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1. Interruption or Discontinuation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukaemia: A Retrospective Cohort Study (SPARKLE) in Belgium

Author: Hematology Department - University Hospitals Leuven, Leuven, Devos, Timothy, Verhoef, Gregor, Steel, Eva, Mazure, Dominiek, Lewalle, Philippe, Bron, Dominique, Berneman, Zwi, Benghiat, Fleur Samantha, Mineur, Philippe, Theunissen, Koen, Zachée, Pierre, Doyen, Chantal, Put, Natalie, Lejeune, Marie, Van Eygen, Koen, Havelange, Violaine, Reusens, Michael, Pluymers, Wim, Peeters, Karen, Hematology Department - University Hospitals Leuven, Leuven, Devos, Timothy, Verhoef, Gregor, Steel, Eva, Mazure, Dominiek, Lewalle, Philippe, Bron, Dominique, Berneman, Zwi, Benghiat, Fleur Samantha, Mineur, Philippe, Theunissen, Koen, Zachée, Pierre, Doyen, Chantal, Put, Natalie, Lejeune, Marie, Van Eygen, Koen, Havelange, Violaine, Reusens, Michael, Pluymers, Wim, and Peeters, Karen
Abstract: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with chronic myeloid leukaemia (CML). Methods: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context) between May 2013 and May 2016. Data collection took place between October 2016 and February 2017. Results: All 60 participants (69 interruptions/discontinuations) had chronic-phase CML and 75% had at least a major molecular response (≥MMR) at interruption/discontinuation. Most interruptions/discontinuations occurred while on imatinib (36/69; 49%) and dasatinib (20/69; 29%). Most interruptions/discontinuations occurred due to side effects/intolerance (46/69; 67%); other reasons included a wish to conceive (6/69; 9%) and attempts to achieve treatment-free remission (TFR) (6/69; 9%). Interruptions due to side effects occurred later for imatinib- or dasatinib-treated patients than for those on nilotinib or ponatinib. Treatment was re-initiated in 62% (43/69) of cases. Most interruptions caused by side effects/intolerance were followed by treatment changes. All 4 patients with ≥MR 4.5 at interruption/discontinuation and ≥11-month follow-up who had not restarted treatment maintained the response. Conclusion: Although TKIs are used for long-term CML treatment, physicians sometimes recommend interruptions/discontinuations. In this study, interruptions/discontinuations were mainly caused by side effects or intolerance, rather than TFR attempts.
Published: 2019

2. Bacteraemia caused by Leptotrichia trevisanii in a neutropenic patient.

Author: GZA Sint-Augustinus, Wilrijk - Department of Microbiology, GZA Sint-Augustinus, Wilrijk - Department of Hematology, UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, University Hospitals Leuven, Leuven - Department of Microbiology, UCL - (SLuc) Service de microbiologie, Cooreman, S., Schuermans, C., Van Schaeren, J., Olive, Nathalie, Wauters, Georges, Verhaegen, J., Jeurissen, A., GZA Sint-Augustinus, Wilrijk - Department of Microbiology, GZA Sint-Augustinus, Wilrijk - Department of Hematology, UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, University Hospitals Leuven, Leuven - Department of Microbiology, UCL - (SLuc) Service de microbiologie, Cooreman, S., Schuermans, C., Van Schaeren, J., Olive, Nathalie, Wauters, Georges, Verhaegen, J., and Jeurissen, A.
Abstract: We describe an episode of Leptotrichia trevisanii bacteraemia in a neutropenic hemato-oncology patient receiving chemotherapy for Refractory Anemia with Excess Blasts–2 (RAEB-2). Although Leptotrichia spp. colonize the oral cavity and genitourinary tract, serious episodes of bacteraemia might occur in immunocompromised patients, particularly in those with severe neutropenia. Therefore, microbiologists should consider the possibility of Leptotrichia spp. septicemia in patients with blood cultures positive for gram negative bacilli, when routine microbiology tests fail to reveal a correct identification of the organism.
Published: 2011

3. Proposal for a rational classification of neck dissections

Author: Department of Otolaryngology???Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy ; Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy, Division of Otolaryngology???Head and Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, Head and Neck Service, Memorial Sloan???Kettering Cancer Center, New York, New York, Department of Otorhinolaryngology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, Departments of Surgery and Otolaryngology???Head and Neck Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, Department of Otolaryngology???Head and Neck Surgery, King Hussein Medical Center, Royal Medical Services, Amman, Jordan, Division of Otolaryngology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, Department of Otolaryngology???Head and Neck Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, Department of Otolaryngology???Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Department of Pathology, Allegiance Health, Jackson, Michigan, Department of Otorhinolaryngology???Head and Neck Surgery, Kantonsspital, St. Gallen, Switzerland, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, Department of Otorhinolaryngology???Head and Neck Surgery, Nottingham University Hospitals, Queens Medical Centre Campus, Nottingham, United Kingdom, Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain ; Instituto Universitario de Oncolog??a del Principado de Asturias, Oviedo, Spain, Department of Otolaryngology???Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands, Department of Otolaryngology???Head and Neck Surgery, Uludag University School of Medicine, Bursa, Turkey, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, Mississippi, Department of Otolaryngology???Head and Neck Surgery, Institut Gustave Roussy, Villejuif Cedex, France ; Laboratoire de Phon??tique et de Phonologie, Sorbonne Nouvelle, Paris, France, Department of Medicine, Division of Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, Department of Head and Neck Surgery, Head and Neck Oncology Program, St Luc University Hospital and Cancer Center, Brussels, Belgium, Head and Neck Surgery and Oncology Unit, A.R.M. Center for Advanced Otolaryngology???Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel, Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Department of Surgery, Division of Metabolic, Endocrine and Minimally Invasive Surgery, Mount Sinai School of Medicine, New York, New York, Department of Surgery, Universidad de La Sabana???Fundacion Abood Shaio, Bogota, Colombia, Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, Department of Otorhinolaryngology???Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium, Department of Otolaryngology???Head and Neck Surgery, Philipp University, Marburg, Germany, Department of Otolaryngology???Head and Neck Surgery, Holy Cross Cancer Centre, Kielce, Poland, Oral Pathology, University of Liverpool Dental Hospital, Liverpool, United Kingdom, Department of Otorhinolaryngology???Head and Neck Surgery, University Hospital, Berne, Switzerland, Department of Otorhinolaryngology???Head and Neck Surgery, 1st Faculty of Medicine, Faculty Hospital Motol, Charles University, Prague, Czech Republic, Department of Otorhinolaryngology???Head and Neck Surgery, Karl Hansen Medical Center, Bad Lippspringe, Germany, Department of Otolaryngology???Head and Neck Surgery, The Mount Sinai Medical Center, New York, New York, Head and Neck Service, The Chaim Sheba Medical Center, Tel Hashomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel, Department of Otolaryngology and Communicative Disorders, Cleveland Clinic Head and Neck Institute, Cleveland, Ohio, Department of Otorhinolaryngology, University Hospital A Coru??a, A Coru??a, Spain, Department of Otolaryngology???Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway, Department Otorhinolaryngology???Head and Neck Surgery, Centro de Tratamento e Pesquisa Hospital do Cancer A.C. Camargo, S??o Paulo, Brazil, Department of Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, Alabama, Department of Otolaryngology???Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan, Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy, Ferlito, Alfio, Robbins, K. Thomas, Shah, Jatin P., Medina, Jesus E., Silver, Carl E., Al-Tamimi, Shawkat, Fagan, Johannes J., Paleri, Vinidh, Takes, Robert P., Bradford, Carol R., Devaney, Kenneth O., Stoeckli, Sandro J., Weber, Randal S., Bradley, Patrick J., Su??rez, Carlos, Leemans, C. Ren??, Coskun, H. Hakan, Pitman, Karen T., Shaha, Ashok R., de Bree, Remco, Hartl, Dana M., Haigentz, Missak, Rodrigo, Juan P., Hamoir, Marc, Khafif, Avi, Langendijk, Johannes A., Owen, Randall P., Sanabria, Alvaro, Strojan, Primoz, Vander Poorten, Vincent, Werner, Jochen A., Bien, Stanis??aw, Woolgar, Julia A., Zb??ren, Peter, Betka, Jan, Folz, Benedikt J., Genden, Eric M., Talmi, Yoav P., Strome, Marshall, Gonz??lez Botas, Jes??s Herranz, Olofsson, Jan, Kowalski, Luiz P., Holmes, Jon D., Hisa, Yasuo, Rinaldo, Alessandra, Department of Otolaryngology???Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy ; Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy, Division of Otolaryngology???Head and Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, Head and Neck Service, Memorial Sloan???Kettering Cancer Center, New York, New York, Department of Otorhinolaryngology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, Departments of Surgery and Otolaryngology???Head and Neck Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, Department of Otolaryngology???Head and Neck Surgery, King Hussein Medical Center, Royal Medical Services, Amman, Jordan, Division of Otolaryngology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, Department of Otolaryngology???Head and Neck Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, Department of Otolaryngology???Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Department of Pathology, Allegiance Health, Jackson, Michigan, Department of Otorhinolaryngology???Head and Neck Surgery, Kantonsspital, St. Gallen, Switzerland, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, Department of Otorhinolaryngology???Head and Neck Surgery, Nottingham University Hospitals, Queens Medical Centre Campus, Nottingham, United Kingdom, Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain ; Instituto Universitario de Oncolog??a del Principado de Asturias, Oviedo, Spain, Department of Otolaryngology???Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands, Department of Otolaryngology???Head and Neck Surgery, Uludag University School of Medicine, Bursa, Turkey, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, Mississippi, Department of Otolaryngology???Head and Neck Surgery, Institut Gustave Roussy, Villejuif Cedex, France ; Laboratoire de Phon??tique et de Phonologie, Sorbonne Nouvelle, Paris, France, Department of Medicine, Division of Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, Department of Head and Neck Surgery, Head and Neck Oncology Program, St Luc University Hospital and Cancer Center, Brussels, Belgium, Head and Neck Surgery and Oncology Unit, A.R.M. Center for Advanced Otolaryngology???Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel, Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Department of Surgery, Division of Metabolic, Endocrine and Minimally Invasive Surgery, Mount Sinai School of Medicine, New York, New York, Department of Surgery, Universidad de La Sabana???Fundacion Abood Shaio, Bogota, Colombia, Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, Department of Otorhinolaryngology???Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium, Department of Otolaryngology???Head and Neck Surgery, Philipp University, Marburg, Germany, Department of Otolaryngology???Head and Neck Surgery, Holy Cross Cancer Centre, Kielce, Poland, Oral Pathology, University of Liverpool Dental Hospital, Liverpool, United Kingdom, Department of Otorhinolaryngology???Head and Neck Surgery, University Hospital, Berne, Switzerland, Department of Otorhinolaryngology???Head and Neck Surgery, 1st Faculty of Medicine, Faculty Hospital Motol, Charles University, Prague, Czech Republic, Department of Otorhinolaryngology???Head and Neck Surgery, Karl Hansen Medical Center, Bad Lippspringe, Germany, Department of Otolaryngology???Head and Neck Surgery, The Mount Sinai Medical Center, New York, New York, Head and Neck Service, The Chaim Sheba Medical Center, Tel Hashomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel, Department of Otolaryngology and Communicative Disorders, Cleveland Clinic Head and Neck Institute, Cleveland, Ohio, Department of Otorhinolaryngology, University Hospital A Coru??a, A Coru??a, Spain, Department of Otolaryngology???Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway, Department Otorhinolaryngology???Head and Neck Surgery, Centro de Tratamento e Pesquisa Hospital do Cancer A.C. Camargo, S??o Paulo, Brazil, Department of Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, Alabama, Department of Otolaryngology???Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan, Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy, Ferlito, Alfio, Robbins, K. Thomas, Shah, Jatin P., Medina, Jesus E., Silver, Carl E., Al-Tamimi, Shawkat, Fagan, Johannes J., Paleri, Vinidh, Takes, Robert P., Bradford, Carol R., Devaney, Kenneth O., Stoeckli, Sandro J., Weber, Randal S., Bradley, Patrick J., Su??rez, Carlos, Leemans, C. Ren??, Coskun, H. Hakan, Pitman, Karen T., Shaha, Ashok R., de Bree, Remco, Hartl, Dana M., Haigentz, Missak, Rodrigo, Juan P., Hamoir, Marc, Khafif, Avi, Langendijk, Johannes A., Owen, Randall P., Sanabria, Alvaro, Strojan, Primoz, Vander Poorten, Vincent, Werner, Jochen A., Bien, Stanis??aw, Woolgar, Julia A., Zb??ren, Peter, Betka, Jan, Folz, Benedikt J., Genden, Eric M., Talmi, Yoav P., Strome, Marshall, Gonz??lez Botas, Jes??s Herranz, Olofsson, Jan, Kowalski, Luiz P., Holmes, Jon D., Hisa, Yasuo, and Rinaldo, Alessandra
Abstract: No abstract.
Published: 2011

4. Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology

Author: Elisabet Van Loon, Baptiste Lamarthée, Henriette de Loor, Amaryllis H. Van Craenenbroeck, Sophie Brouard, Richard Danger, Magali Giral, Jasper Callemeyn, Claire Tinel, Álvaro Cortés Calabuig, Priyanka Koshy, Ben Sprangers, Dirk Kuypers, Wilfried Gwinner, Dany Anglicheau, Pierre Marquet, Maarten Naesens, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], 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), 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), Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t) (U1064 Inserm - CR2TI), 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 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)-Nantes Université (Nantes Univ), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, Hannover Medical School [Hannover] (MHH), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), 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), and KERANDEL-DION, Céline
Subjects: Graft Rejection, Biopsy, Allografts, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, Antibodies, BK virus, immune cells, kidney transplantation rejection, Nephrology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], gene expression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Transcriptome, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Immunosuppressive Agents
Abstract: Kidney transplant injury processes are associated with molecular changes in kidney tissue, primarily related to immune cell activation and infiltration. How these processes are reflected in the circulating immune cells, whose activation is targeted by strong immunosuppressants, is poorly understood. To study this, we analyzed the molecular alterations in 384 peripheral blood samples from four European transplant centers, taken at the time of a kidney allograft biopsy, selected for their phenotype, using RNA-sequencing. In peripheral blood, differentially expressed genes in 136 rejection and 248 no rejection samples demonstrated upregulation of glucocorticoid receptor and nucleotide oligomerization domain-like receptor signaling pathways. Pathways enriched in antibody-mediated rejection (ABMR) were strongly immune-specific, whereas pathways enriched in T cell-mediated rejection were less immune related. In polyomavirus infection, upregulation of mitochondrial dysfunction and interferon signaling pathways was seen. Next, we integrated the blood results with transcriptomics of 224 kidney allograft biopsies which showed consistently upregulated genes per phenotype in both blood and biopsy. In single-cell RNASeq (scRNASeq) analysis of seven kidney allograft biopsies, the consistently overexpressed genes in ABMR were mostly expressed by infiltrating leukocytes in the allograft. Similarly, in peripheral blood scRNASeq analysis, these genes were overexpressed in ABMR in immune cell subtypes. Furthermore, overexpression of these genes in ABMR was confirmed in independent cohorts in blood and biopsy. Thus, our results highlight the immune activation pathways in peripheral blood leukocytes at the time of kidney allograft pathology, despite the use of current strong immunosuppressants, and provide a framework for future therapeutic interventions. ispartof: KIDNEY INTERNATIONAL vol:102 issue:1 pages:183-195 ispartof: location:United States status: published
Published: 2022

5. T1w/FLAIR ratio standardization as a myelin marker in MS patients

Author: Cappelle, Sarah, Pareto Onghena, Deborah, Sunaert, Stefan, Smets, Ide, Laenen, Annouschka, Dubois, Benedicte, Demaerel, Philippe, Neurology, Cappelle, S., Pareto, D., Sunaert, S., Smets , I, LAENEN, Annouschka, Dubois, B., Demaerel, Ph, Institut Català de la Salut, [Cappelle S] Department of Radiology, University Hospitals Leuven, Leuven, Belgium. [Pareto D] Institut de Diagnòstic per la Imatge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sunaert S, Demaerel P] Department of Radiology, University Hospitals Leuven, Leuven, Belgium. Department of Imaging & Pathology, Translational MRI, KU Leuven, Leuven, Belgium. [Smets I] Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium. Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. [Laenen A] Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven and Hasselt University, Leuven, Belgium. [Dubois B] Laboratory for Neuroimmunology, KU Leuven, Leuven, Belgium. Department of Neurology, University Hospitals Leuven, Leuven, Belgium, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Integrity, Cognitive Neuroscience, Neuroimaging, T1w/T2w ratio, Multiple sclerosis, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], WATER, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Radiology, Nuclear Medicine and imaging, Esclerosi múltiple - Imatgeria per ressonància magnètica, Science & Technology, CORTICAL PATHOLOGY, Image calibration, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], MULTIPLE-SCLEROSIS, Mielina, tejidos::tejido nervioso::vaina de mielina [ANATOMÍA], T1w/FLAIR ratio, Neurology, Tissues::Nerve Tissue::Myelin Sheath [ANATOMY], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Neurosciences & Neurology, Neurology (clinical), Life Sciences & Biomedicine, WHITE-MATTER, MRI
Abstract: Image calibration; Integrity; Multiple sclerosis Calibración de imagen; Integridad; Esclerosis múltiple Calibració d'imatge; Integritat; Esclerosi múltiple Introduction Calculation of a T1w/T2w ratio was introduced as a proxy for myelin integrity in the brain of multiple sclerosis (MS) patients. Since nowadays 3D FLAIR is commonly used for lesion detection instead of T2w images, we introduce a T1w/FLAIR ratio as an alternative for the T1w/T2w ratio. Objectives Bias and intensity variation are widely present between different scanners, between subjects and within subjects over time in T1w, T2w and FLAIR images. We present a standardized method for calculating a histogram calibrated T1w/FLAIR ratio to reduce bias and intensity variation in MR sequences from different scanners and at different time-points. Material and methods 207 Relapsing Remitting MS patients were scanned on 4 different 3 T scanners with a protocol including 3D T1w, 2D T2w and 3D FLAIR images. After bias correction, T1w/FLAIR ratio maps and T1w/T2w ratio maps were calculated in 4 different ways: without calibration, with linear histogram calibration as described by Ganzetti et al. (2014), and by using 2 methods of non-linear histogram calibration. The first nonlinear calibration uses a template of extra-cerebral tissue and cerebrospinal fluid (CSF) brought from Montreal Neurological Institute (MNI) space to subject space; for the second nonlinear method we used an extra-cerebral tissue and CSF template of our own subjects. Additionally, we segmented several brain structures such as Normal Appearing White Matter (NAWM), Normal Appearing Grey Matter (NAGM), corpus callosum, thalami and MS lesions using Freesurfer and Samseg. Results The coefficient of variation of T1w/FLAIR ratio in NAWM for the no calibrated, linear, and 2 nonlinear calibration methods were respectively 24, 19.1, 9.5, 13.8. The nonlinear methods of calibration showed the best results for calculating the T1w/FLAIR ratio with a smaller dispersion of the data and a smaller overlap of T1w/FLAIR ratio in the different segmented brain structures. T1w/T2w and T1w/FLAIR ratios showed a wider range of values compared to MTR values. Conclusions Calibration of T1w/T2w and T1w/FLAIR ratio maps is imperative to account for the sources of variation described above. The nonlinear calibration methods showed the best reduction of between-subject and within-subject variability. The T1w/T2w and T1w/FLAIR ratio seem to be more sensitive to smaller changes in tissue integrity than MTR. Future work is needed to determine the exact substrate of T1w/FLAIR ratio and to obtain correlations with clinical outcome.
Published: 2022

6. Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial

Author: Schoisswohl, Stefan, Langguth, Berthold, Schecklmann, Martin, Bernal-Robledano, Alberto, Boecking, Benjamin, Cederroth, Christopher R., Chalanouli, Dimitra, Cima, Rilana, Denys, Sam, Dettling-Papargyris, Juliane, Escalera-Balsera, Alba, Espinosa-Sanchez, Juan Manuel, Gallego-Martinez, Alvaro, Giannopoulou, Efi, Hidalgo-Lopez, Leyre, Hummel, Michael, Kikidis, Dimitris, Koller, Michael, Lopez-Escamez, Jose A., Marcrum, Steven C., Markatos, Nikolaos, Martin-Lagos, Juan, Martinez-Martinez, Maria, Martinez-Martinez, Marta, Ferron, Maria Mata, Mazurek, Birgit, Mueller-Locatelli, Nicolas, Neff, Patrick, Oppel, Kevin, Perez-Carpena, Patricia, Robles-Bolivar, Paula, Rose, Matthias, Schiele, Tabea, Schiller, Axel, Simoes, Jorge, Stark, Sabine, Staudinger, Susanne, Stege, Alexandra, Verhaert, Nicolas, Schlee, Winfried, [Schoisswohl,S, Langguth,B, Schecklmann,M, Neff,P, Schiller,A, Simoes,J, Staudinger,S, Schlee,W] Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany. [Bernal-Robledano,A, Espinosa-Sanchez,JM, Lopez-Escamez,JA, Martinez-Martinez,M, Mata Ferron,M, Perez-Carpena,P] Department of Otolaryngology, Instituto de Investigacion Biosanitaria Ibs.GRANADA, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Boecking,B, Mazurek,B, Schiele,T, Stark,S] Tinnitus Center, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin und Humboldt Universität Berlin, Berlin, Germany. [Cederroth,CR] Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. [Chalanouli,D, Giannopoulou,E] EXCELYA Hungary Kft., Budakalász, Hungary. [Cima,R] Department of Health Psychology, Katholieke Universiteit Leuven, Leuven, Belgium. [Denys,S, Verhaert,N] Department of Neurosciences, Research group Experimental Oto-Rhino-Laryngology, University of Leuven, Leuven, Belgium. [Denys,S, Verhaert,N] Department of Otorhinolaryngology - Head and Neck surgery, University Hospitals Leuven, Leuven, Belgium. [Denys,S, Verhaert,N] Multidisciplinary University Center for Speech-Language Pathology and Audiology, University Hospitals Leuven, Leuven, Belgium. [Dettling-Papargyris,J, Oppel,K] Terzo-Institute for Applied Hearing Research, ISMA, Sonneberg, Germany. [Escalera-Balsera,A, Gallego-Martinez,A, Perez-Carpena,P, Robles-Bolivar,P] Otology & Neurotology Group CTS 495, Department of Genomic Medicine, GENYO, Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain. [Hidalgo-Lopez,L] Department of Mental Health, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Hummel,M, Stege,A] Central Biobank Charité, Charité- Universitätsmedizin Berlin, corporate member of Freie Universität Berlin und Humboldt Universität Berlin, Berlin, Germany. [Kikidis,D, Markatos,N] Department of Otolaryngology, Head and Neck Surgery, National and Kapodistrian University of Athens, Hippocrateion General Hospital, Athens, Greece. [Koller,M] Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany. [Lopez-Escamez,JA] Department of Surgery, Division of Otolaryngology, Universidad de Granada, Granada, Spain. [Marcrum,SC] Department of Otolaryngology, University Hospital Regensburg, Regensburg, Germany. [Martin-Lagos,J, Mueller-Locatelli,N] Department of Otolaryngology, Instituto de Investigacion Biosanitaria ibs. GRANADA, Hospital Universitario Clinico San Cecilio, Granada, Spain. [Neff,P] Center for Cognitive Neuroscience and Department of Psychology, University of Salzburg, Salzburg, Austria. [Rose,M] epartment of Psychosomatic and Psychotherapy, Charité- Universitätsmedizin Berlin, corporate member of Freie Universität Berlin und Humboldt Universität Berlin, Berlin, Germany., and The UNITI project has received funding from the European Union’s Horizon2020 Research and Innovation Program (grant agreement number 848261). Open Access funding enabled and organized by Projekt DEAL.
Subjects: Counseling, Medicine (General), Terapéutica, 610 Medizin, Medicine (miscellaneous), Sound therapy, Research & Experimental Medicine, THERAPY, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, Consejo, Tinnitus, 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings], QUALITY-OF-LIFE, Multicenter Studies as Topic, ANXIETY, Pharmacology (medical), Multi-center, 030223 otorhinolaryngology, Terapia de sonidos, Randomized Controlled Trials as Topic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic [Medical Subject Headings], ddc:610, SOUND, Audífonos, PHQ-9, Psychiatry and Psychology::Behavioral Disciplines and Activities::Psychotherapy::Behavior Therapy::Cognitive Therapy [Medical Subject Headings], 3. Good health, Terapia cognitivo-conductual, Medicine, Research & Experimental, Tinnitus, Treatment, Hearing aids, Cognitive behavioral therapy, Sound therapy, Structured counseling, Multi-center, RCT, Structured counseling, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Sensory Aids::Hearing Aids [Medical Subject Headings], Life Sciences & Biomedicine, Psychiatry and Psychology::Psychological Phenomena and Processes::Psychology, Applied::Counseling [Medical Subject Headings], RCT, Hearing aids, DISORDERS, 03 medical and health sciences, R5-920, MANAGEMENT, otorhinolaryngologic diseases, Humans, Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Hearing Disorders::Tinnitus [Medical Subject Headings], COMBINATION, Science & Technology, HEARING-LOSS, Acúfeno, Cognitive behavioral therapy, Treatment, SEVERITY, Ensayos clínicos controlados no aleatorios como asunto, 030217 neurology & neurosurgery
Abstract: The UNITI project has received funding from the European Union's Horizon 2020 Research and Innovation Program (grant agreement number 848261)., Background: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). Methods/study design: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. Discussion: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus., European Union's Horizon 2020 Research and Innovation Program 848261
Published: 2021

7. Transcriptional changes in kidney allografts with histology of antibody-mediated rejection without anti-HLA donor-specific antibodies

Author: Vannary Meas-Yedid, Leentje Van Lommel, Olivier Thaunat, Wilfried Gwinner, Marie Essig, Henriette de Loor, Evelyne Lerut, Frans Schuit, Jasper Callemeyn, Alice Koenig, Dirk Kuypers, Maarten Naesens, Ben Sprangers, Pierre Marquet, J. Chang, Jean-Christophe Olivo-Marin, Lieven Thorrez, Philip F. Halloran, Dany Anglicheau, I. Arijs, Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, University Hospitals Leuven [Leuven], Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse d'Images Quantitative, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Analyse d'images biologiques - Biological Image Analysis (BIA), Gene Expression Unit, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hannover Medical School [Hannover] (MHH), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Graft Rejection, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Transcription, Genetic, [SDV]Life Sciences [q-bio], Human leukocyte antigen, 030230 surgery, Kidney, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Isoantibodies, Clinical Research, Biopsy, medicine, Humans, Transplantation, Homologous, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Aged, biology, medicine.diagnostic_test, business.industry, Graft Survival, Hazard ratio, Histology, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Concomitant, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, business
Abstract: Background Circulating donor-specific anti-HLA antibodies (HLA-DSAs) are often absent in serum of kidney allograft recipients whose biopsy specimens demonstrate histology of antibody-mediated rejection (ABMR). It is unclear whether cases involving ABMR histology without detectable HLA-DSAs represent a distinct clinical and molecular phenotype. Methods In this multicenter cohort study, we integrated allograft microarray analysis with extensive clinical and histologic phenotyping from 224 kidney transplant recipients between 2011 and 2017. We used the term ABMR histology for biopsy specimens that fulfill the first two Banff 2017 criteria for ABMR, irrespective of HLA-DSA status. Results Of 224 biopsy specimens, 56 had ABMR histology; 26 of these (46.4%) lacked detectable serum HLA-DSAs. Biopsy specimens with ABMR histology showed overexpression of transcripts mostly related to IFNγ-induced pathways and activation of natural killer cells and endothelial cells. HLA-DSA-positive and HLA-DSA-negative biopsy specimens with ABMR histology displayed similar upregulation of pathways and enrichment of infiltrating leukocytes. Transcriptional heterogeneity observed in biopsy specimens with ABMR histology was not associated with HLA-DSA status but was caused by concomitant T cell-mediated rejection. Compared with cases lacking ABMR histology, those with ABMR histology and HLA-DSA had higher allograft failure risk (hazard ratio [HR], 7.24; 95% confidence interval [95% CI], 3.04 to 17.20) than cases without HLA-DSA (HR, 2.33; 95% CI, 0.85 to 6.33), despite the absence of transcriptional differences. Conclusions ABMR histology corresponds to a robust intragraft transcriptional signature, irrespective of HLA-DSA status. Outcome after ABMR histology is not solely determined by the histomolecular presentation but is predicted by the underlying etiologic factor. It is important to consider this heterogeneity in further research and in treatment decisions for patients with ABMR histology.
Published: 2020

8. Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air ® App

Author: Bédard, Annabelle, Antó, Josep, Fonseca, Joao, Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Cardona, Victoria, Cruz, Alvaro, Fokkens, Wytske, Garcia-Aymerich, Judith, Hellings, Peter, Ivancevich, Juan, Klimek, Ludger, Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Désirée, Melen, Erik, Monti, Ricardo, Mösges, Ralf, Mullol, Joaquim, Papadopoulos, Nikos, Pham-Thi, Nhan, Samolinski, Boleslaw, V Tomazic, Peter, Toppila-Salmi, Sanna, Ventura, Maria Teresa, Yorgancioglu, Arzu, Bousquet, Jean, Pfaar, Oliver, Basagana, Xavier, Bosnic‐Anticevich, Sinthia, Pham‐Thi, Nhân, Hellings, PW, Aberer, W., Agache, I., Akdis, Ca, Akdis, M., Aliberti, MR, Almeida, R., Amat, F., Angles, R, Annesi‐Maesano, I, Ansotegui, IJ, Anto, JM, Arnavielle, S, Asayag, E, Asarnoj, A, Arshad, H, Avolio, F, Bacci, E, Baiardini, I, Barbara, C, Barbagallo, M., Baroni, I, Barreto, BA, Basagaña, X., Bateman, ED, Bedolla‐Barajas, M, Bewick, M., Beghé, B., Bel, EH, Bergmann, KC, Bennoor, KS, Benson, M, Bertorello, L, Białoszewski, AZ, Bieber, T., Bialek, S, Bindslev‐Jensen, Carsten, Bjermer, L., Blain, H., Blasi, F., Blua, A, Bochenska Marciniak, M, Bogus‐Buczynska, I, Boner, AL, Bonini, M., Bonini, S., Bosnic‐Anticevich, CS, Bosse, I., Bouchard, J., Boulet, LP, Bourret, R., Bousquet, Pj, Braido, F, Briedis, V, Brightling, CE, Brozek, J, Bucca, C, Buhl, R, Buonaiuto, R, Panaitescu, C, Burguete Cabañas, MT, Burte, E., Bush, A, Caballero‐Fonseca, F, Caillaud, D., Caimmi, D., Calderon, MA, Camargos, PAM, Camuzat, T., Canfora, G, Canonica, Gw, Carlsen, KH, Carreiro‐Martins, P, Carriazo, AM, Carr, W, Cartier, C., Casale, T., Castellano, G, Cecchi, L, Cepeda, AM, Chavannes, NH, Chen, Y., Chiron, R., Chivato, T, Chkhartishvili, E, Chuchalin, AG, Chung, KF, Ciaravolo, MM, Ciceran, A, Cingi, C, Ciprandi, G, Carvalho Coehlo, AC, Colas, L, Colgan, E, Coll, J, Conforti, D, Constantinidis, J, de Sousa, J Correia, Cortés‐Grimaldo, RM, Corti, F, Costa, E, Costa‐Dominguez, MC, Courbis, AL, Cox, L, Crescenzo, M, Cruz, AA, Custovic, A., Czarlewski, W., Dahlen, Se, D’Amato, G, Dario, C, Da Silva, J., Dauvilliers, Y., Darsow, U, De Blay, F., De Carlo, G, Dedeu, T, de Fátima Emerson, M, De Feo, G., De Vries, G, De Martino, B, Motta Rubini, NP, Deleanu, D, Denburg, JA, devillier, P., Di Capua Ercolano, S, Di Carluccio, N, Didier, A., Dokic, D, Dominguez‐Silva, MG, Douagui, H, Dray, G., Dubakiene, R, Durham, Sr, Du Toit, G, Dykewicz, MS, El‐Gamal, Y, Eklund, P, Eller, E, Emuzyte, R., Farrell, J, Farsi, A, de Mello, J Ferreira, Ferrero, J, Fink‐Wagner, A, Fiocchi, A, Fokkens, WJ, Fonseca, JA, Fontaine, Jf, Forti, S, Fuentes‐Perez, JM, Gálvez‐Romero, JL, Gamkrelidze, A, Garcia‐Aymerich, Judith, García‐Cobas, CY, Garcia‐Cruz, MH, Gemicioğlu, B, Genova, S, Christoff, G, Gereda, JE, Van Wijk, R Gerth, Gomez, RM, Gómez‐Vera, J, González Diaz, S, Gotua, M., Grisle, I, Guidacci, M, Guldemond, NA, Gutter, Z, Guzmán, MA, Haahtela, T., Hajjam, J, Hernández, L, Hourihane, JO’B, Huerta‐Villalobos, YR, Humbert, M., Iaccarino, G., Illario, M, Ispayeva, Z, Ivancevich, JC, Jares, EJ, Jassem, E, Johnston, Sl, Joos, G, Jung, KS, Just, J., Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, AF, Karjalainen, J, Kardas, P, Keil, T, Keith, PK, Khaitov, M, Khaltaev, N, Kleine‐Tebbe, J, Kowalski, Ml, Kuitunen, M, Kull, I., Kupczyk, M, Krzych‐Fałta, E, Lacwik, P, Larenas‐Linnemann, Désirée, Laune, D., Lauri, D, Lavrut, J, Le, LTT, Lessa, M, Levato, G, Li, J., Lieberman, P, Lipiec, A, Lipworth, B, Lodrup Carlsen, KC, Louis, R, Lourenço, O, Luna‐Pech, JA, Magnan, A., Mahboub, B, Maier, D., Mair, A, Majer, I, Malva, J, Mandajieva, E, Manning, P, De Manuel Keenoy, E, Marshall, GD, Masjedi, MR, Maspero, JF, Mathieu‐Dupas, E, Matta Campos, JJ, Matos, AL, Maurer, M, Mavale‐Manuel, S, Mayora, O, Meco, C, Medina‐Avalos, MA, Melo‐Gomes, E, Meltzer, EO, Menditto, E., Miculinic, N, Mihaltan, F., Milenkovic, B, Moda, G, Mogica‐Martinez, MD, Mohammad, Y, Momas, I., Montefort, S, Mora Bogado, D, Morais‐Almeida, M, Morato‐Castro, FF, Mota‐Pinto, A, Moura Santo, P, Münter, L, Muraro, A, Murray, R, Naclerio, R., Nadif, R., Nalin, M, Napoli, L, Namazova‐Baranova, L, Neffen, H, Niedeberger, V, Nekam, K, Neou, A, Nieto, A, Nogueira‐Silva, L, Nogues, M., Novellino, E, Nyembue, TD, O’Hehir, RE, Odzhakova, C, Ohta, K., Okamoto, Y., Okubo, K, Onorato, GL, Ortega Cisneros, M, Ouédraogo, S., Pali‐Schöll, I, Palkonen, S, Panzner, P, Papadopoulos, NG, Park, HS, Papi, A., Passalacqua, G, Paulino, E, Pawankar, R, Pedersen, S, Pépin, JL, Pereira, AM, Persico, M, PHILLIPS, J, Picard, R., Pigearias, B, Pin, I., Pitsios, C., Plavec, D, Pohl, W, Popov, TA, Portejoie, F., Potter, P, Pozzi, AC, Price, D, Prokopakis, EP, Puy, R, Pugin, B, Pulido Ross, RE, Przemecka, M, Rabe, KF, Raciborski, F, Rajabian‐Soderlund, R, Reitsma, S, Ribeirinho, I, Rimmer, J, Rivero‐Yeverino, D, Rizzo, JA, Rizzo, MC, Robalo‐Cordeiro, C, Rodenas, F, Rodo, X, Rodriguez Gonzalez, M, Rodriguez‐Mañas, L, Rolland, C, Rodrigues Valle, S, Roman Rodriguez, M., Romano, A, Rodriguez‐Zagal, E, Rolla, G, Roller‐Wirnsberger, RE, Romano, M, Rosado‐Pinto, J, Rosario, N., Rottem, M, Ryan, D, Sagara, H, Salimäki, J, Sanchez‐Borges, M, Sastre‐Dominguez, J, Scadding, GK, Schunemann, HJ, Scichilone, N, Schmid‐Grendelmeier, P, Sarquis Serpa, F, Shamai, S., Sheikh, A., Sierra, M, Simons, FER, Siroux, V., Sisul, JC, Skrindo, I, Solé, D, Somekh, D, Sondermann, M, Sooronbaev, T, Sova, M, Sorensen, M, Sorlini, M, Spranger, O, Stellato, C, Stelmach, R, Stukas, R, Sunyer, J., Strozek, J, Szylling, A, Tebyriçá, JN, Thibaudon, M., To, T., Todo‐Bom, A, Tomazic, PV, Toppila‐Salmi, Sanna, Trama, U, Triggiani, M, Suppli Ulrik, C, Urrutia‐Pereira, M, Valenta, R, Valero, A., Valiulis, A., Valovirta, E., van Eerd, M, Van Ganse, E., van Hage, M, Vandenplas, O, Ventura, MT, Vezzani, G, Vasankari, T, Vatrella, A., Verissimo, MT, Viart, F., Viegi, G., Vicheva, D, Vontetsianos, T, Wagenmann, M, Walker, S, Wallace, D, Wang, DY, Waserman, S., Werfel, T, Westman, M, Wickman, M., Williams, DM, Williams, S, Wilson, N, Wright, J, Wroczynski, P, Yakovliev, P, Yawn, BP, Yiallouros, PK, Yusuf, OM, Zar, HJ, Zhang, L., Zhong, N, Zernotti, ME, Zhanat, I, Zidarn, M, Zuberbier, T., Zubrinich, C, Zurkuhlen, A, Mercier, Jacques, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, KYomed INNOV, Ghent University Hospital, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Odense University Hospital [Odense, Denmark], Woolcock Institute of Medical Research [Sydney], The University of Sydney, Vall d'Hebron University Hospital [Barcelona], ProAR - FMB, Federal University of Bahia School of Medicine, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), University Hospitals Leuven [Leuven], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], Clínica de Alergia- Asma y Pediatría, Hospital Medica Sur, Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Medical University of Warsaw - Poland, Department of Pulmonology, Manisa Celal Bayar University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Aix Marseille Université (AMU), Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), iQ4U consultants Ltd, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Department of Respiratory Medicine and Allergy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, CHU Montpellier, Laboratoire National Henri Becquerel (LNHB), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Département d'instrumentation Numérique (DIN (CEA-LIST)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Région Languedoc-Roussillon-Midi-Pyrénées, University of South Florida [Tampa] (USF), Chinese academy of sciences Sanya, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Laboratoire de Génie Informatique et d'Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Paediatrics, UCB Pharma, Colombes, CHU Strasbourg, Università degli Studi di Salerno = University of Salerno (UNISA), Hôpital Foch [Suresnes], Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Informatique, Image, Intelligence Artificielle (I3A), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IMT - MINES ALES (IMT - MINES ALES), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Center for Turbulence Research [Stanford] (CTR), Stanford University, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biomax Informatics AG, 'Federico II' University of Naples Medical School, Pneumology Department, Marius Nasta Institute of Pneumology, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Johns Hopkins University School of Medicine [Baltimore], CARSAT-LR, Montpellier, Dept. of Electronic Engineering, Chubu University, Institute for Solid State Physics, The University of Tokyo (UTokyo), Respiratory Medicine, Laboratoire de physique et chimie des nano-objets (LPCNO), 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 de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, University of Cyprus [Nicosia] (UCY), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Computer Science [Haifa], University of Haifa [Haifa], University of Edinburgh, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Réseau National de Surveillance Aérobiologique (RNSA), CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, University of Turku, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-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), ASA (Advanced Solution Accelerator) (Data management : Développement Back-Office, hébergement…), 34830 Jacou, Consiglio nazionale delle ricerche, Instituto di fisiologia clinica, McMaster University [Hamilton, Ontario], Department of Molecular Medicine and Surgery, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), University Hospital of Cologne [Cologne], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ISGlobal, Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda Porto, Porto, Portugal, KYomed INNOV, Montpellier, France, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, MACVIA-France, Montpellier, France, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, Australia, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Salvador, Brazil, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, Euforea, Brussels, Belgium, Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania, Clinic of Chest diseases and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, Pasteur Institute, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Department of General ORL, H&NS, Medical University of Graz, Graz, Austria, Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, University Hospital, Montpellier, France, INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität, Marburg, Germany, Universidade do Porto, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur [Paris], University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli Studi di Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, University of Helsinki, Service d'Allergologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bedard, A., Anto, J. M., Fonseca, J. A., Arnavielhe, S., Bachert, C., Bedbrook, A., Bindslev-Jensen, C., Bosnic-Anticevich, S., Cardona, V., Cruz, A. A., Fokkens, W. J., Garcia-Aymerich, J., Hellings, P. W., Ivancevich, J. C., Klimek, L., Kuna, P., Kvedariene, V., Larenas-Linnemann, D., Melen, E., Monti, R., Mosges, R., Mullol, J., Papadopoulos, N. G., Pham-Thi, N., Samolinski, B., Tomazic, P. V., Toppila-Salmi, S., Ventura, M. T., Yorgancioglu, A., Bousquet, J., Pfaar, O., Basagana, X., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Bateman, E. D., Bedolla-Barajas, M., Bewick, M., Beghe, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Bialoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabanas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Constantinidis, J., Correia de Sousa, J., Cortes-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Czarlewski, W., Dahlen, S. E., D'Amato, G., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fatima Emerson, M., De Feo, G., De Vries, G., De Martino, B., Motta Rubini, N. P., Deleanu, D., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Galvez-Romero, J. L., Gamkrelidze, A., Garcia-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioglu, B., Genova, S., Christoff, G., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gomez-Vera, J., Gonzalez Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzman, M. A., Haahtela, T., Hajjam, J., Hernandez, L., Hourihane, J. O. '. B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kull, I., Kupczyk, M., Krzych-Falta, E., Lacwik, P., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenco, O., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Meco, C., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Munter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Scholl, I., Palkonen, S., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pepin, J. L., Pereira, A. M., Persico, M., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Manas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimaki, J., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Sarquis Serpa, F., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Sole, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyrica, J. N., Thibaudon, M., To, T., Todo-Bom, A., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hage, M., Vandenplas, O., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zhanat, I., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universidade do Porto [Porto], Kyomed, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Universitat Pompeu Fabra [Barcelona], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology [Graz, Austria], Medical University Graz, University of Zürich [Zürich] (UZH), National Institute for Nuclear Physics (INFN), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), University of South Florida (USF), University of Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey, Institut Mines-Télécom [Paris] (IMT), Center for Turbulence Research (CTR), Stanford University [Stanford], Service d'allergologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo, Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), RNSA, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bedard A., Anto J.M., Fonseca J.A., Arnavielhe S., Bachert C., Bedbrook A., Bindslev-Jensen C., Bosnic-Anticevich S., Cardona V., Cruz A.A., Fokkens W.J., Garcia-Aymerich J., Hellings P.W., Ivancevich J.C., Klimek L., Kuna P., Kvedariene V., Larenas-Linnemann D., Melen E., Monti R., Mosges R., Mullol J., Papadopoulos N.G., Pham-Thi N., Samolinski B., Tomazic P.V., Toppila-Salmi S., Ventura M.T., Yorgancioglu A., Bousquet J., Pfaar O., Basagana X., Aberer W., Agache I., Akdis C.A., Akdis M., Aliberti M.R., Almeida R., Amat F., Angles R., Annesi-Maesano I., Ansotegui I.J., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Bateman E.D., Bedolla-Barajas M., Bewick M., Beghe B., Bel E.H., Bergmann K.C., Bennoor K.S., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blain H., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bosse I., Bouchard J., Boulet L.P., Bourret R., Bousquet P.J., Braido F., Briedis V., Brightling C.E., Brozek J., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillaud D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Canonica G.W., Carlsen K.H., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Casale T., Castellano G., Cecchi L., Cepeda A.M., Chavannes N.H., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., Constantinidis J., Correia de Sousa J., Cortes-Grimaldo R.M., Corti F., Costa E., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Czarlewski W., Dahlen S.E., D'Amato G., Dario C., da Silva J., Dauvilliers Y., Darsow U., De Blay F., De Carlo G., Dedeu T., de Fatima Emerson M., De Feo G., De Vries G., De Martino B., Motta Rubini N.P., Deleanu D., Denburg J.A., Devillier P., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Dubakiene R., Durham S.R., Du Toit G., Dykewicz M.S., El-Gamal Y., Eklund P., Eller E., Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Fontaine J.F., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., Christoff G., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Guzman M.A., Haahtela T., Hajjam J., Hernandez L., Hourihane J.O.'.B., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Illario M., Ispayeva Z., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu A.F., Karjalainen J., Kardas P., Keil T., Keith P.K., Khaitov M., Khaltaev N., Kleine-Tebbe J., Kowalski M.L., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Laune D., Lauri D., Lavrut J., Le L.T.T., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Lourenco O., Luna-Pech J.A., Magnan A., Mahboub B., Maier D., Mair A., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Meco C., Medina-Avalos M.A., Melo-Gomes E., Meltzer E.O., Menditto E., Mercier J., Miculinic N., Mihaltan F., Milenkovic B., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Mora Bogado D., Morais-Almeida M., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Murray R., Naclerio R., Nadif R., Nalin M., Napoli L., Namazova-Baranova L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Novellino E., Nyembue T.D., O'Hehir R.E., Odzhakova C., Ohta K., Okamoto Y., Okubo K., Onorato G.L., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Palkonen S., Panzner P., Park H.S., Papi A., Passalacqua G., Paulino E., Pawankar R., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Plavec D., Pohl W., Popov T.A., Portejoie F., Potter P., Pozzi A.C., Price D., Prokopakis E.P., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Rajabian-Soderlund R., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rodriguez-Zagal E., Rolla G., Roller-Wirnsberger R.E., Romano M., Rosado-Pinto J., Rosario N., Rottem M., Ryan D., Sagara H., Salimaki J., Sanchez-Borges M., Sastre-Dominguez J., Scadding G.K., Schunemann H.J., Scichilone N., Schmid-Grendelmeier P., Sarquis Serpa F., Shamai S., Sheikh A., Sierra M., Simons F.E.R., Siroux V., Sisul J.C., Skrindo I., Sole D., Somekh D., Sondermann M., Sooronbaev T., Sova M., Sorensen M., Sorlini M., Spranger O., Stellato C., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., To T., Todo-Bom A., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., Valero A., Valiulis A., Valovirta E., van Eerd M., van Ganse E., van Hage M., Vandenplas O., Vezzani G., Vasankari T., Vatrella A., Verissimo M.T., Viart F., Viegi G., Vicheva D., Vontetsianos T., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Werfel T., Westman M., Wickman M., Williams D.M., Williams S., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zhang L., Zhong N., Zernotti M.E., Zhanat I., Zidarn M., Zuberbier T., Zubrinich C., and Zurkuhlen A.
Subjects: 0301 basic medicine, SYMPTOMS, Smart phone, Allergy, Escala visual analógica, INNOVATION, [SDV]Life Sciences [q-bio], Medical and Health Sciences, Correlation, visual analogue scale, 0302 clinical medicine, Quality of life, Visual analogue scale, QUALITY-OF-LIFE, Màscares, Immunology and Allergy, score, Nose, Rinitis, Rhinitis, PRODUCTIVITY COSTS, asthma, MASK, rhinitis, Score, Explained variation, Response Variability, Mobile Applications, ALLERGIC RHINITIS, rhiniti, medicine.anatomical_structure, TRIALS, Rinite, 1107 Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Smartphone, medicine.medical_specialty, MASK study group, Immunology, MACVIA-ARIA, 03 medical and health sciences, Allergic, medicine, Humans, TECHNOLOGY, IMMUNOTHERAPY, Asma, Asthma, business.industry, Rhinitis, Allergic, medicine.disease, RHINOCONJUNCTIVITIS, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2020

9. Mobile Technology in Allergic Rhinitis: Evolution in Management or Revolution in Health and Care?

Author: Désirée Larenas-Linnemann, Fulvio Braido, Paolo Maria Matricardi, Wienczyslawa Czarlewski, Alvaro A. Cruz, Sanna Toppila-Salmi, Oliver Pfaar, Dana Wallace, Torsten Zuberbier, Pascal Demoly, Olga Lourenço, Anna Bedbrook, Daniel Laune, Nhân Pham-Thi, Violeta Kvedariene, Piotr Kuna, Marina Erhola, Ignacio J. Ansotegui, Annabelle Bédard, V. Cardona, Salvadore Tripodi, Maria Teresa Ventura, João Fonseca, Nikos Papadopoulos, Michiel van Eerd, Maddalena Illario, Sylvie Arnavielhe, Juan Carlos Ivancevich, Peter Hellings, Gabrielle L. Onorato, Sinthia Bosnic-Anticevich, Ludger Klimek, Teresa To, Jean Bousquet, Arzu Yorgancioglu, W. J. Fokkens, Peter Valentin Tomazic, Xavier Basagaña, Erik Melén, Josep M. Antó, Arunas Valiulis, Matteo Bonini, Claus Bachert, Vesa Jormanainen, Aziz Sheikh, Stephanie Dramburg, Rachel Tan, Joaquim Mullol, Tari Haahtela, Eve Mathieu-Dupas, Govert De Vries, Ear, Nose and Throat, AII - Inflammatory diseases, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hospital Quiròn Bizkaia Erandio, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), KYomed INNOV, Ghent University Hospital, Università cattolica del Sacro Cuore [Roma] (Unicatt), Imperial College London, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Genoa (UNIGE), Vall d'Hebron University Hospital [Barcelona], UCB Pharma, Colombes, Universidade Federal da Bahia (UFBA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Peercode (Développement de l'application) Oudenhof 4c 4191 NW Geldermalsen, Pays-Bas., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), National Institute for Health and Welfare [Helsinki], European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), VU University Medical Center [Amsterdam], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto, University of Helsinki, University Hospitals Leuven [Leuven], University of Amsterdam [Amsterdam] (UvA), 'Federico II' University of Naples Medical School, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Medical University of Łódź (MUL), Vilnius University [Vilnius], Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Clínica de Alergia- Asma y Pediatría, Hospital Medica Sur, University of Beira Interior [Portugal] (UBI), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Transverse group for research in primary care [Barcelona], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Manchester [Manchester], University of Athens Medical School [Athens], Philipps University of Marburg, Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris], University of Edinburgh, The University of Sydney, Sidkkids Hospital and Institute of Health Policy (Management and Evaluation), Medical University Graz, Policlinico Casilino (Ospedale Policlinico Casilino), Nova Southeastern University (NSU), University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Humboldt-Universität zu Berlin, Bousquet, J., Ansotegui, I. J., Anto, J. M., Arnavielhe, S., Bachert, C., Basagana, X., Bedard, A., Bedbrook, A., Bonini, M., Bosnic-Anticevich, S., Braido, F., Cardona, V., Czarlewski, W., Cruz, A. A., Demoly, P., De Vries, G., Dramburg, S., Mathieu-Dupas, E., Erhola, M., Fokkens, W. J., Fonseca, J. A., Haahtela, T., Hellings, P. W., Illario, M., Ivancevich, J. C., Jormanainen, V., Klimek, L., Kuna, P., Kvedariene, V., Laune, D., Larenas-Linnemann, D., Lourenco, O., Onorato, G. L., Matricardi, P. M., Melen, E., Mullol, J., Papadopoulos, N. G., Pfaar, O., Pham-Thi, N., Sheikh, A., Tan, R., To, T., Tomazic, P. V., Toppila-Salmi, S., Tripodi, S., Wallace, D., Valiulis, A., van Eerd, M., Ventura, M. T., Yorgancioglu, A., Zuberbier, T., CCSD, Accord Elsevier, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hospital Quirónsalud Bizkaia [Bilbao], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Università degli studi di Genova = University of Genoa (UniGe), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universidade do Porto = University of Porto, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Philipps Universität Marburg = Philipps University of Marburg, Institut Pasteur [Paris] (IP), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Humboldt University Of Berlin, uBibliorum, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University Hospital, Montpellier, France, MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France, VIMA, INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, France, Euforea, Brussels, Belgium, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Department of Dermatology and Allergy, Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany, Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, Spain, ISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Hospital del Mar Research Institute, Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, KYomed INNOV, Montpellier, France, Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium, UOC Pneumologia, Istituto di Medicina Interna, F Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy, National Heart and Lung Institute, Royal Brompton Hospital & Imperial College London, London, United Kingdom, Woolcock Institute of Medical Research, University of Sydney, Glebe, NSW, Australia, Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, Australia, Department of Internal Medicine (DiMI), University of Genoa, Genova, Italy, IRCCS Ospedale Policlinico San Martino, Genova, Italy, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain, Medical Consulting Czarlewski, Levallois, France, ProAR—Nucleo de Excelencia em Asma, Federal University of Bahia, Salvador, Brazil, WHO GARD Planning Group, Salvador, Brazil, Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France, Equipe EPAR—IPLESP, Sorbonne Université, Paris, France, Peercode BV, Geldermalsen, Netherlands, Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité—University Medicine Berlin, Berlin, Germany, National Institute for Health and Welfare, Helsinki, Finland, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda, Porto, Portugal, Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland, Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R&D and DISMET), Naples, Italy, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Institute of Biomedical Sciences, Department of Pathology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Institute of Clinical Medicine, Clinic of Chest Diseases and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Faculty of Health Sciences and CICS—UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal, AG Molecular Allergology and Immunomodulation, Department of Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany, E. Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, Barcelona, Spain, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children's Hospital 'P&A Kyriakou', University of Athens, Athens, Greece, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität Marburg, Marburg, Germany, Allergy Department, Pasteur Institute, Paris, France, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, United Kingdom, Sidkkids Hospital and Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada, Department of General ORL, H&NS, Medical University of Graz, Graz, Austria, Allergy Unit, Policlinico Casilino, Rome, Italy, Nova Southeastern University, Fort Lauderdale, Fla, United States, Institute of Clinical Medicine, Clinic of Children's Diseases, Vilnius University, Vilnius, Lithuania, Institute of Health Sciences, Department of Public Health, Vilnius University, Vilnius, Lithuania, European Academy of Paediatrics (EAP/UEMS-SP), Brussels, Belgium, University of Bari Medical School, Unit of Geriatric Immunoallergology, Bari, Italy, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, Charité—Universitätsmedizin Berlin, Berlin, Germany, Corporate member of Freie Universität Berlin, Humboldt-Uniersität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Berlin, Germany, Member of GA2LEN, Berlin, Germany, and Centre Médical de l'Institut Pasteur
Subjects: SENTINEL NETWORK, Allergy, IMPACT, [SDV]Life Sciences [q-bio], digital transformation of health, 0302 clinical medicine, Risk Factors, Immunology and Allergy, Medicine, 030212 general & internal medicine, MASK-RHINITIS, mHealth, Rhiniti, media_common, Rhinitis, SMARTPHONE, WORK PRODUCTIVITY, Mobile Applications, Telemedicine, 3. Good health, [SDV] Life Sciences [q-bio], Europe, Digital transformation of health, Phenotype, General Data Protection Regulation, DISEASE SEVERITY, Smartphone, Life Sciences & Biomedicine, PHARMACOLOGICAL-TREATMENT, Human, Apps, MASK, Mobile technology, digital transformation of health, mHealth, rhinitis, MASK, Immunology, Internet privacy, Mobile Application, [INFO] Computer Science [cs], Clinical decision support system, MACVIA-ARIA, 03 medical and health sciences, ADHERENCE, rhinitis, Mobile technology, media_common.cataloged_instance, Humans, [INFO]Computer Science [cs], European union, App -MASK, Science & Technology, business.industry, Risk Factor, Digital transformation, Usability, Apps, Rhinitis, Allergic, Health care delivery, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, ASTHMA, business, App, Delivery of Health Care
Abstract: Smart devices and Internet-based applications (apps) are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability, and cost-effectiveness. Second, they should be evaluated in the frame of the digital transformation of health, their impact on health care delivery, and health outcomes. This review (1) summarizes some existing mobile health apps for allergic rhinitis and reviews those in which testing has been published, (2) discusses apps that include risk factors of allergic rhinitis, (3) examines the impact of mobile health apps in phenotype discovery, (4) provides real-world evidence for care pathways, and finally (5) discusses mobile health tools enabling the digital transformation of health and care, empowering citizens, and building a healthier society. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE vol:7 issue:8 pages:2511-2523 ispartof: location:United States status: published
Published: 2019

