic VTE, in patients with mild and moderate COVID-19 and to compare them to a cohort of similar patients without COVID-19. Methods: Patients presenting to the emergency department (ED) of participating centers for confirmed or probable mild or moderate COVID-19 and not having acute VTE were included. This COVID-19 cohort was retrospectively compared to a prospective cohort of similar ED patients using propensity score matching. The main outcome was the rate of symptomatic VTE within the 28 days after ED presentation. Results: A total of 2292 patients were included in the COVID-19 cohort. The 28-day incidence of symptomatic VTE was 1.3% (n = 29/2292, 95%CI: 0.9 to 1.8), 2.3% (n = 20/866, 95%CI: 1.5 to 3.5) in moderate COVID-19 patients and 0.6% (n = 9/1426; 95%CI: 0.3 to 1.2) in mild COVID-19 patients managed as outpatients. An age over 65 years and hospitalization were independent risk factors of VTE. After adjustment, patients in the COVID19 cohort had an absolute increase in over symptomatic VTE risk of +1.69% (95%CI, 0.88 to 2.51) versus patients in the comparison cohort (n = 1539). Conclusions: Patients with moderate COVID-19 presenting to the ED had a high risk of subsequent VTE. Trial registration: Ethics committee of the CHU of Angers (N degrees 2020/87).
Published: 2021

43. Segmental contribution to whole-body angular momentum during stepping in healthy young and old adults

Author: Nicolas A. Turpin, Angélique Lesport, Teddy Caderby, Jérémie Begue, Bruno Watier, Nicolas Peyrot, Georges Dalleau, Ingénierie, Recherche et Intervention, Sport Santé et Environnement (IRISSE), Université de La Réunion (UR), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Le Mans Université (UM), Équipe Mouvement des Systèmes Anthropomorphes (LAAS-GEPETTO), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), and Université de Toulouse (UT)
Subjects: Male, medicine.medical_specialty, Angular momentum, Aging, Science, H control, 030209 endocrinology & metabolism, Kinematics, Walking, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Postural Balance, Balance (ability), Mathematics, Aged, Leg, Multidisciplinary, Health care, Torso, Middle Aged, Trunk, Sagittal plane, Biomechanical Phenomena, medicine.anatomical_structure, Risk factors, Arm, Medicine, Female, Rotational dynamics, Whole body, Biomedical engineering, 030217 neurology & neurosurgery
Abstract: Recent evidence suggests that during volitional stepping older adults control whole-body angular momentum (H) less effectively than younger adults, which may impose a greater challenge for balance control during this task in the elderly. This study investigated the influence of aging on the segment angular momenta and their contributions to H during stepping. Eighteen old and 15 young healthy adults were instructed to perform a series of stepping at two speed conditions: preferred and as fast as possible. Full-body kinematics were recorded to compute angular momenta of the trunk, arms and legs and their contributions to total absolute H on the entire stepping movement. Results indicated that older adults exhibited larger angular momenta of the trunk and legs in the sagittal plane, which contributed to a higher sagittal plane H range during stepping compared to young adults. Results also revealed that older adults had a greater trunk contribution and lower leg contribution to total absolute H in the sagittal plane compared to young adults, even though there was no difference in the other two planes. These results stress that age-related changes in H control during stepping arise as a result of changes in trunk and leg rotational dynamics.
Published: 2021