10. Natural killer cell infiltration is discriminative for antibody-mediated rejection and predicts outcome after kidney transplantation

Author: Dirk Kuypers, Evelyne Lerut, Pierre Marquet, Henriette de Loor, Wilfried Gwinner, Marie Essig, Stéphane Gazut, Frans Schuit, Dany Anglicheau, Jasper Callemeyn, Carole Saison, Leentje Van Lommel, Saleh Yazdani, Olivier Thaunat, Max Wevers, Ben Sprangers, Lieven Thorrez, Alice Koenig, Maarten Naesens, Line Heylen, Laure-Hélène Noël, Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, Laboratoire d'analyse des données et d'intelligence des systèmes (LADIS), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University Hospitals Leuven [Leuven], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gene Expression Unit, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Hannover Medical School [Hannover] (MHH), Département de Néphrologie [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), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 305499,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,BIOMARGIN(2013), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESSIG, Marie, and Biomarkers of renal graft injuries in kidney allograft recipients - BIOMARGIN - - EC:FP7:HEALTH2013-03-01 - 2017-02-28 - 305499 - VALID
Subjects: 0301 basic medicine, Graft Rejection, Male, Biopsy, Cell, 030232 urology & nephrology, Datasets as Topic, Kidney, Transcriptome, 0302 clinical medicine, Cytotoxic T cell, Kidney transplantation, Oligonucleotide Array Sequence Analysis, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], natural killer cells, Middle Aged, Allografts, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Treatment Outcome, Nephrology, antibody-mediated rejection, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Infiltration (medical), Adult, Cell type, kidney transplantation, survival, Antibodies, Natural killer cell, histology, 03 medical and health sciences, Young Adult, Immune system, Predictive Value of Tests, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Aged, business.industry, Gene Expression Profiling, Computational Biology, kid- ney transplantation, medicine.disease, 030104 developmental biology, Case-Control Studies, Immunology, gene expression, Kidney Failure, Chronic, business, Biomarkers
Abstract: Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways. CIBERSORT (Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts) deconvolution analysis was performed to elucidate the corresponding cell subtypes and showed increased NK cell infiltration in ABMR in comparison to TCMR and normal biopsies. Other leukocyte types (including monocytes/macrophages, CD4 and CD8 T cells, and dendritic cells) were increased in rejection, but could not discriminate ABMR from TCMR. Deconvolution-based estimation of NK cell infiltration was validated using computerized morphometry, and specifically associated with glomerulitis and peritubular capillaritis. In an external data set of kidney transplant biopsies, activated NK cell infiltration best predicted graft failure amongst all immune cell subtypes and even outperformed a histologic diagnosis of acute rejection. These data suggest that NK cells play a central role in the pathophysiology of ABMR and graft failure after kidney transplantation. ispartof: Kidney International vol:95 issue:1 pages:188-198 ispartof: location:United States status: published
Published: 2019

11. Diagnosis and management of asymptomatic bacteriuria in kidney transplant recipients

Author: Coussement, Julien, Maggiore, Umberto, Manuel, Oriol, Scemla, Anne, López-Medrano, Francisco, Nagler, Evi, Aguado, José María, Abramowicz, Daniel, Adams, Brigitte, Agnelli, Caroline, Ailioaie, Oana, Akan, Hamdi, Amrouche, Lucile, Andrés, Amado, Anglicheau, Dany, Arnouts, Paul, Baas, Marije, Balgradean, Cristian, Bammens, Bert, Battaglia, Yuri, Baudoux, Thomas, Berto, Bert, Binet, Isabelle, Bistrup, Claus, Bonofiglio, Renzo, Bosmans, Jean-Louis, Bouatou, Yassine, Bouvier, Nicolas, Braconnier, Philippe, Bredewold, Edwin, Broeders, Nilufer, BRUNET, Philippe, Buchler, Matthias, Budde, Klemens, Buron, Fanny, Burtey, Stephane, Buscaroli, Andrea, Büttner, Stefan, Byrne, Catherine, Caldara, Rossana, Cassuto, Elisabeth, Catalano, Concetta, Cavaille, Guilhem, Corbel, Alice, Couzi, Lionel, Crespo, Marta, Daga, Sunil, Debellé, Frederic, Dedinska, Ivana, Devine, Paul, Dickenmann, Michael, Dratwa, Max, Drgona, Lubos, Durlik, Magdalena, Egidi, Maria Francesca, Errasti, Pedro, Etienne, Isabelle, Fariñas, María Carmen, Fehr, Thomas, Fernández-Ruiz, Mario, Founta, Paraskevi, Fourtounas, Konstantinos, Frangou, Eleni, Frimat, Luc, Furian, Luc, Garjau, Maria, Garrigue, Valérie, Gatault, Philippe, Geddes, Colin, Gerlinger, Paul, Gheuens, Eric, Ghisdal, Lidia, Gibbs, Paul, Giral, Magali, Girerd, Sophie, Golshayan, Dela, Gompou, Athina, Grossi, Paolo Antonio, Guglielmetti, Gabriele, Guirado, Luis, Hadaya, Karine, Hazzan, Marc, Helbert, Mark, Hellemans, Rachel, Heller, Katharina, Heemann, Uwe, Henckes, Manu, Hernandez, Domingo, Hertig, Alexandre, Hiesse, Christian, Hilbrands, Luuk, Hilton, Rachel, Hirzel, Cédric, Horcajada, Juan Pablo, Hougardy, Jean-Michel, Huynh-Do, Uyen, Idrizi, Alma, Ismaili, Khalid, Jiménez, Carlos, Jourde-Chiche, Noemie, Kamar, Nassim, Kaminski, Hannah, Kanter, Julia, Karras, Alexandre, Kemlin, Delphine, Kes, Petar, Kianda, Mireille, Klinger, Maria, Knight, Simon, Koneth, Irene, Krrashi, Anita, Kuypers, Dirk, Langlois, Anne, Lang, Philippe, Lauzurica, Ricardo, Le Moine, Alain, Lebeaux, David, Legendre, Christophe, Lemy, Anne, Len, Oscar, Liakopoulos, Vassilios, Lichodziejewska-Niemierko, Monika, Yague, Maria, Lopau, Kai, Madhoun, Philippe, Magott-Procelewska, Maria, Malik, Shafi, Montero, Anna Manonelles, Marchini, Marc, Marega, Alessandra, Mariat, Maria, Mark, Mark, Martin, Pierre-Yves, Martín, Leyre, Martín, Paloma Leticia, Massart, Annick, Matignon, Marie, Maurel, Stéphane, Mazuecos, Auxiliadora, Melexopoulou, Christina, Melilli, Edoardo, Merino, Esperanza, Mesic, Enisa, Messa, Piergiorgio, Michalak, Magdalena, Minetti, Enrico, Miserlis, Grigorios, Montejo, Miguel, Moriconi, Diego, Mottola, Clément, Mourad, Georges, Mueller, Thomas, Muñoz, Patricia, Nabokow, Alexander, Naesens, Maarten, Nikodimopoulou, Maria, Oberbauer, Rainer, Olmedo, María, Olsburgh, Jonathon, Oniscu, Gabriel, Øzbay, Lara Aygen, Palmisano, Alessandra, Papagianni, Aikaterini, Papasotiriou, Mario, Parodi, Angelica, Parry, Rob, Pascual, Julio, Flores, Isabel Pérez, Pérez-Sáez, María, Peruzzi, Licia, Petit-Hoang, Camille, Phelan, Paul, Pillebout, Evangeline, Piotti, Giovanni, Pipeleers, Lissa, Pleros, Christos, Popoola, Joyce, Pretagostini, Renzo, Psimenou, Erasmia, Puig, Josep, Rafat, Cédric, Bloudickova, Silvie Rajnochova, Bushljetikj, Irena Rambabova, Ratkovic, Marina, Redondo, Dolores, Reischig, Tomas, Robert, Thomas, Ferrero, Luis, Rroji, Merita, Rutkowski, Przemyslaw, Rydzewska-Rosolowska, Alicja, Sabé, Núria, Sahali, Dil, Salzberger, Bernd, San-Juan, Rafael, Sobrino, Beatriz Sánchez, Sandrini, Silvio, Santos, Lídia, Sava, Roxana, Schaub, Stefan, Schikowski, Johan, Schvartz, Betoul, Sester, Urban, Silva, Jose Tiago, Snanoudj, Renaud, Somenzi, Danio, Sørensen, Søren, Spanos, Georgios, Steiger, Jürg, Suwelack, Barbara, Theodoropoulou, Eleni, Thervet, Eric, Thorban, Stefan, Tognarelli, Giuliana, Tournay, Yasmina, Tricot, Leïla, Tulissi, Patrizia, Vacher-Coponat, Henri, Valerio, Maricela, Van Der Meijden, W, Van Hamersvelt, Henk, Van Laecke, Steven, Vandivinit, Alain, Vanholder, Raymond, Veroux, Massimiliano, Viklicky, Ondrej, Vigo, Emanuela, Viscoli, Claudio, Watschinger, W, Weekers, W, Welberry Smith, W, Martin, W, Zeneli, Nereida, Zervos, Angelos, Zibar, Lada, Zuber, Julien, Zukunft, Bianca, Nephrology, Department Infections Diseases, Université Libre de Bruxelles [Bruxelles] (ULB), Azienda Ospedaliero-Universitaria di Parma, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Réseau CENTAURE, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Department of Nephrology, Humboldt Universität zu Berlin, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, Hôpital Pasteur [Nice] (CHU), Hôpital de Brabois, CHU de Nancy, Vandoeuvre-lès-Nancy, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire des interactions plantes micro-organismes (LIPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), CHU Rouen, Normandie Université (NU), Unit Infectious Diseases, Hospital 12 de Octubre, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Université de Lille, Department of Pulmonary Medicine, Tampere University Hospital, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Swiss Transplantation Cohort Study, University of Basel (Unibas), Department of Nephrology and Hypertension, and Department of Clinical Research, University of Bern, Centro de Investigación en Ciencias del Mar y Limnología (CIMAR), Universidad Nacional de Costa Rica, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Bordeaux (UB), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania [Philadelphia], Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherches Pétrographiques et Géochimiques (CRPG), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), 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), Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Milano, Université de Lorraine (UL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz, Clinical Microbiology and Infectious Diseases Department, Universidad Complutense de Madrid [Madrid] (UCM), University Hospitals Leuven [Leuven], Department of Internal Medicine III, Medizinische Universität Wien = Medical University of Vienna, Service de rhumatologie, Kidney and Pancreas Transplantation, Department d'enginyeria quimica agraria i tecnologia agroalimentaria, Universitat de Girona (UdG), Néphrologie Transplantation, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Section of Microbiology [Copenhagen], Department of Biology [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University Hospital Basel [Basel], Service Néphrologie Transplantation Rénale, Hôpital Foch [Suresnes], Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Renal Division, Freiburg University Medical Center, Nephrology Section [Ghent], Ghent University Hospital, Dept. of Nephrology, Institute for Clinical and Experimental Medicine, Division of Infectious Diseases, University of Genoa (UNIGE)-San Martino University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université libre de Bruxelles (ULB), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Humboldt University Of Berlin, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Université de Mons (UMons), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Pennsylvania, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Università degli studi di Genova = University of Genoa (UniGe)-San Martino University Hospital, ERA-EDTA, ESCMID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Humboldt-Universität zu Berlin, Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), and San Martino University Hospital-University of Genoa (UNIGE)
Subjects: Nephrology, Male, Cross-sectional study, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Practice Patterns, 030230 surgery, Antimicrobial stewardship, urologic and male genital diseases, 0302 clinical medicine, Surveys and Questionnaires, Bacteriuria/diagnosis, Medicine, Practice Patterns, Physicians'/statistics & numerical data, Practice Patterns, Physicians', Asymptomatic Infections, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Asymptomatic bacteriuria, Questionnaire, Transplantation, Urinary tract infection, Adult, Anti-Bacterial Agents, Bacteriuria, Cross-Sectional Studies, Europe, Female, Humans, Kidney Transplantation, Transplant Recipients, Response rate (survey), Kidney Transplantation/adverse effects, 16. Peace & justice, 3. Good health, medicine.medical_specialty, Asymptomatic Infections/epidemiology, Europe/epidemiology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Dialysis, Physicians', business.industry, medicine.disease, Anti-Bacterial Agents/therapeutic use, Human medicine, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract: Background Asymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs. Methods A panel of experts from the European Renal Association-European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs. Results Two hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27). Conclusions Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.
Published: 2018

12. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study

Author: Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, 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), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), 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 National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), 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)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], 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), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract: International audience
Published: 2023

13. Scar imaging in the dyssynchronous left ventricle: Accuracy of myocardial metabolism by positron emission tomography and function by echocardiographic strain

Author: Camilla Kjellstad Larsen, Elena Galli, Jürgen Duchenne, John M. Aalen, Caroline Stokke, Jan Gunnar Fjeld, Ganna Degtiarova, Piet Claus, Olivier Gheysens, Jorg Saberniak, Per Anton Sirnes, Erik Lyseggen, Jan Bogaert, Erik Kongsgaard, Martin Penicka, Jens-Uwe Voigt, Erwan Donal, Einar Hopp, Otto A. Smiseth, Oslo University Hospital [Oslo], University of Oslo (UiO), CHU Pontchaillou [Rennes], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Akershus University Hospital [Lørenskog], University Hospitals Leuven [Leuven], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fonds Wetenschappelijk Onderzoek, FWO: 12ZZN22N, FKM1832917N, KU Leuven: OT12/084, Helse Sør-Øst RHF, sorost, and Nasjonalforeningen for Folkehelsen
Subjects: Glucose metabolism, Positron emission tomography, Late gadolinium enhancement cardiac magnetic resonance, Heart Ventricles, Contrast Media, Gadolinium, Heart failure, Myocardial scar, Strain, Cardiac Resynchronization Therapy, Cicatrix, Dyssynchrony, Speckle tracking echocardiography, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fluorodeoxyglucose F18, Echocardiography, Positron-Emission Tomography, Humans, Prospective Studies, Cardiology and Cardiovascular Medicine
Abstract: PURPOSE: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. METHODS: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. RESULTS: Reduced FDG metabolism (10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC
Published: 2023

14. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study

Author: Alessandro D Santin, Ignace Vergote, Antonio González-Martín, Kathleen Moore, Ana Oaknin, Ignacio Romero, Sami Diab, Larry J Copeland, Bradley J Monk, Robert L Coleman, Thomas J Herzog, Jonathan Siegel, Linda Kasten, Andreas Schlicker, Anke Schulz, Karl Köchert, Annette O Walter, Barrett H Childs, Cem Elbi, Iurie Bulat, Institut Català de la Salut, [Santin AD] Yale School of Medicine, New Haven, CT, USA. [Vergote I] University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. [González-Martín A] Clinica Universidad de Navarra, Madrid, Spain. [Moore K] University of Oklahoma Health Sciences Center, Oklahoma, OK, USA. [Oaknin A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Romero I] Instituto Valenciano de Oncología, Valencia, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Science & Technology, Anticossos monoclonals - Ús terapèutic, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], BEVACIZUMAB, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Obstetrics & Gynecology, Obstetrics and Gynecology, aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::anticuerpos::inmunoconjugados [COMPUESTOS QUÍMICOS Y DROGAS], Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoconjugates [CHEMICALS AND DRUGS], Ovaris - Càncer - Tractament, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], CHEMOTHERAPY, Other subheadings::Other subheadings::/drug therapy [Other subheadings], ovarian cancer, Oncology, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], TRIAL, WEEKLY PACLITAXEL, TOPOTECAN, Life Sciences & Biomedicine
Abstract: ObjectivesAnetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer.MethodsAnetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing.ResultsIn dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months.ConclusionsAnetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.Trial registration numberNCT02751918.
Published: 2022

15. Sex differences in imaging and clinical characteristics of patients from the WAKE--UP trial

Author: Anke Wouters, Lauranne Scheldeman, Hannelore Liessens, Patrick Dupont, Florent Boutitie, Bastian Cheng, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Christian Gerloff, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Claus Z. Simonsen, Vincent Thijs, Götz Thomalla, Robin Lemmens, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Amsterdam UMC - Amsterdam University Medical Center, Leuven Brain Institute [Leuven, Belgium] (LBI), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Aarhus University Hospital, University of Melbourne, Austin Hospital [Melbourne], Austin Health, CarMeN, laboratoire, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Sex Characteristics, Time Factors, Ischemic stroke, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, methods [Thrombolytic Therapy], wake-up, drug therapy [Stroke], therapeutic use [Tissue Plasminogen Activator], Neurology, Wake-up, methods [Diffusion Magnetic Resonance Imaging], diagnostic imaging [Stroke], ischemic stroke, Humans, drug therapy [Brain Ischemia], sex, Female, Sex, ddc:610, Neurology (clinical), Mri, MRI
Abstract: BACKGROUND AND PURPOSE: Sex-based differences in acute ischemic stroke are a well-known phenomenon. We aimed to explore these differences between women and men in the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial. METHODS: We compared baseline demographic and imaging characteristics (visual fluid-attenuated inversion recovery [FLAIR] positivity, relative FLAIR signal intensity, collateral status) between women and men in all screened patients. In randomized patients (i.e., those with diffusion-weighted imaging (DWI)-FLAIR mismatch), we evaluated a modifying role of sex on the treatment effect of alteplase in multivariable logistic regression, with treatment adjusted for National Institute of Health Stroke Scale (NIHSS) score and age. Dependent variables were modified Rankin Scale (mRS) score of 0-1 at 90 days and distribution of mRS scores at 90 days. RESULTS: Of 1362 screened patients, 529 (38.8%) were women. Women were older than men, had higher baseline NIHSS scores and smoked less frequently. FLAIR positivity of the DWI lesion was equally present in women (174/529, 33.1%) and men (273/833, 33.3%; p = 1.00) and other imaging variables also did not differ between the sexes. In a total of 503 randomized patients, of whom 178 were women (35.4%), sex did not modify the treatment effect of alteplase on mRS score 0-1 or on the total distribution of mRS scores. CONCLUSION: As in many other stroke trials, more men than women were included in the WAKE-UP trial, but the presence of a visual DWI-FLAIR mismatch and the relative FLAIR signal intensity did not differ between the sexes. The treatment effect of alteplase was not modified by sex. ispartof: EUROPEAN JOURNAL OF NEUROLOGY vol:30 issue:3 pages:641-647 ispartof: location:England status: published
Published: 2023

16. Optical coherence tomography in coronary atherosclerosis assessment and intervention

Author: Makoto Araki, Seung-Jung Park, Harold L. Dauerman, Shiro Uemura, Jung-Sun Kim, Carlo Di Mario, Thomas W. Johnson, Giulio Guagliumi, Adnan Kastrati, Michael Joner, Niels Ramsing Holm, Fernando Alfonso, William Wijns, Tom Adriaenssens, Holger Nef, Gilles Rioufol, Nicolas Amabile, Geraud Souteyrand, Nicolas Meneveau, Edouard Gerbaud, Maksymilian P. Opolski, Nieves Gonzalo, Guillermo J. Tearney, Brett Bouma, Aaron D. Aguirre, Gary S. Mintz, Gregg W. Stone, Christos V. Bourantas, Lorenz Räber, Sebastiano Gili, Kyoichi Mizuno, Shigeki Kimura, Toshiro Shinke, Myeong-Ki Hong, Yangsoo Jang, Jin Man Cho, Bryan P. Yan, Italo Porto, Giampaolo Niccoli, Rocco A. Montone, Vikas Thondapu, Michail I. Papafaklis, Lampros K. Michalis, Harmony Reynolds, Jacqueline Saw, Peter Libby, Giora Weisz, Mario Iannaccone, Tommaso Gori, Konstantinos Toutouzas, Taishi Yonetsu, Yoshiyasu Minami, Masamichi Takano, O. Christopher Raffel, Osamu Kurihara, Tsunenari Soeda, Tomoyo Sugiyama, Hyung Oh Kim, Tetsumin Lee, Takumi Higuma, Akihiro Nakajima, Erika Yamamoto, Krzysztof L. Bryniarski, Luca Di Vito, Rocco Vergallo, Francesco Fracassi, Michele Russo, Lena M. Seegers, Iris McNulty, Sangjoon Park, Marc Feldman, Javier Escaned, Francesco Prati, Eloisa Arbustini, Fausto J. Pinto, Ron Waksman, Hector M. Garcia-Garcia, Akiko Maehara, Ziad Ali, Aloke V. Finn, Renu Virmani, Annapoorna S. Kini, Joost Daemen, Teruyoshi Kume, Kiyoshi Hibi, Atsushi Tanaka, Takashi Akasaka, Takashi Kubo, Satoshi Yasuda, Kevin Croce, Juan F. Granada, Amir Lerman, Abhiram Prasad, Evelyn Regar, Yoshihiko Saito, Mullasari Ajit Sankardas, Vijayakumar Subban, Neil J. Weissman, Yundai Chen, Bo Yu, Stephen J. Nicholls, Peter Barlis, Nick E. J. West, Armin Arbab-Zadeh, Jong Chul Ye, Jouke Dijkstra, Hang Lee, Jagat Narula, Filippo Crea, Sunao Nakamura, Tsunekazu Kakuta, James Fujimoto, Valentin Fuster, Ik-Kyung Jang, CarMeN, laboratoire, Massachusetts General Hospital [Boston, MA, USA], Harvard Medical School [Boston] (HMS), Asan Medical Center [Seoul, South Korea] (AMC), University of Vermont [Burlington], Kawasaki Medical School [Okayama, Japan] (KMS), Yonsei University College of Medicine [Seoul, South Korea] (YUCM), Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), University Hospitals Bristol, Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], Technische Universität München = Technical University of Munich (TUM), Munich Heart Alliance [Munich, Allemagne] (MHA), German Heart Center = Deutsches Herzzentrum München [Munich, Germany] (GHC), Aarhus University Hospital [Skejby, Denmark] (AUH), Hospital Universitario de La Princesa, National University of Ireland [Galway] (NUI Galway), University Hospitals Leuven [Leuven], Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), 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), Hospices Civils de Lyon (HCL), Université de Lyon, Institut Mutualiste de Montsouris (IMM), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute of Cardiology [Warsaw, Poland] (NIC), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Massachusetts General Hospital [Boston], Cardiovascular Research Foundation [New York, NY, USA] (CRF), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Barts Health NHS Trust [London, UK], Queen Mary University of London (QMUL), Bern University Hospital [Berne] (Inselspital), Centro Cardiologico Monzino [Milan, Italy] (2CM), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Mitsukoshi Health and Welfare Foundation [Tokyo, Japan] (MHWF), Yokohama Minami Kyosai Hospital [Kanagawa, Japan] (YMKH), Showa University Hospital [Tokyo, Japan] (SUH), Kyung Hee University [Seoul, South Korea] (KHU), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Genova = University of Genoa (UniGe), Università degli studi di Parma = University of Parma (UNIPR), Catholic University of the Sacred Heart [Rome, Italy] (CUSH), University Hospital [Ioannina, Greece] (UH), New York University School of Medicine (NYU Grossman School of Medicine), Vancouver General Hospital [Vancouver, British Columbia, Canada] (VGH), University of British Columbia (UBC), Brigham and Women’s Hospital [Boston, MA], New York Presbyterian Hospital, Columbia University Medical Center (CUMC), Columbia University [New York], Ospedale San Giovanni Bosco [Turin, Italy] (OSGB), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), National and Kapodistrian University of Athens (NKUA), Tokyo Medical and Dental University [Japan] (TMDU), Kitasato University, Nippon Medical School Chiba Hokusoh Hospital [Chiba, Japan] (NMSC2H), The Prince Charles Hospital, Nara Medical University [Nara, Japan] (NMU), Tsuchiura Kyodo General Hospital [Ibaraki, Japan] (TKGH), Japanese Red Cross Musashino Hospital [Tokyo], St. Marianna University School of Medicine [Kanagawa, Japan], Kyoto University Graduate School of Medicine [Kyoto, Japan] (KUGSM), Jagiellonian University - Medical College (JUMC), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Mazzoni Hospital [Ascoli Piceno, Italy] (MH), Korea Advanced Institute of Science and Technology (KAIST), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Saint Camillus International University of Health Sciences [Rome, Italy] (SCIUHS), Fondazione IRCCS Policlinico San Matteo [Pavia], Università degli Studi di Pavia = University of Pavia (UNIPV), Universidade de Lisboa = University of Lisbon (ULISBOA), MedStar Washington Hospital Center [Washington, DC, USA] (MedStar WHC), CV Path Institute [Gaithersburg, MD, USA] (CV-PI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Yokohama City University (YCU), Wakayama University, Tohoku University [Sendai], Mayo Clinic [Rochester, MN, USA], Mayo Clinic [Rochester], University hospital of Zurich [Zurich], Gifu University Graduate School of Medicine, Madras Medical Mission [Chennai, India] (3M), MedStar Health Research Institute [Washington, DC, USA] (MedStar-HRI), Chinese People's Liberation Army General Hospital [Beijing, China] (CPLAGH), Harbin Medical University [China] (HMU), Monash university, University of Melbourne, Royal Papworth Hospital [Cambridge, UK] (RPH), Johns Hopkins University (JHU), Leiden University Medical Center (LUMC), The Open University of Japan [Chiba] (OUJ), and Massachusetts Institute of Technology (MIT)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Cardiology and Cardiovascular Medicine
Abstract: Optical coherence tomography (OCT) has been widely adopted in research on coronary atherosclerosis and adopted clinically to optimize percutaneous coronary intervention. In this Review, Jang and colleagues summarize this rapidly progressing field, with the aim of standardizing the use of OCT in coronary atherosclerosis.Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.
Published: 2022

17. Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Author: Timothée Bruel, Karl Stéfic, Yann Nguyen, Donatella Toniutti, Isabelle Staropoli, Françoise Porrot, Florence Guivel-Benhassine, William-Henry Bolland, Delphine Planas, Jérôme Hadjadj, Lynda Handala, Cyril Planchais, Matthieu Prot, Etienne Simon-Lorière, Emmanuel André, Guy Baele, Lize Cuypers, Luc Mouthon, Hugo Mouquet, Julian Buchrieser, Aymeric Sève, Thierry Prazuck, Piet Maes, Benjamin Terrier, Laurent Hocqueloux, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du VIH [Tours] - laboratoire associé (CNR VIH), Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France / National Reference Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Régional d'Orléans (CHRO), Work in the O.S. lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and ANR Coronamito and IDISCOVR. Work in the UPBI facility is funded by grant ANR-10-INSB-04-01 and the Région Ȋle-de-France program DIM1Health. D.P. is supported by the Vaccine Research Institute. P.M. acknowledges the support of a COVID-19 research grant from 'Fonds Wetenschappelijk Onderzoek' /Research Foundation Flanders (grant G0H4420N) and 'Internal Funds KU Leuven' (grant 3M170314). E.S.-L. acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005)., We thank the European Health Emergency Preparedness and Response Authority (HERA) for supporting the work being done at Institut Pasteur and UK Leuven. We thank the patients who participated in this study. We thank members of the Virus and Immunity Unit for discussions and help. We thank Ludivine Grzelak for her help in creating an illustration of SARS-CoV-2 variant mutations. We thank N. Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis. The Opera system was co-funded by Institut Pasteur and the Région Ȋle-de-France (DIM1Health). We thank F. Peira, V. Legros, and L. Courtellemont for their help with the cohorts. UZ Leuven, as a national reference center for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged. We thank Hélène Péré and David Veyer for their help in sequencing viral strains and helpful discussions., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
Subjects: Omicron, SARS-CoV-2, Antibody-Dependent Cell Cytotoxicity, antibodies, Humans, COVID-19, Antibodies, Monoclonal, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, neutralization, ADCC, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology
Abstract: The emergence of novel Omicron lineages, such as BA.5, may impact the therapeutic efficacy of anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). Here, we evaluated the neutralization and ADCC activity of 6 therapeutic mAbs against Delta, BA.2, BA.4 and BA.5 isolates. The Omicron sub-variants escaped most of the antibodies but remained sensitive to Bebtelovimab and Cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 displayed identical neutralization profiles. Sotrovimab was the most efficient at eliciting ADCC. We also analyzed 121 sera from 40 immunocompromised individuals up to 6 months after infusion of 1200 mg of Ronapreve (Imdevimab + Casirivimab), and 300 or 600 mg of Evusheld (Cilgavimab + Tixagevimab). Sera from Ronapreve-treated individuals did not neutralize Omicron subvariants. Evusheld-treated individuals neutralized BA.2 and BA.5, but titers were reduced by 41- and 130-fold, respectively, compared to Delta. A longitudinal evaluation of sera from Evusheld-treated patients revealed a slow decay of mAb levels and neutralization. The decline was more rapid against BA.5. Our data shed light on the antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.
Published: 2022

18. Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial

Author: Patrick Schöffski, Suzanne George, Michael C. Heinrich, John R. Zalcberg, Sebastian Bauer, Hans Gelderblom, César Serrano, Robin L. Jones, Steven Attia, Gina D’Amato, Ping Chi, Peter Reichardt, Claus Becker, Kelvin Shi, Julie Meade, Rodrigo Ruiz-Soto, Jean-Yves Blay, Margaret von Mehren, Institut Català de la Salut, [Schöffski P] General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. [George S] Dana-Farber Cancer Institute, Boston, MA, USA. [Heinrich MC] VA Portland Veterans Health Care System, Portland, OR, USA. OHSU Knight Cancer Institute, Portland, OR, USA. [Zalcberg JR] Monash University and Alfred Health, VIC 3004 Melbourne, Australia. [Bauer S] Department of Medical Oncology, University Hospital Essen, Sarcoma Center/ West German Cancer Center, University Duisburg-Essen, Essen, Germany. Leiden University Medical Center, Leiden, Netherlands. [Gelderblom H] Leiden University Medical Center, Leiden, Netherlands. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Quality of life, Cancer Research, Gastrointestinal Stromal Tumors, Pacients - Satisfacció, Ripretinib, Medizin, Tub digestiu - Tumors - Tractament, Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Genetics, Humans, Gastrointestinal stromal tumors, Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires::Health Care Surveys::Patient Reported Outcome Measures [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Patient Reported Outcome Measures, Other subheadings::/therapeutic use [Other subheadings], enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal [ENFERMEDADES], técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios::encuestas sobre atención a la salud::medidas de resultados percibidos por los pacientes [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::/uso terapéutico [Otros calificadores], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Alopecia, Oncology, Patient-reported outcome measures, Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors [DISEASES], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
Abstract: Background Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL. Methods In the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL. Results Patients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P Conclusion PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia. Trial registration ClinicalTrials.gov Identifier: NCT03353753; first posted: November 27, 2017.
Published: 2022

19. Evolution of predator-prey interactions during range expansion in an aquatic insect predator

Author: José A. Carbonell, Ying‐Jie Wang, Arnaud Sentis, Robby Stoks, Universitair Ziekenhuis Leuven (UZ Leuven), Hospital Universitario Virgen Macarena [Séville], Risques, Ecosystèmes, Vulnérabilité, Environnement, Résilience (RECOVER), Aix Marseille Université (AMU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospitals Leuven [Leuven], and Universidad de Sevilla. Departamento de Zoología
Subjects: DYNAMICS, IMPACTS, LIFE-HISTORY, Science & Technology, Ecology, FUNCTIONAL-RESPONSE, Environmental Sciences & Ecology, GROWTH-RATE, eco-evolutionary dynamics, functional response, DEPENDENCE, [SDE]Environmental Sciences, EXPOSURE, thermal evolution, PLASTICITY, ADAPTATION, Life Sciences & Biomedicine, range expansion, TEMPERATURE, Ecology, Evolution, Behavior and Systematics, trophic interactions
Abstract: Many ectotherms are shifting their distributions polewards, which has been associated with the evolution of phenotypic traits and their thermal plasticity. Trophic interactions may determine the dynamics and ecological impact of range expansions. However, it is largely unknown how trait evolution in edge populations shapes trophic interactions. We studied evolutionary changes in the short-term (functional response) and long-term predator-prey interactions between an aquatic insect predator (the damselfly Ischnura elegans) and its prey (the water flea Daphnia magna) during the predator's ongoing poleward range expansion in northern Europe. Using a common-garden warming experiment at 20 and 24 degrees C we tested for differentiation between predator populations from edge and core regions in metabolic rate and functional response parameters, and used these empirical data to estimate the effects of range expansion on the short- and long-term predator-prey interaction strengths. Metabolic rates did not differ between populations from edge and core regions nor between rearing temperatures. Functional response parameters and their thermal plasticity showed signals of evolution during the range expansion. Attack rates did not differ between predators from edge and core regions, but only decreased under warming in predators from the edge region. Handling times decreased under warming in predators from the edge region but increased under warming in predators from the core region. While handling times were shorter in predators from the core region at 20 degrees C, these did not differ between regions at 24 degrees C. As a result, the short-term interaction strength was higher for predators from the core region at 20 degrees C, but not different between regions at 24 degrees C. The predator-prey system from the edge region showed lower long-term system stability at 20 degrees C, but this region difference disappeared under warming because the edge region stability then increased. Our results suggest that rapid evolution of functional response parameters during a predator's range expansion reduced the direct feeding impact on its prey and made the predator-prey system from the edge region more unstable, but not under warming. This provides rare evidence that functional responses can rapidly evolve during range expansions, potentially destabilizing food web dynamics. Read the free Plain Language Summary for this article on the Journal blog.
Published: 2022

20. Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials

Author: Michael, Rademacher, Manuel, Toledo, Wim, Van Paesschen, Kore K, Liow, Ivan G, Milanov, Maria-Luise, Esch, Nan, Wang, Merran, MacPherson, William J, Byrnes, Timothy D C, Minh, Elizabeth, Webster, Konrad J, Werhahn, Institut Català de la Salut, [Rademacher M] Department of Epileptology, University of Bonn Medical Center, Bonn, Germany. [Toledo M] Unitat d’Epilèpsia, Servei de Neurologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Van Paesschen W] Department of Neurology, University Hospitals Leuven, Leuven, Belgium. [Liow KK] Comprehensive Epilepsy Center, Hawaii Pacific Neuroscience, Honolulu, Hawaii, USA. [Milanov IG] Medical University of Sofia, Sofia, Bulgaria. [Esch ML] UCB Pharma, Monheim am Rhein, Germany, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adult, Drug Resistant Epilepsy, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos [FENÓMENOS Y PROCESOS], Clinical Neurology, administración de los servicios de salud::calidad de la atención sanitaria::evaluación de resultados y procesos (atención a la salud)::evaluación del desenlace (asistencia sanitaria)::resultado del tratamiento [ATENCIÓN DE SALUD], Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Epilepsy [DISEASES], Anticonvulsius - Ús terapèutic, antiepileptic drug, Seizures, dual mechanism of action, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance [PHENOMENA AND PROCESSES], Humans, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema nervioso central::anticonvulsivantes [COMPUESTOS QUÍMICOS Y DROGAS], antiseizure medication, tolerability, Resistència als medicaments, Science & Technology, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Anticonvulsants [CHEMICALS AND DRUGS], Neurosciences, synaptic vesicle protein 2, focal seizure, Epilèpsia - Tractament, Treatment Outcome, Neurology, Avaluació de resultats (Assistència sanitària), enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::epilepsia [ENFERMEDADES], Anticonvulsants, Drug Therapy, Combination, SEIZURES, Epilepsies, Partial, Neurosciences & Neurology, Neurology (clinical), Life Sciences & Biomedicine, Health Services Administration::Quality of Health Care::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment Outcome [HEALTH CARE]
Abstract: Antiepileptic drug; Antiseizure medication; Tolerability Fármaco antiepiléptico; Medicamento anticonvulsivo; Tolerabilidad Medicament antiepilèptic; Medicament anticonvulsiu; Tolerabilitat Objective To characterize efficacy, safety/tolerability, and pharmacokinetics of padsevonil (PSL) administered concomitantly with ≤3 antiseizure medications (ASMs) for observable focal seizures in adults with drug-resistant epilepsy in two multicenter, randomized, double-blind, placebo-controlled, parallel-group trials. Methods The phase 2b dose-finding trial (EP0091/NCT03373383) randomized patients 1:1:1:1:1 to PSL 50/100/200/400 mg or placebo twice daily (b.i.d.). The phase 3 efficacy trial (EP0092/NCT03739840) randomized patients 1:1:1:1 to PSL 100/200/400 mg or placebo b.i.d. Patients with observable (focal aware with motor symptoms, focal impaired awareness, focal to bilateral tonic–clonic) focal seizures for ≥3 years, experiencing them ≥4 times per 28 days including during the 4-week baseline period despite treatment with ≥4 lifetime ASMs including current ASMs, were enrolled. Results In EP0091 and EP0092, 410 and 231 patients, respectively, were randomized and received at least one dose of trial medication. In patients in EP0091 on PSL 50/100/200/400 mg b.i.d. (n = 80/82/81/81, respectively) versus placebo (n = 81), outcomes included percentage reductions over placebo in observable focal seizure frequency during the 12-week maintenance period: 17.2%, 19.1% (p = 0.128), 19.2% (p = 0.128), 12.4% (p = 0.248); 75% responder rates (p-values for odds ratios): 13.8%, 12.2% (p = 0.192), 11.1% (p = 0.192), 16.0% (p = 0.124) versus 6.2%; 50% responder rates: 33.8% (p = 0.045), 31.7% (p = 0.079), 25.9% (p = 0.338), 32.1% (p = 0.087), versus 21.0%; TEAEs were reported by 82.7% (67/81), 78.3% (65/83), 74.4% (61/82), 90.1% (73/81) versus 78.3% (65/83). In patients in EP0092 on PSL 100/200/400 mg b.i.d. (n = 60/56/56, respectively) versus placebo (n = 54), outcomes included percentage reductions over placebo: −5.6% (p = 0.687), 6.5% (p = 0.687), 6.3% (p = 0.687); 75% responder rates: 15.3% (p = 0.989), 12.5% (p = 0.989), 14.3% (p = 0.989) versus 13.0%; 50% responder rates: 35.6% (p = 0.425), 33.9% (p = 0.625), and 42.9% (p = 0.125) versus 27.8%; TEAEs were reported by 80.0% (48/60), 78.9% (45/57), 83.1% (49/59) versus 67.3% (37/55). Significance In both trials, the primary outcomes did not reach statistical significance in any PSL dose group compared with placebo. PSL was generally well tolerated, and no new safety signals were identified.
Published: 2022

21. Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Author: Eystein S Husebye, Frederik Castinetti, Sherwin Criseno, Giuseppe Curigliano, Brigitte Decallonne, Maria Fleseriu, Claire E Higham, Isabella Lupi, Stavroula A Paschou, Miklos Toth, Monique van der Kooij, Olaf M Dekkers, Haukeland University Hospital, University of Bergen (UiB), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], University Hospitals Birmingham [Birmingham, Royaume-Uni], Università degli Studi di Milano = University of Milan (UNIMI), University Hospitals Leuven [Leuven], Oregon Health and Science University [Portland] (OHSU), University of Manchester [Manchester], Pisa University Hospital, National and Kapodistrian University of Athens (NKUA), Semmelweis University [Budapest], Leiden University Medical Center (LUMC), and Universiteit Leiden
Subjects: Endocrinology, Drug-Related Side Effects and Adverse Reactions, Neoplasms, Endocrinology, Diabetes and Metabolism, Humans, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Hypophysitis, Endocrine System Diseases, Immune Checkpoint Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side-effects based on the Grading of Recommendations Assessment, Development, and Evaluation system. As these drugs have been used for a relatively short time, large systematic investigations are scarce. A systematic approach to diagnosis, treatment, and follow-up is needed, including baseline tests of endocrine function before each treatment cycle. We conclude that there is no clear evidence for the benefit of high-dose glucocorticoids to treat endocrine toxicities with the possible exceptions of severe thyroid eye disease and hypophysitis affecting the visual apparatus. With the exception of thyroiditis, most endocrine dysfunctions appear to be permanent regardless of ICI discontinuation. Thus, the development of endocrinopathies does not dictate a need to stop ICI treatment. ispartof: EUROPEAN JOURNAL OF ENDOCRINOLOGY vol:187 issue:6 pages:G1-G21 ispartof: location:England status: published
Published: 2022

22. Switch in FGFR 3 and 4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions.: Ontogeny of FGFR 3 and 4 in human kidney

Author: Mutsaers, Henricus, Levtchenko, Elena, Martinerie, Laetitia, Pertijs, Jeanne, Allegaert, Karel, Devriendt, Koenraad, Masereeuw, Rosalinde, Monnens, Leo, Lombes, Marc, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology and Toxicology, Radboud University Medical Center [Nijmegen], Department of Pediatrics & Department of Growth and Regeneration, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospitals Leuven [Leuven], departement of Pharmacology, Radboud University, Radboud University Medical Center [Nijmegen]-Radboud University Medical Center [Nijmegen], Centre for Human Genetics, Department of Physiology, PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Renal Association - European Dialysis and Transplant Association (ERA-EDTA, Fellowship no. ERA STF 132-2013, Grant Agreement 1801110N and 1800214N, respectively)., Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Katholieke Universiteit Leuven ( KU Leuven ) -University Hospitals Leuven [Leuven], and Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: musculoskeletal diseases, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Abstract: International audience; : Context: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. Objective: We strived to elucidate the evanescent nature of the observed hypercalcemia by studying the ontogenesis of FGFR3 and FGFR4 - which are both associated with FGF23-mediated mineral homeostasis - in the developing human kidney. Design: RT-qPCR and immunohistochemical analyses were used on archival human kidney samples to investigate expression of the FGFR signaling pathway during renal development. Results: We demonstrated that renal gene and protein expression of both FGFRs increased during fetal development between the gestational ages (GA) of 14-40 weeks. Yet, FGFR4 expression increased more rapidly as compared to FGFR3 (slope: 0.047 vs. 0.0075, p = 0.0018). Moreover, gene and protein expression of the essential FGFR co-receptor, Klotho, also increased with a significant positive correlation between FGFR and Klotho mRNA expression during renal development. Interestingly, we found that perinatal FGFR4 expression (GA 38-40 weeks) was 7-fold higher as compared to FGFR3 (p=0.0035), while in adult kidney tissues, FGFR4 gene expression level was more than 2-fold lower compared to FGFR3 (p=0.0029), thus identifying a molecular developmental switch of FGFR isoforms. Conclusion: We propose that the heterozygous FGFR4 deletion, as observed in the Sotos syndrome patient, leads to a compromised FGF23 signaling during infancy accounting for transient hypercalcemia. These findings represent a novel and intriguing view on FGF23-mediated calcium homeostasis.
Published: 2014

23. Providing care for older adults in the Emergency Department: expert clinical recommendations from the European Task Force on Geriatric Emergency Medicine

Author: R. McNamara, Christian H. Nickel, A. Thaur, Mehmet Akif Karamercan, B de Groot, Simon P. Mooijaart, Katrin Singler, Zerrin Defne Dundar, K. Y. Chueng, T. Gilbert, Áine Mitchell, Simon Conroy, F. Islam, L Van Der Linden, V. Mezera, S. Castejon, Pieter Heeren, Laura C. Blomaard, J A Lucke, Stephen Lim, [Lucke JA] Department of Emergency Medicine, Spaarne Gasthuis, Haarlem, The Netherlands. [Mooijaart SP] Department of Internal Medicine, Section on Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. [Heeren P] Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium. Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium. Research Foundation Flanders, Brussels, Belgium. [Singler K] Department of Geriatrics, Klinikum Nürnberg, Paracelsus Private, Medical University, Nuremberg, Germany. Institute for Biomedicine of Ageing, Friedrich-Alexander-University, Erlangen-Nuremberg, Erlangen, Germany. [McNamara R] Department of Emergency Medicine, St. Vincent's University Hospital, Dublin, Ireland. [Gilbert T] Department of Geriatric Medicine, Lyon-Sud University Hospital, Lyon, France. [Castejon S] Servei de Geriatria i Cures Pal·liatives, Hospital de Terrassa, Consorci Sanitari de Terrassa, Terrassa, Spain, and Consorci Sanitari de Terrassa
Subjects: medicine.medical_specialty, Health Care Facilities, Manpower, and Services::Health Facilities::Health Facility Administration::Hospital Administration::Hospital Departments::Emergency Service, Hospital [HEALTH CARE], Acute care, Guidelines, Special Article, Older patients, Humans, Medicine, Patient group, Geriatric Assessment, instalaciones, servicios y personal de asistencia sanitaria::centros sanitarios::administración de establecimientos sanitarios::administración hospitalaria::departamentos hospitalarios::servicio hospitalario de urgencias [ATENCIÓN DE SALUD], Aged, Geriatrics, Health Occupations::Medicine::Geriatrics [DISCIPLINES AND OCCUPATIONS], Frailty, business.industry, Task force, profesiones sanitarias::medicina::geriatría [DISCIPLINAS Y OCUPACIONES], Urgències mèdiques, Serveis d', Emergency department, Geriatric Emergency Medicine, Emergency medicine, Emergency Medicine, Delirium, medicine.symptom, Emergency Service, Hospital, Geriatria, business, End-of-life care
Abstract: Key summary points Aim The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. Findings Eight posters with expert clinical guidelines on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/. Message Expert clinical recommendations for Geriatric Emergency Medicine in Europe were created and are ready for dissemination across Europe. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00578-1., Purpose Despite the rapidly expanding knowledge in the field of Geriatric Emergency Medicine in Europe, widespread implementation of change is still lacking. Many opportunities in everyday clinical care are missed to improve care for this susceptible and growing patient group. The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. Methods A group of multi-disciplinary experts in the field of Geriatric Emergency Medicine in Europe was assembled. Using a modified Delphi procedure, a prioritized list of topics related to Geriatric Emergency Medicine was created. Next, a multi-disciplinary group of nurses, geriatricians and emergency physicians performed a review of recent guidelines and literature to create recommendations. These recommendations were voted upon by a group of experts and placed on visually attractive posters. The expert group identified the following eight subject areas to develop expert recommendations on: Comprehensive Geriatric Assessment in the Emergency Department (ED), age/frailty adjusted risk stratification, delirium and cognitive impairment, medication reviews in the ED for older adults, family involvement, ED environment, silver trauma, end of life care in the acute setting. Results Eight posters with expert clinical recommendations on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/. Conclusion Expert clinical recommendations for Geriatric Emergency Medicine may help to improve care for older patients in the Emergency Department and are ready for dissemination across Europe. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00578-1.
Published: 2021

24. Cost-Effectiveness of Magnetic Resonance Imaging-Guided Thrombolysis for Patients With Stroke With Unknown Time of Onset

Author: Alexander Konnopka, Louisa-Kristin Muntendorf, Jochen B. Fiebach, Norbert Nighoghossian, Keith W. Muir, Matthias Endres, Hans-Helmut König, Florent Boutitie, Vincent Thijs, Claus Z Simonsen, Götz Thomalla, Salvador Pedraza, Christian Gerloff, Robin Lemmens, Martin Ebinger, CarMeN, laboratoire, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Klinik für Neurologie, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany, Austin Health, University of Melbourne, The Florey Institute of Neuroscience and Mental Health, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Glasgow, 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), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), and Aarhus University Hospital
Subjects: thrombolysis, medicine.medical_specialty, Cost effectiveness, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, medicine.medical_treatment, Placebo, law.invention, methods [Magnetic Resonance Imaging], Randomized controlled trial, Modified Rankin Scale, law, economics [Thrombolytic Therapy], Acute care, economics [Magnetic Resonance Imaging], medicine, magnetic resonance imaging, Humans, methods [Cost-Benefit Analysis], Thrombolytic Therapy, ddc:610, cost-effectiveness, Stroke, quality-adjusted life-year, tissue-type plasminogen activator, health care economics and organizations, business.industry, Health Policy, Public Health, Environmental and Occupational Health, methods [Thrombolytic Therapy], Thrombolysis, medicine.disease, Magnetic Resonance Imaging, Markov Chains, Quality-adjusted life year, [SDV] Life Sciences [q-bio], Surgery, Computer-Assisted, Emergency medicine, Quality-Adjusted Life Years, business
Abstract: International audience; OBJECTIVES: Patients waking up with stroke symptoms are often excluded from intravenous thrombolysis with alteplase (IV-tpa). The WAKE-UP trial, a European multicenter randomized controlled trial, proved the clinical effectiveness of magnetic resonance imaging-guided IV-tpa for these patients. This analysis aimed to assess the cost-effectiveness of the intervention compared to placebo. METHODS: A Markov model was designed to analyze the cost-effectiveness over a 25-year time horizon. The model consisted of an inpatient acute care phase and a rest-of-life phase. Health states were defined by the modified Rankin Scale (mRS). Initial transition probabilities to mRS scores were based on WAKE-UP data and health state utilities on literature search. Costs were based on data from the University Medical Center Hamburg-Eppendorf, literature, and expert opinion. Incremental costs and effects over the patients' lifetime were estimated. The analysis was conducted from a formal German healthcare perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Treatment with IV-tpa resulted in cost savings of €51 009 and 1.30 incremental gains in quality-adjusted life-years at a 5% discount rate. Univariate sensitivity analysis revealed incremental cost-effectiveness ratio being sensitive to the relative risk of favorable outcome on mRS for placebo patients after stroke, the costs of long-term care for patients with mRS 4, and patient age at initial stroke event. In all cases, IV-tpa remained cost-effective. Probabilistic sensitivity analysis proved IV-tpa cost-effective in \textgreater95% of the simulations results. CONCLUSIONS: Magnetic resonance imaging-guided IV-tpa compared to placebo is cost-effective in patients with ischemic stroke with unknown time of onset.
Published: 2021

25. Multinational Observational Cohort Study of COVID-19–Associated Pulmonary Aspergillosis1

Author: Josje Altenburg, Roger J. M. Brüggemann, Yves Debavaye, Joost Wauters, Saad Nseir, Catherine S. C. Bouman, Julien Maizel, Taieb Chouaki, Albert Dunbar, Niels Van Regenmortel, Lynn Rutsaert, Bart J. A. Rijnders, Boualem Sendid, Damien Costa, Jeroen Schouten, Marijke Reynders, Fabienne Tamion, Simon Feys, Lore Vanderbeke, Hervé Dupont, Katrien Lagrou, Nico A F Janssen, Rémy Nyga, Paul E. Verweij, Karin van Dijk, Marc Bourgeois, Cato Jacobs, Hans I van der Spoel, Frank L. van de Veerdonk, Jochem B. Buil, Mehmet Ergün, Piet Lormans, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Pulmonary medicine, Intensive care medicine, AII - Inflammatory diseases, Medical Microbiology & Infectious Diseases, Internal Medicine, Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Lille, and Radboud University Medical Center [Nijmegen]
Subjects: Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], coronavirus, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], law.invention, respiratory infections, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, law, Internal medicine, risk factors, Medicine, viruses, SARS, SARS-CoV-2, invasive pulmonary aspergillosis, business.industry, Mortality rate, Incidence (epidemiology), COVID-19, Intensive care unit, zoonoses, Aspergillus, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, coronavirus disease, mortality rates, Cohort, mycology, epidemiology, Observational study, fungi, business, severe acute respiratory syndrome coronavirus 2, Cohort study
Abstract: We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%. ispartof: EMERGING INFECTIOUS DISEASES vol:27 issue:11 pages:2892-2898 ispartof: location:United States status: published
Published: 2021

26. Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol

Author: Cecile Faure‐Conter, Daniel Orbach, Hélène Sudour‐Bonnange, Cecile Verité, Ludovic Mansuy, Angelique Rome, Cecile Dumesnil, Estelle Thebaud, Marleen Renard, Frederic Hameury, Aude Flechon, Ellen Blanc, Frederique Dijoud, Brice Fresneau, Sylvie Chabaud, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospitals Leuven [Leuven], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Léon Bérard [Lyon], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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, Institut Gustave Roussy (IGR), Enfance et Santé, French paediatrics and adolescents cancer society, and Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent, SFCE
Subjects: Oncology, children, [SDV]Life Sciences [q-bio], Pediatrics, Perinatology and Child Health, germ cell tumours, Hematology, chemotherapy, tumour marker decline
Abstract: International audience; Background: Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more. Procedure: Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine–bleomycin–cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide–cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups. Results: One hundred fifteen patients were included: median age of 12.8 years (0.4–18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80–92) and 95% (89–98), respectively (median follow-up: 3.5 years, range: 0.2–5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84–93), 5-year OS 93% (89–95), p =.561). The 5-year EFS were 93% (95% CI: 80–98), 88% (71–95) and 79% (62–90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p =.02) according to the risk groups: 90% (66–97), 64% (30–85), 95% (72–99) and 87% (74–94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003–1.007). Conclusion: Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.
Published: 2022