44. LentiRILES, a miRNA-ON sensor system for monitoring the functionality of miRNA in cancer biology and therapy

Author: David Gosset, Loris Roncali, Yoan Laurent, Chantal Pichon, Flora Reverchon, Emmanuel Garcion, Patrick Baril, Audrey Rousseau, Francisco Martin, Patrick Midoux, Claire Loussouarn, Viorel Simion, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), 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), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Inca : PL-BIO 2014–2020 (consortium Marengo)Ligue Contre le Cancer [Région du Loiret : 2017-2019]ARD 2020 Biopharmaceuticals [RNA cell factory 2017-2020], ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-19-ENM3-0003,GLIOSILK,Silk-fibroin interventional nano-trap for the treatment of glioblastoma.(2019), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université 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), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Silk-fibroin interventional nano-trap for the treatment of glioblastoma. - - GLIOSILK2019 - ANR-19-ENM3-0003 - Euronanomed III - VALID
Subjects: Male, Cell, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biosensing Techniques, Mice, SCID, Computational biology, Biology, Cell therapy, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Genes, Reporter, microRNA, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Animals, Humans, Luciferase, Molecular Biology, Gene, Cell Proliferation, miRNA, 030304 developmental biology, 0303 health sciences, Technical Paper, Cell Cycle, Lentivirus, glioblastoma, RNA therapeutics, Cell Biology, Middle Aged, molecular imaging, RILES, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Luminescent Measurements, Female, Molecular imaging, Function (biology), Intracellular
Abstract: International audience; A major unresolved challenge in miRNA biology is the capacity to monitor the spatiotemporal activity of miRNAs expressed in animal disease models. We recently reported that the miRNA-ON monitoring system called RILES (RNAi-inducible expression Luciferase system) implanted in lentivirus expression system (LentiRILES) offers opportunity to decipher the kinetics of miRNA activity in vitro, in relation with their intracellular trafficking in glioblastoma cells. In this study we describe in detail the method for production of LentiRILES stable cell lines and employed it in several applications in the field of miRNA biology and therapy. We show that LentiRILES is a robust, highly specific and sensitive miRNA sensor system that can be used in vitro as a single-cell miRNA monitoring method, cell-based screening platform for miRNA therapeutics and as a tool to analyze the structurefunction relationship of the miRNA duplex. Furthermore, we report the kinetic of miRNA activity upon the intracranial delivery of miRNA mimics in an orthotopic animal model of glioblastoma. This information is exploited to evaluate the tumor suppressive function of miRNA-200c as locoregional therapeutic modality to treat glioblastoma. Our data provide evidence that LentiRILES is a robust system, well-suited to resolve the activity of endogenous and exogenously expressed miRNAs for basic research to gene and cell therapy.
Published: 2021

45. ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

Author: Anne-Gaëlle Rio, Zi-Ling Liu, Virginie Gandemer, Aurélien A. Sérandour, Benoit Soubise, Marie-Dominique Galibert, Hana Raslova, Jason S. Carroll, Laurent Corcos, Jocelyne Demengeot, Nathalie Douet-Guilbert, Lydie Debaize, Jérémie Rouger-Gaudichon, Marie-Bérengère Troadec, Gilles Salbert, Yan Jiang, David Gilot, Hélène Jakobczyk, Stéphane Avner, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Jilin University (JLU), 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni] (CRUK), University of Cambridge [UK] (CAM), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Ligue Regionale contre le cancerLigue nationale contre le cancer [22, 29, 35, 56, 79, 41], Region Bretagne Region Bretagne, Societe Francaise d'Hematologie, Rennes Metropole Region Bretagne, societe francaise de lutte contre les cancers et les leucemies de l'enfant et de l'adolescent, Federation Enfants et Sante, AVIESAN Plan Cancer, Halte au Cancer, Association Gaetan Saleun, Mrs. M-Dominique Blanc-Bert, Canceropole Grand Ouest, Societe Francaise de Biochimie et Biologie Moleculaire, People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme [291851], European Project: 291851,EC:FP7:PEOPLE,FP7-PEOPLE-2011-CIG,ALLRUN(2012), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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 de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chard-Hutchinson, Xavier, and Modeling TEL/AML1 childhood lymphoblastic leukemia in zebrafish - ALLRUN - - EC:FP7:PEOPLE2012-02-01 - 2016-01-31 - 291851 - VALID
Subjects: Cancer Research, Letter, Oncogene Proteins, Fusion, [SDV]Life Sciences [q-bio], Recombination-activating gene, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Etv6 runx1, Tumor Cells, Cultured, Humans, Leukaemia, Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Homeodomain Proteins, 0303 health sciences, Gene Expression Regulation, Leukemic, business.industry, Hematology, B-cell acute lymphoblastic leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, [SDV] Life Sciences [q-bio], Cell Transformation, Neoplastic, Oncology, RUNX1, chemistry, 030220 oncology & carcinogenesis, Core Binding Factor Alpha 2 Subunit, Cancer research, business, Haematological diseases
Abstract: Funder: Société Française de Biochimie et Biologie Moléculaire ; French Research Ministry, Funder: Cancéropole Grand Ouest ; Région Bretagne ; Société Française d’Hématologie, Funder: Ligue Régionale contre le cancer, ETV6-RUNX1 and RUNX1 directly promote RAG1 expression. ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of RAG1 and the −80 bp promoter of RAG1 gene respectively, and compete for these bindings. ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity. ETV6-RUNX1 participates directly in two events of the multi-hit ALL leukemogenesis: as an initiating event and as an activator of RAG1 expression.
Published: 2021

46. Correlation between magnetic resonance, X-ray imaging alterations and histological changes in an ovine model of age-related disc degeneration

Author: Bouhsina, N, Decante, C, Hardel, J, Madec, S, Abadie, J, Hamel, A, Le Visage, C, Lesoeur, J, Guicheux, J, Clouet, J, Fusellier, M, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes - UFR Odontologie, Université de Nantes (UN), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Femme, Enfant, Adolescent [CHU Nantes] (Pôle hospitalo-universitaire PHU5 - FEA), Centre hospitalier universitaire de Nantes (CHU Nantes), Animaux modèles pour la recherche en oncologie comparée (AMaROC), 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), Ostéo-articulaire - Tête et cou - Odontologie - Neurochirurgie - Neurotraumatologie [CHU Nantes] (Pôle hospitalo-universitaire PHU4 - OTONN), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Santé Publique, Pharmacie et Prévention [CHU Nantes] (Pôle hospitalo-universitaire PHU11 - S3P), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), 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), and Jehan, Frederic
Subjects: [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], sheep, Lumbar Vertebrae, Magnetic Resonance Spectroscopy, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, RD1-811, X-Rays, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, x-ray imaging, degeneration, Intervertebral Disc Degeneration, Diseases of the musculoskeletal system, histology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, RC925-935, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, magnetic resonance imaging, Female, intervertebral disc, Surgery
Abstract: International audience; Sheep are one of the many animal models used to investigate the pathophysiology of disc degeneration and the regenerative strategies for intervertebral disc (IVD) disease. To date, few studies have thoroughly explored ageing of ovine lumbar IVDs. Hence, the objective of the present study was to concomitantly assess the development of spontaneous age-related lumbar IVD degeneration in sheep using X-ray, magnetic resonance imaging (MRI) as well as histological analyses. 8 young ewes (< 48 months old) and 4 skeletally mature ewes (> 48 months old) were included. Disc height, Pfirrmann and modified Pfirrmann grades as well as T2-wsi and T2 times were assessed by X-ray and MRI. The modified Boos score was also determined using histology sections. Pfirrmann (2 to 3) and modified Pfirrmann (2 to 4) grades as well as Boos scores (7 to 13) gradually increased with ageing, while T2-weighted signal intensity (1.18 to 0.75), T2 relaxation time (114.36 to 70.65 ms) and disc height (4.1 to 3.2 mm) decreased significantly. All the imaging modalities strongly correlated with the histology (p < 0.0001). The present study described the suitability of sheep as a model of age-related IVD degeneration by correlation of histological tissue alterations with the changes observed using X-ray and MRI. Given the structural similarities with humans, the study demonstrated that sheep warrant being considered as a pertinent animal model to investigate IVD regenerative strategies without induction of degeneration.
Published: 2021