27. Reduction of radiotoxicity by ultra-high dose rate protontherapy

Author: Saade, Gaëlle, Bogaerts, Eva, Chiavassa, Sophie, Blain, Guillaume, Delpon, Grégory, Evin, Manon, Ghannam, Youssef, Haddad, Ferid, Haustermans, Karin, Koumeir, Charbel, Macaeva, Ellina, Maigne, Lydia, Mouchard, Quentin, Servagent, Noël, Sterpin, Edmond, Supiot, Stéphane, Potiron, Vincent, Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), 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), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-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, GIP ARRONAX [Nantes], Université de Nantes (UN), University Hospitals Leuven [Leuven], Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Financial support from Inserm Cancer (PCSI FLASHMOD), Karen Kirkby, Marie-Catherine Vozenin, Núria Jornet Sala, Stephanie E. Combs, FLASHMOD, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)
Subjects: Protontherapy, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Ultra-high dose rate
Abstract: International audience
Published: 2022

28. Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Author: Delphine Planas, Timothée Bruel, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, Piet Maes, Ludivine Grzelak, Matthieu Prot, Said Mougari, Cyril Planchais, Julien Puech, Madelina Saliba, Riwan Sahraoui, Florent Fémy, Nathalie Morel, Jérémy Dufloo, Rafael Sanjuán, Hugo Mouquet, Emmanuel André, Laurent Hocqueloux, Etienne Simon-Loriere, David Veyer, Thierry Prazuck, Hélène Péré, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), I2SysBio (CSIC-UV), Universitat de València (UV), University Hospitals Leuven [Leuven], Centre Hospitalier Régional d'Orléans (CHRO), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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), Bruel, Timothee, Grzelak, Ludivine, Sanjuán, Rafael, Simon-Loriere, Etienne, Schwartz, Olivier, Institute for Integrative Systems Biology [Valencia] (i2sysbio), Spanish National Research Council (CSIC)-Universitat de València (UV), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM) EQU202003010172, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR / FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, HERA European funding, Sanofi and IDISCOVR. DP is supported by the Vaccine Research Institute. The E.S.-L. laboratory is funded by Institut Pasteur, the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005) and the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID). HERA European funding and the NIH PICREID (grant no U01AI151758). The Opera system was co-funded by Institut Pasteur and the Région ile de France (DIM1Health). Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. P.M. acknowledges the support of a COVID-19 research grant from ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation Flanders (grant G0H4420N) and ‘Internal Funds KU Leuven’ (grant 3M170314)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), and ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
Subjects: Multidisciplinary, Breakthrough Infections, SARS-CoV-2, [SDV]Life Sciences [q-bio], General Physics and Astronomy, COVID-19, General Chemistry, Antibodies, Viral, Antibodies, Neutralizing, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Spike Glycoprotein, Coronavirus, Humans, BNT162 Vaccine
Abstract: Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.
Published: 2022

29. Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos

Author: Gaëlle Saade, Eva Bogaerts, Sophie Chiavassa, Guillaume Blain, Grégory Delpon, Manon Evin, Youssef Ghannam, Ferid Haddad, Karin Haustermans, Charbel Koumeir, Ellina Macaeva, Lydia Maigne, Quentin Mouchard, Noël Servagent, Edmond Sterpin, Stéphane Supiot, Vincent Potiron, Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), 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), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-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, GIP ARRONAX [Nantes], Université de Nantes (UN), University Hospitals Leuven [Leuven], Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), 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), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), This work was supported by Inserm Cancer, the Ligue Contre le Cancer, IRC Transformed, Institut de Cancérologie de l’Ouest, the Stichting Tegen Kanker (STK) grant ZKD6219, and the Walloon region EPT grant D7.21214.014-P., FLASHMOD, and UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
Subjects: Oncology, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Nuclear Medicine and imaging, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract: International audience; PurposeRecently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called “Flash” effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner.Methods and MaterialsIn this study, zebrafish embryos were used to compare the effect of UHDR irradiation (8-9 kGy/s) to conventional RT dose rate (0.2 Gy/s) with a 68 MeV proton beam. Viability, body length, spine curvature, and pericardial edema were measured 4 days postirradiation.ResultsWe show that body length is significantly greater after UHDR-RT compared with conventional RT by 180 µm at 30 Gy and 90 µm at 40 Gy, while pericardial edema is only reduced at 30 Gy. No differences were obtained in terms of survival or spine curvature.ConclusionsZebrafish embryo length appears as a robust endpoint, and we anticipate that this model will substantially fasten the study of UHDR proton-beam parameters necessary for “Flash.”
Published: 2022

30. Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism

Author: Flora Magnotti, Daria Chirita, Sarah Dalmon, Amandine Martin, Pauline Bronnec, Jeremy Sousa, Olivier Helynck, Wonyong Lee, Daniel L. Kastner, Jae Jin Chae, Michael F. McDermott, Alexandre Belot, Michel Popoff, Pascal Sève, Sophie Georgin-Lavialle, Hélène Munier-Lehmann, Tu Anh Tran, Ellen De Langhe, Carine Wouters, Yvan Jamilloux, Thomas Henry, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biocatalyse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), National Institutes of Health [Bethesda] (NIH), University of Leeds, Lyon Immunopathology Federation (LIFe), Hospices Civils de Lyon (HCL), Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris] (IP), 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), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, This work is supported by an ANR grant (FMFgeneToDiag). This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 779295. T.H.’s team is supported by The Fondation pour la Recherche Médicale (FRM EQU202103012640). D.C. is supported by a fellowship from The Fondation pour la Recherche Médicale (FDT202106012874). E.D.L. and C.W. are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases—Project ID no. 739543., ANR-17-CE17-0021,FMFgeneToDiag,Fièvre Méditerranéenne Familiale (FMF) et maladies apparentées : des bases moléculaires et cellulaires à la mise au point de tests diagnostiques(2017), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Henry, Thomas, and Fièvre Méditerranéenne Familiale (FMF) et maladies apparentées : des bases moléculaires et cellulaires à la mise au point de tests diagnostiques - - FMFgeneToDiag2017 - ANR-17-CE17-0021 - AAPG2017 - VALID
Subjects: Molecular biology [CP], MESH: Mutation, [SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammasomes, MESH: Testosterone, PAAND, progesterone, General Biochemistry, Genetics and Molecular Biology, catabolite, B30.2, autoinflammatory disease, familial Mediterranean fever, inflammasome, pyrin, MESH: Progesterone, Etiocholanolone, Humans, Testosterone, MESH: Humans, steroid, CP: Immunology, MESH: Pregnanolone, MESH: Etiocholanolone, Mutation, Immunology [CP], [SDV.IMM]Life Sciences [q-bio]/Immunology, CP: Molecular biology, pregnanolone
Abstract: The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identifies etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step 2 activators. High concentrations of these metabolites fully and rapidly activate pyrin, in a human specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) and familial Mediterranean fever (FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, display increased responses to these metabolites. This study identifies an unconventional pyrin activation mechanism, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the "steroid fever" described in the late 1950s upon steroid injection in humans. ispartof: CELL REPORTS vol:41 issue:2 ispartof: location:United States status: published
Published: 2022

31. Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer

Author: Hans Wildiers, Cristina Saura, Alshad S. Lalani, William J. Gradishar, Ana Vivancos, Sung-Bae Kim, Eduardo Cronemberger, Gerald J. Wallweber, Geraldo Silva Queiroz, Judith Bebchuk, Adam M. Brufksy, Richard A. Bryce, Beverly Moy, Suzette Delaloge, Lisa D. Eli, S Waters, Sara A. Hurvitz, Mafalda Oliveira, Judit Matito, Kiana Keyvanjah, Institut Català de la Salut, [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Innovative Breast Cancer Research, Barcelona, Spain. [Matito J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Wildiers H] University Hospitals Leuven, Leuven, Belgium. [Brufksy AM] Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania. [Waters SH] Velindre Cancer Centre, Cardiff, Wales, United Kingdom. [Vivancos A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. SOLTI Innovative Breast Cancer Research, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS], Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Lapatinib, Quimioteràpia combinada, Capecitabine, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, In patient, Neoplasm Metastasis, Biological Factors::Biomarkers::Biomarkers, Tumor [CHEMICALS AND DRUGS], Correlation of Data, skin and connective tissue diseases, neoplasms, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], business.industry, Proportional hazards model, Marcadors tumorals, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease, Metastatic breast cancer, Confidence interval, Retreatment, Mama - Càncer - Tractament, Neratinib, Quinolines, Immunohistochemistry, Female, business, medicine.drug
Abstract: Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS. Patients and Methods: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models. Results: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64–1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97–3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54–0.82); H-score ≥240 versus Conclusions: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C.
Published: 2021

32. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Author: Hope S. Rugo, Sara M. Tolaney, Delphine Loirat, Kevin Punie, Aditya Bardia, Sara A. Hurvitz, Joyce O’Shaughnessy, Javier Cortés, Véronique Diéras, Lisa A. Carey, Luca Gianni, Martine J. Piccart, Sibylle Loibl, David M. Goldenberg, Quan Hong, Martin Olivo, Loretta M. Itri, Kevin Kalinsky, Institut Català de la Salut, [Rugo HS] Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. [Tolaney SM] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Loirat D] Department of Medical Oncology and D3i, Institut Curie, Paris, France. [Punie K] Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. [Bardia A] Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. [Hurvitz SA] Medical Oncology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. [Cortés J] International Breast Cancer Center (IBCC), Quiron Group, Madrid & Barcelona, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: neoplasias::procesos neoplásicos::recurrencia neoplásica local [ENFERMEDADES], Clinical Trials and Supportive Activities, Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], Metàstasi, Oncology, Clinical Research, Breast Cancer, Mama - Càncer - Tractament, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], Genetics, Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local [DISEASES], Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Patient Safety, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], Cancer
Abstract: Breast cancer; Drug safety Càncer de mama; Seguretat dels medicaments Cáncer de mama; Seguridad de los medicamentos Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician’s choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG. This study was sponsored by Immunomedics, Inc., a subsidiary of Gilead Sciences, Inc. We thank the ASCENT patients, their caregivers, study investigators, and team members. We thank William A. Wegener, MD, PhD, Robert M. Sharkey, PhD, and Pius Maliakal, PhD, former employees of Immunomedics, for their contributions to the development of the ASCENT protocol and the clinical development of sacituzumab govitecan. Medical writing and editorial assistance were provided by Robert Rydzewski, MS, CMPP, and Shala Thomas, PhD, CMPP, of Team 9 Science, and funded by Immunomedics, Inc., a subsidiary of Gilead Sciences, Inc.
Published: 2022

33. Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer

Author: Sibylle Loibl, Delphine Loirat, Sara M. Tolaney, Kevin Punie, Mafalda Oliveira, Hope S. Rugo, Aditya Bardia, Sara A. Hurvitz, Adam M. Brufsky, Kevin Kalinsky, Javier Cortés, Joyce A. O'Shaughnessy, Véronique Dieras, Lisa A. Carey, Luca Gianni, Mahdi Gharaibeh, Luciana Preger, See Phan, Lawrence Chang, Ling Shi, Martine J. Piccart, Institut Català de la Salut, [Loibl S] Hämatologisch-Onkologische Gemeinschaftspraxis Am Bethanien-Krankenhaus, Frankfurt, Germany. [Loirat D] Medical Oncology Department and D3i, Institut Curie, Paris, France. [Tolaney SM] Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Punie K] Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. [Oliveira M] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Breast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Rugo HS] Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Health Status::Quality of Life [HEALTH CARE], Oncology, Mama - Càncer - Tractament, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::anticuerpos::inmunoconjugados [COMPUESTOS QUÍMICOS Y DROGAS], Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoconjugates [CHEMICALS AND DRUGS], Immunoglobulines - Ús terapèutic, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Qualitat de vida - Avaluació, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], ambiente y salud pública::salud pública::medidas epidemiológicas::demografía::estado de salud::calidad de vida [ATENCIÓN DE SALUD]
Abstract: Quality of life; Sacituzumab govitecan; Triple-negative breast neoplasms Qualitat de vida; Sacituzumab govitecan; Neoplàsies de mama triple negatiu Calidad de vida; Sacituzumab govitecan; Neoplasias de mama triple negativo Background The antibody–drug conjugate sacituzumab govitecan (SG) prolongs progression-free survival and overall survival in patients with refractory/relapsed metastatic triple-negative breast cancer (mTNBC). Here, we investigated its effect on health-related quality of life (HRQoL). Methods This analysis was based on the open-label phase III ASCENT trial (NCT02574455). Adults with refractory/relapsed mTNBC who had received ≥2 prior systemic therapies (≥1 in the metastatic setting) were randomised 1:1 to SG or treatment of physician's choice (TPC; capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed on day 1 of each treatment cycle using the EORTC QLQ-C30. Score changes from baseline were analysed using linear mixed-effect models for repeated measures. Stratified Cox regressions evaluated time to first clinically meaningful change of HRQoL. Results The analysis population comprised 236 patients randomised to SG and 183 to TPC. For global health status (GHS)/QoL, physical functioning, fatigue, and pain, changes from baseline were superior for SG versus TPC. Compared with TPC, SG was inferior regarding changes from baseline for nausea/vomiting and diarrhoea but non-inferior for other QLQ-C30 domains. Median time to first clinically meaningful worsening was longer for SG than for TPC for physical functioning (22.1 versus 12.1 weeks, P < 0.001), role functioning (11.4 versus 7.1 weeks, P < 0.001), fatigue (7.7 versus 6.0 weeks, P < 0.05), and pain (21.6 versus 9.9 weeks, P < 0.001). Conclusions SG was generally associated with greater improvements and delayed worsening of HRQoL scores compared with TPC. This supports the favourable profile of SG as an mTNBC treatment. This work was sponsored by Gilead Sciences.
Published: 2022

34. European Respiratory Society statement on long COVID follow-up

Author: Katerina M. Antoniou, Eirini Vasarmidi, Anne-Marie Russell, Claire Andrejak, Bruno Crestani, Marion Delcroix, Anh Tuan Dinh-Xuan, Venerino Poletti, Nicola Sverzellati, Michele Vitacca, Martin Witzenrath, Thomy Tonia, Antonio Spanevello, DESSAIVRE, Louise, University of Crete [Heraklion] (UOC), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Exeter Medical School, University of Exeter, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hôpital Cochin [AP-HP], G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Aarhus University Hospital, Università degli studi di Parma = University of Parma (UNIPR), Istituti Clinici Scientifici Maugeri IRCCS [Brescia], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Bern, and Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria)
Subjects: Pulmonary and Respiratory Medicine, Post-Acute COVID-19 Syndrome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, Quality of Life, COVID-19, Humans, COVID-19/complications, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Patients diagnosed with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aimed to identify optimal strategies for follow-up care that may positively impact the patient's quality of life (QoL). A European Respiratory Society (ERS) Task Force convened and prioritised eight clinical questions. A targeted search of the literature defined the timeline of "long COVID" as 1-6 months post-infection and identified clinical evidence in the follow-up of patients. Studies meeting the inclusion criteria report an association of characteristics of acute infection with persistent symptoms, thromboembolic events in the follow-up period, and evaluations of pulmonary physiology and imaging. Importantly, this statement reviews QoL consequences, symptom burden, disability and home care follow-up. Overall, the evidence for follow-up care for patients with long COVID is limited. ispartof: EUROPEAN RESPIRATORY JOURNAL vol:60 issue:2 ispartof: location:England status: published
Published: 2022

35. Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

Author: Lara Chavaz, Geert O. Janssens, Stephanie Bolle, Henry Mandeville, Monica Ramos-Albiac, Karen Van Beek, Helen Benghiat, Bianca Hoeben, Andres Morales La Madrid, Clemens Seidel, Rolf-Dieter Kortmann, Darren Hargrave, Lorenza Gandola, Emilia Pecori, Dannis G. van Vuurden, Veronica Biassoni, Maura Massimino, Christof M. Kramm, Andre O. von Bueren, CCA - Cancer Treatment and quality of life, Institut Català de la Salut, [Chavaz L] Department of Pediatrics, Gynecology and Obstetrics, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland. Cansearch Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland. [Janssens GO] Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands. Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands. [Bolle S] Department of Radiation Oncology, Gustave Roussy, Paris Saclay University, Villejuif, France. [Mandeville H] Department of Radiotherapy, The Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom. [Ramos-Albiac M] Servei d’Oncologia Radioteràpica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Van Beek K] Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium, and Vall d'Hebron Barcelona Hospital Campus
Subjects: re-irradiation (re-RT), child, Cancer Research, Càncer - Radioteràpia, Science & Technology, Other subheadings::Other subheadings::/radiotherapy [Other subheadings], Otros calificadores::Otros calificadores::/radioterapia [Otros calificadores], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma [ENFERMEDADES], Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma [DISEASES], Oncology, Gliomes, diffuse intrinsic pontine glioma (DIPG), adolescent, Avaluació de resultats (Assistència sanitària), RADIATION, Life Sciences & Biomedicine, radiotherapy
Abstract: PurposeThe aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression.MethodsWe carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus on the neurological triad (cranial nerve deficits, ataxia, and long tract signs). Patients were categorized as “responding” or “non-responding” to re-RT. To assess the interdependence between patients’ characteristics and clinical benefits, we used a chi-square or Fisher’s exact test. Survival according to clinical response to re-RT was calculated by the Kaplan–Meier method.ResultsAs earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well-documented patients, 44% (n = 11/25) had improvement in cranial nerve palsies, 40% (n = 10/25) had improvement in long-tract signs, and 44% (11/25) had improvement in cerebellar signs. Clinical benefits were observed in at least 1, 2, or 3 out of 3 symptoms of the DIPG triad, in 64%, 40%, and 24%, respectively. Patients irradiated with a dose ≥20 Gy versus p-value = 0.028). The survival from the start of re-RT to death was not different between responding and non-responding DIPG patients (p-value = 0.871).ConclusionA median re-irradiation dose of 20 Gy provides a neurological benefit in two-thirds of patients with an improvement of at least one symptom of the triad. DIPG patients receiving ≥20 Gy appear to improve slightly better with regard to ataxia; however, we need more data to determine whether dose escalation up to 30 Gy provides additional benefits.
Published: 2022

36. FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects

Author: Auriane Cospain, Ana Rivera-Barahona, Erwan Dumontet, Blanca Gener, Isabelle Bailleul-Forestier, Isabelle Meyts, Guillaume Jouret, Bertrand Isidor, Carole Brewer, Wim Wuyts, Leen Moens, Selket Delafontaine, Wayne Wing Keung Lam, Kris Van Den Bogaert, Anneleen Boogaerts, Emmanuel Scalais, Thomas Besnard, Benjamin Cogne, Christophe Guissard, Paul Rollier, Wilfrid Carre, Regis Bouvet, Karin Tarte, Ricardo Gómez-Carmona, Pablo Lapunzina, Sylvie Odent, Marie Faoucher, Christele Dubourg, Víctor L. Ruiz-Pérez, Koen Devriendt, Laurent Pasquier, Luis A. Pérez-Jurado, Generalitat de Catalunya, CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], Universidad Autónoma de Madrid (UAM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Microbiology, Immunology and Transplantation [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Laboratoire National de Santé [Luxembourg] (LNS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Antwerp University Hospital [Edegem] (UZA), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universitat Pompeu Fabra [Barcelona] (UPF), and Research reported in this publication was supported by the CatalonianDepartment of Health (URDCAT: Grant SLT002/16/00174) and the ENoD Programme of CIBERER(ER16P08), Instituto de Salud Carlos III. Selket Delafontaine is supported by the personal FWO Grant11F4421N. Isabelle Meyts is a Senior Clinical Investigator at the Research Foundation – Flanders, andis supported by the CSL Behring Chair of Primary Immunodeficiencies, by the KU Leuven C1 GrantC16/18/007, by a VIB GC PID Grant, by the FWO Grants G0C8517N, G0B5120N and G0E8420N and bythe Jeffrey Modell Foundation. Part of this work was supported by a grant from the Spanish Ministryof Science and Innovation (PID2019-105620RB-I00/AEI/10.13039/501100011033). The project hasalso received funding from the European Research Council (ERC) under the European Union’s Horizon2020 research and innovation programme (grant agreement No. 948959). This work is supported byERN-RITA.LAPJ is founding partner and scientific advisor of qGenomics Laboratories. The remaining authorsdeclare no potential conflict of interest.
Subjects: FOSL2 FRA-2 aplasia cutis congenita of scalp enamel hypoplasia AP-1 complex Adams-Oliver syndrome, Autism Spectrum Disorder, MESH: Fos-Related Antigen-2, FOSL2, Fos-Related Antigen-2, MESH: Scalp, Adams-Oliver syndrome, Ectodermal Dysplasia, AP-1 complex, Humans, RNA, Messenger, Genetics (clinical), FRA-2, MESH: Neurodevelopmental Disorders, MESH: RNA, Messenger, enamel hypoplasia, MESH: Autism Spectrum Disorder, MESH: Humans, MESH: Ectodermal Dysplasia, Scalp, Exons, MESH: Transcription Factor AP-1, Transcription Factor AP-1, aplasia cutis congenita of scalp, HEK293 Cells, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, MESH: HEK293 Cells, Human medicine, MESH: Exons
Abstract: [Purpose]: We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex., [Methods]: Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction. In vitro coimmunoprecipitation and proteasome inhibition assays in transfected HEK293 cells were performed to explore protein and AP-1 complex stability., [Results]: We identified 11 individuals from 10 families with mostly de novo truncating FOSL2 variants sharing a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts. Mutant FOSL2 messenger RNAs escaped nonsense-mediated messenger RNA decay. Truncated FOSL2 interacts with c-JUN, thus mutated AP-1 complexes could be formed., [Conclusion]: Truncating variants in the last exon of FOSL2 associate a distinct clinical phenotype by altering the regulatory degradation of the AP-1 complex. These findings reveal a new role for FOSL2 in human pathology., Research reported in this publication was supported by the Catalonian Department of Health (URDCAT).
Published: 2022

37. Contribution of Liver Stiffness Measurement by Vibration-Controlled Transient Elastography to Outcome Prediction in Primary Biliary Cholangitis

Author: Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John, Osman, Karim, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, 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), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], University of Toronto, University of Alberta, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, University of Barcelona, Mayo Clinic [Rochester], University Hospital of Larissa, University Hospitals Leuven [Leuven], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), University of Birmingham [Birmingham], Royal Free Hospital [London, UK], Università degli studi di Palermo - University of Palermo, CHU Bordeaux [Bordeaux], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Università del Piemonte Orientale - Dipartimento DISIT Italy, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Tel Aviv Sourasky Medical Center [Te Aviv], University hospital of Zurich [Zurich], Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Newcastle University [Newcastle], and HAL-SU, Gestionnaire
Subjects: Transplantation, FibroScan, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mortality, PBC, Prognosis
Abstract: International audience; Background & aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study.Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis.Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p
Published: 2022

38. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation

Author: Lidia Yshii, Emanuela Pasciuto, Pascal Bielefeld, Loriana Mascali, Pierre Lemaitre, Marika Marino, James Dooley, Lubna Kouser, Stijn Verschoren, Vasiliki Lagou, Hannelore Kemps, Pascal Gervois, Antina de Boer, Oliver T. Burton, Jérôme Wahis, Jens Verhaert, Samar H. K. Tareen, Carlos P. Roca, Kailash Singh, Carly E. Whyte, Axelle Kerstens, Zsuzsanna Callaerts-Vegh, Suresh Poovathingal, Teresa Prezzemolo, Keimpe Wierda, Amy Dashwood, Junhua Xie, Elien Van Wonterghem, Eline Creemers, Meryem Aloulou, Willy Gsell, Oihane Abiega, Sebastian Munck, Roosmarijn E. Vandenbroucke, Annelies Bronckaers, Robin Lemmens, Bart De Strooper, Ludo Van Den Bosch, Uwe Himmelreich, Carlos P. Fitzsimons, Matthew G. Holt, Adrian Liston, Pasciuto, Emanuela [0000-0002-5391-9585], Marino, Marika [0000-0001-6773-6176], Dooley, James [0000-0003-3154-4708], Verschoren, Stijn [0000-0001-6733-3481], Kemps, Hannelore [0000-0001-9248-1697], Gervois, Pascal [0000-0002-8320-1320], Burton, Oliver T [0000-0003-3884-7373], Singh, Kailash [0000-0002-6771-7757], Whyte, Carly E [0000-0001-6556-6855], Callaerts-Vegh, Zsuzsanna [0000-0001-9091-2078], Dashwood, Amy [0000-0002-4340-377X], Gsell, Willy [0000-0001-7334-6107], Vandenbroucke, Roosmarijn E [0000-0002-8327-620X], Liston, Adrian [0000-0002-6272-4085], Apollo - University of Cambridge Repository, Benson-Rumiz, Alicia, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Amsterdam [Amsterdam] (UvA), The Babraham Institute [Cambridge, UK], Brunel University London [Uxbridge], Hasselt University (UHasselt), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), VIB [Belgium], VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), Universiteit Gent = Ghent University (UGENT), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospitals Leuven [Leuven], University College of London [London] (UCL), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Pasciuto, Emanuela/0000-0002-5391-9585, Aloulou, Meryem/0000-0003-4590-230X, Dooley, James/0000-0003-3154-4708, Verschoren, Stijn/0000-0001-6733-3481, Kemps, Hannelore/0000-0001-9248-1697, Marino, Marika/0000-0001-6773-6176, Lemaitre, Pierre/0000-0003-0687-8685, Structural and Functional Plasticity of the nervous system (SILS, FNWI), SILS Other Research (FNWI), and Instituto de Investigação e Inovação em Saúde
Subjects: EXPRESSION, Immunology, Neuroimmunology, 631/250/127/1213, THERAPY, T-Lymphocytes, Regulatory, MICROGLIA, Mice, Medicine and Health Sciences, Immunology and Allergy, Animals, Humans, Interleukin-2 / genetics, REPAIR, Biological Products, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Interleukins, article, Biology and Life Sciences, 631/250/371, Brain, 631/250/251, REG-CELLS, Regulatory T cells, Astrocytes, 631/250/1619/554/1898/1271, Neuroinflammatory Diseases, Interleukin-2, Immunotherapy, SYSTEM, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, PACKAGE
Abstract: The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood-brain barrier. The recent identification and characterization of a small population of regulatory T (Treg) cells resident in the brain presents one such potential therapeutic target. Here, we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident Treg cells. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Mice with brain-specific IL-2 delivery were protected in traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients. The work was supported by the VIB, an ERC Consolidator Grant TissueTreg (to A.L.), an ERC Proof of Concept Grant TreatBrainDamage (to A.L.), an ERC Starting Grant AstroFunc (to M.G.H.), an ERC Proof of Concept Grant AD-VIP (to M.G.H.), FWO Research Grant 1513616N (to M.G.H.), Thierry Latran Foundation Grant SOD-VIP (to M.G.H.), an ERNAET Chair (H2020-WIDESPREAD-2018-2020-6; NCBio: 951923; to M.G.H.), FWO Research Grants 1503420N (to E.P.) and 1513020N (to J.W.), an SAO-FRA pilot grant (20190032, to E.P.), and the Biotechnology and Biological Sciences Research Council through Institute Strategic Program Grant funding BBS/E/B/000C0427 and BBS/E/B/000C0428, and the Biotechnology and Biological Sciences Research Council Core Capability Grant to the Babraham Institute. E.P., V.L., M.M., P.G., J.W. and A.d.B. were supported by fellowships from the FWO. R.L. is a senior clinical investigator of FWO Flanders. P.B., O.A. and C.P.F. were supported by an ERA-NET-NEURON grant EJTC 2016 to C.P.F. and by the Netherlands Organization for Scientific research (NWO). The authors acknowledge the important contributions of J. Haughton (VIB) for mouse husbandry, M. Rincon (VIB) for advice on AAV design and production, K. Vennekens for technical support, P. -A. Penttila and the KUL FACS Core, J. Wouters and the KUL Molecular Small Animal Imaging Center (MoSAIC), S. Walker and the Babraham Institute Imaging Core, the VIB Bio-Imaging Core, the VIB Single Cell Sequencing Core, and R. Breedijk, M. Hink and the Leeuwenhoek Center for Advanced Microscopy at the University of Amsterdam.
Published: 2022

39. Pitolisant for Residual Excessive Daytime Sleepiness in OSA Patients Adhering to CPAP

Author: Jean-Louis Pépin, Ognian Georgiev, Rumen Tiholov, Valérie Attali, Johan Verbraecken, Bertien Buyse, Markku Partinen, Ingo Fietze, Georgi Belev, Dejan Dokic, Renaud Tamisier, Patrick Lévy, Isabelle Lecomte, Jeanne-Marie Lecomte, Jean-Charles Schwartz, Yves Dauvilliers, Valerie Attali, Patrice Bourgin, Marie D’Ortho, Frederic Gagnadoux, Jean Claude Meurice, Xuan Lan Nguyen, Katrien Hertegonne, Daniel Rodenstein, Jan Ovesen, Soren Berg, Olli Polo, Tarja Saaresranta, Jan Anders Hedner, Yuksel Peker, W.J. Randerath, Elke Rössner, Diego Garcia Borreguero, Francisco Javier Puertas Cuesta, Joaquim Duran-Cantolla, Ferran Barbe, Dra Odile Romero, Yavor Ivanov, Hristo Metev, Diana Petkova, Merita Ismajli Marku, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, University Hospital Alexandrovska, St. Ivan Rilski University Hospital, Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Antwerp University Hospital [Edegem] (UZA), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Helsinki Sleep Clinic [Helsinki], University of Helsinki, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], St. George Hospital Medical University [Plovidv], University Hospital Center 'Mother Teresa', Bioprojet, Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pitolisant, Population, Excessive daytime sleepiness, Critical Care and Intensive Care Medicine, Placebo, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, OSA, 03 medical and health sciences, chemistry.chemical_compound, residual excessive daytime sleepiness, 0302 clinical medicine, Randomized controlled trial, CPAP, law, medicine, 030212 general & internal medicine, education, pitolisant, education.field_of_study, Intention-to-treat analysis, business.industry, Epworth Sleepiness Scale, respiratory tract diseases, 3. Good health, 030228 respiratory system, Apnea–hypopnea index, chemistry, Physical therapy, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background: Excessive daytime sleepiness (EDS) in individuals with OSA syndrome persisting despite good adherence to CPAP is a disabling condition. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects.Research question: Is pitolisant effective and safe for reducing daytime sleepiness in individuals with moderate to severe OSA adhering to CPAP treatment but experiencing residual EDS?Study design and methods: In a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was titrated individually at up to 20 mg/day and taken over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score in the intention-to-treat population. Key secondary end points were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, Clinical Global Impressions scale of severity, the patient's global opinion, EuroQoL quality-of-life questionnaire score, Pichot fatigue questionnaire score, and safety.Results: Two hundred forty-four OSA participants (82.8% men; mean age, 53.1 years; mean Apnea Hypopnea Index with CPAP, 4.2/h; baseline ESS score, 14.7) were randomized to pitolisant (n = 183) or placebo (n = 61). ESS significantly decreased with pitolisant compared with placebo (-2.6; 95% CI, -3.9 to -1.4; P < .001), and the rate of responders to therapy (ESS ≤ 10 or change in ESS ≥ 3) was significantly higher with pitolisant (71.0% vs 54.1%; P = .013). Adverse event occurrence (mainly headache and insomnia) was higher in the pitolisant group compared with the placebo group (47.0% and 32.8%, respectively; P = .03). No cardiovascular or other significant safety concerns were reported.Interpretation: Pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity.
Published: 2021

40. Impact of subsequent immune checkpoint inhibitor treatment on overall survival with avelumab vs docetaxel in platinum-treated advanced NSCLC: Post hoc analyses from the phase 3 JAVELIN Lung 200 trial

Author: Juliane Manitz, Fabrice Barlesi, Johan Vansteenkiste, Marcis Bajars, Mary Ruisi, Keunchil Park, Mustafa Ozguroglu, James Chih-Hsin Yang, David R. Spigel, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Istanbul University Cerrahpasa, Department of Pulmonology, University Hospitals Leuven [Leuven], Sarah Cannon Research Institute [Nashville, Tennessee], National Taiwan University Cancer Center [Taipei], EMD Serono Research & Development Institute, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)
Subjects: 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, kelch-like ECH associated protein 1, [SDV]Life Sciences [q-bio], medicine.medical_treatment, immune checkpoint inhibitor, Docetaxel, Clinical trial CI, NSCLC, PFS, Avelumab, hazard ratio, 0302 clinical medicine, HR, PD-1, Clinical endpoint, independent review committee, programmed cell death 1 ligand 1, Immune Checkpoint Inhibitors, Lung, education.field_of_study, Hazard ratio, OS, ECOG PS, Eastern Cooperative Oncology Group performance status, 3. Good health, Europe, Clinical trial, serine/threonine kinase 11, IRC, 030220 oncology & carcinogenesis, immunohistochemistry, Immunotherapy, inverse probability of censoring weighting, medicine.drug, PD-L1, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Asia, Ig, EGFR, overall survival, Population, NR, Antibodies, Monoclonal, Humanized, IPCW, programmed cell death 1 protein, 03 medical and health sciences, Internal medicine, medicine, Humans, education, non-small cell lung cancer, Platinum, Phase III as topic, ICI, Programmed cell death 1 ligand 1, business.industry, STK11, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Lung neoplasm, Discontinuation, KEAP1, 030104 developmental biology, confidence interval, epidermal growth factor receptor, not reached, business, immunoglobulin, progression-free survival, IHC
Abstract: Objectives: The JAVELIN Lung 200 phase 3 trial did not meet its primary endpoint of improving overall survival (OS) with avelumab vs docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report post hoc analyses assessing the effects of subsequent immune checkpoint inhibitor (ICI) treatment on OS. Material and methods: Patients with stage IIIB/IV NSCLC progressed following platinum-doublet therapy were randomized to receive avelumab or docetaxel. OS was analyzed in the PD-L1+ population (?1% of tumor cells) and full analysis set (PD-L1+ or PD-L1-). Effects of subsequent ICI (after permanent discontinuation of study treatment) on OS were analyzed using a preplanned naive sensitivity analysis and post hoc inverse probability of censoring weighting (IPCW) analysis. Subgroups with or without subsequent ICI treatment were analyzed using descriptive statistics. Results: In the avelumab and docetaxel arms, a subsequent ICI was received by 16/396 (4.0 %) and 104/396 (26.3 %) after a median of 10.5 months (range, 3.9?20.4) and 5.7 months (range, 0.1?24.4), respectively. Some subgroups showed trends for higher subsequent ICI treatment, including patients with non-squamous NSCLC (avelumab arm, 4.3 % vs docetaxel arm, 32.1 %) or with a baseline ECOG performance status of 0 (6.3 % vs 31.3 %); those enrolled in the early recruitment wave (11.6 % vs 54.3 %), or enrolled in the US/Western Europe (2.8 % vs 45.5 %) or Asia (11.0 % vs 35.4 %); and non-white patients (10.1 % vs 35.0 %). The hazard ratio for OS with avelumab vs docetaxel was lower in the IPCW analysis than in the naive sensitivity analysis (PD-L1+ population: 0.80 [95 % CI, 0.62-1.04] vs 0.86 [95 % CI, 0.68-1.09], respectively). Conclusion: In the JAVELIN Lung 200 trial, avelumab showed clinical activity as second-line treatment for patients with advanced NSCLC. Post hoc analyses suggest that the primary OS analysis may have been confounded by subsequent ICI use in the docetaxel arm. ClinicalTrials.gov identifier: NCT02395172. Merck KGaA, Darmstadt, Germany This work was supported by Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Employees of the sponsor are coauthors of this manuscript, who contributed to the design, execution, and interpretation of the analyses being reported, writing the report, and the decision to submit the article for publication, along with other coauthors
Published: 2021

41. Identifying challenges in neurofibromatosis: a modified Delphi procedure

Author: Marco Nievo, Rianne Oostenbrink, Guenter Heimann, Britt A.E. Dhaenens, Cornelia Potratz, Eric Legius, Scott R. Plotkin, Annette Bakker, D. Gareth Evans, Rosalie E. Ferner, Pierre Wolkenstein, Pediatrics, Erasmus MC other, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Guy's and St Thomas' Hospital [London], University of Manchester [Manchester], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Massachusetts General Hospital [Boston], Novartis Pharma AG, and University Hospitals Leuven [Leuven]
Subjects: medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Delphi Technique, Neurofibromatoses, Patients, [SDV]Life Sciences [q-bio], Health Personnel, Modified delphi, Schwannoma, Article, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Stakeholder Participation, Internal medicine, Genetics, medicine, otorhinolaryngologic diseases, Humans, Neurofibromatosis type 2, Neurofibromatosis, Schwannomatosis, Adaptive clinical trial, Genetics (clinical), High-Grade Glioma, Clinical Trials as Topic, business.industry, Neurodevelopmental disorders, medicine.disease, Research Personnel, 3. Good health, Attitude, 030220 oncology & carcinogenesis, business, 030217 neurology & neurosurgery
Abstract: Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are rare