47. Advances in the Chemistry of Astatine and Implications for the Development of Radiopharmaceuticals

Author: Gilles Montavon, François Guérard, Jean-François Gestin, Nicolas Galland, Romain Eychenne, Lu Liu, Clémence Maingueneau, Nuclear Oncology (CRCINA-ÉQUIPE 13), 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), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), GIPARRONAX [Saint-Herblain, France], Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), INCa-DGOSInserm_12558, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), 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), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Guérard, François, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID
Subjects: Halogen bond, 010405 organic chemistry, [SDV]Life Sciences [q-bio], chemistry.chemical_element, General Medicine, General Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, 13. Climate action, Computational chemistry, Electrophile, Halogen, Nucleophilic substitution, Fluorine, Molecule, Earth (chemistry), Astatine, ComputingMilieux_MISCELLANEOUS
Abstract: ConspectusAstatine (At) is the rarest on Earth of all naturally occurring elements, situated below iodine in the periodic table. While only short-lived isotopes (t1/2 ≤ 8.1 h) are known, 211At is the object of growing attention due to its emission of high-energy alpha particles. Such radiation is highly efficient to eradicate disseminated tumors, provided that the radionuclide is attached to a cancer-targeting molecule. The interest in applications of 211At in nuclear medicine translates into the increasing number of cyclotrons able to produce it. Yet, many challenges related to the minute amounts of available astatine are to be overcome in order to characterize its physical and chemical properties. This point is of paramount importance to develop synthetic strategies and solve the labeling instability in current approaches that limits the use of 211At-labeled radiopharmaceuticals. Despite its discovery in the 1940s, only the past decade has seen a significant rise in the understanding of astatine's basic chemical and radiochemical properties, thanks to the development of new analytical and computational tools.In this Account, we give a concise summary of recent advances in the determination of the physicochemical properties of astatine, putting in perspective the duality of this element which exhibits the characteristics both of a halogen and of a metal. Striking features were evidenced in the recent determination of its Pourbaix diagram such as the identification of stable cationic species, At+ and AtO+, contrasting with other halogens. Like metals, these species were shown to form complexes with anionic ligands and to exhibit a particular affinity for organic species bearing soft donor atoms. On the other hand, astatine shares many characteristics with other halogen elements. For instance, the At- species exists in water, but with the least range of EH-pH stability in the halogen series. Astatine can form molecular interactions through halogen bonding, and it was only recently identified as the strongest halogen-bond donor. This ability is nonetheless affected by relativistic effects, which translate to other peculiarities for this heavy element. For instance, the spin-orbit coupling boosts astatine's propensity to form charge-shift bonds, catching up with the behavior of the lightest halogens (fluorine, chlorine).All these new data have an impact on the development of radiolabeling strategies to turn 211At into radiopharmaceuticals. Inspired by the chemistry of iodine, the chemical approaches have sparsely evolved over the past decades and have long been limited to electrophilic halodemetalation reactions to form astatoaryl compounds. Conversely, recent developments have favored the use of the more stable At- species including the aromatic nucleophilic substitution with diaryliodonium salts or the copper-catalyzed halodeboronation of arylboron precursors. However, it is clear that new bonding modalities are necessary to improve the in vivo stability of 211At-labeled aryl compounds. The tools and data gathered over the past decade will contribute to instigate original strategies for overcoming the challenges offered by this enigmatic element. Alternatives to the C-At bond such as the B-At and the metal-At bonds are typical examples of exciting new axes of research.
Published: 2021

48. Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

Author: Catherine Willem, Zakia Djaoud, Thierry Guillaume, Gaëlle David, Nolwenn Legrand, Patrice Chevallier, Katia Gagne, Alexandre Walencik, Christelle Retière, Pierre Mérieau, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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), EFS Centre-Pays de la Loire [Nantes], Bernardo, Elizabeth, 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), and 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)
Subjects: Cyclophosphamide, medicine.medical_treatment, T cell, T-Lymphocytes, Science, Cell, Immunology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Hematopoietic stem cell transplantation, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immune Reconstitution, [SDV.CAN] Life Sciences [q-bio]/Cancer, Receptors, KIR, Recurrence, immune system diseases, medicine, Humans, Receptor, 030304 developmental biology, Cancer, Interleukin-15, 0303 health sciences, Multidisciplinary, Hematopoietic Stem Cell Transplantation, In vitro, Killer Cells, Natural, medicine.anatomical_structure, Receptors, KIR2DL3, Transplantation, Haploidentical, Medicine, 030215 immunology, medicine.drug
Abstract: KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+target cells. The association of KIR+T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT.
Published: 2021

49. Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder

Author: Renaud de Crevoisier, David Azria, Christophe Hennequin, Jonathan Khalifa, Pierre Graff-Cailleaud, Igor Latorzeff, Gilles Créhange, Pierre Blanchard, Arnaud Mejean, Nicolas Magné, Morgane Cabaillé, Olivier Riou, Morgan Rouprêt, Géraldine Pignot, S. Belhomme, Olivier Chapet, Paul Sargos, Stéphane Culine, David Pasquier, Stéphane Supiot, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Department of Radiotherapy, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), 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 Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Clinique Pasteur [Toulouse], Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Guidelines, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, Adaptive radiotherapy, Adaptative radiotherapy, Urothelial carcinoma, Image-guided radiation therapy, Carcinoma, Transitional Cell, Bladder cancer, Image guided radiation therapy, Radiotherapy, business.industry, Radiotherapy Planning, Computer-Assisted, Standard treatment, Radiotherapy Dosage, Radical radiotherapy, Hematology, medicine.disease, Clinical trial, Radiation therapy, Urinary Bladder Neoplasms, Oncology, 030220 oncology & carcinogenesis, Radiotherapy, Intensity-Modulated, Trimodal therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Radiotherapy, Image-Guided
Abstract: International audience; Purpose: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.Methods and materials: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.Results: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.Conclusion: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.
Published: 2021

50. Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study

Author: Galiñanes, Manuel, Casós, Kelly, Blasco-Lucas, Arnau, Permanyer, Eduard, Máñez, Rafael, Le Tourneau, Thierry, Barquinero, Jordi, Schwartz, Simon, Bottio, Tomaso, Roussel, Jean Christian, Fellah-Hebia, Imen, Sénage, Thomas, Evangelista Masip, Arturo, Badano, Luigi P., Ruiz-Majoral, Alejandro, Galli, Cesare, Padler-Karavani, Vered, Soulillou, Jean-Paul, Vidal Guitart, Xavier, Cozzi, Emanuele, Costa, Cristina, Universitat Autònoma de Barcelona, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], Vall d’Hebron Research Institute (VHIR), Llobregat Hospital [Barcelona], Quironsalud Teknon Heart Institute [Barcelona, Spain] (QTHI), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Bellvitge University Hospital [Barcelona, Spain], Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Università degli Studi di Padova = University of Padua (Unipd), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Avantea [Cremona, Italy], Tel Aviv University (TAU), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Institut Català de la Salut [Barcelona, Spain] (ICS), L’Hospitalet de Llobregat [Barcelona, Spain], The project was funded by the European Commission (FP7/2007–2013, Grant Agreement 603049: accessed on 1 September 2013, and PERIS SLT002/16/00445 funded by the Department of Health of the Generalitat de Catalunya, both granted to C.C., and cofunded by FEDER funds, a way to build Europe. IDIBELL benefits from the support of CERCA., European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), 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), KERANDEL-DION, Céline, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Galinanes, M, Casos, K, Blasco-Lucas, A, Permanyer, E, Manez, R, Le Tourneau, T, Barquinero, J, Schwartz, S, Roussel, T, Fellah-Hebia, I, Senage, T, Evangelista, A, Badano, L, Ruiz-Majoral, A, Galli, C, Padler-Karavani, V, Soulillou, J, Vidal, X, Cozzi, E, and Costa, C
Subjects: Estrès oxidatiu, [SDV]Life Sciences [q-bio], Structural valve deterioration, Lipid peroxidation, Prosthesis Design, Biochemistry, structural valve deterioration, aortic valve, biological heart valves, lipid peroxidation, oxidative stress, protein nitration, transcatheter aortic valve implantation, Humans, Aortic valve, Molecular Biology, Heart valve prosthesis, Heart valves, oxidative stre, Transcatheter aortic valve implantation, Pròtesis valvulars cardíaques, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Aortic Valve Stenosis, Vàlvules cardíaques, biological heart valve, Prosthesis Failure, [SDV] Life Sciences [q-bio], Treatment Outcome, Oxidative stress, Heart Valve Prosthesis, Biological heart valves, Protein nitration
Abstract: International audience; The cause of structural valve deterioration (SVD) is unclear. Therefore, we investigated oxidative stress markers in sera from patients with bioprosthetic heart valves (BHVs) and their association with SVD. Blood samples were taken from SVD (Phase A) and BHV patients during the first 24 (Phase B1) and >48 months (Phase B2) after BHV implantation to assess total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrotyrosine (NT). The results show that MDA levels increased significantly 1 month after surgery in all groups but were higher at 6 months only in incipient SVD patients. NT levels increased gradually for the first 24 months after implantation in the BHV group. Patients with transcatheter aortic valve implantation (TAVI) showed even higher levels of stress markers. After >48 months, MDA and NT continued to increase in BHV patients with a further elevation after 60–72 months; however, these levels were significantly lower in the incipient and established SVD groups. In conclusion, oxidative stress may play a significant role in SVD, increasing early after BHV implantation, especially in TAVI cases, and also after 48 months’ follow-up, but decreasing when SVD develops. Oxidative stress potentially represents a target of therapeutic intervention and a biomarker of BHV dysfunction.
Published: 2022
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

7,170 results on '"Centre Hospitalier Universitaire de Nantes"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources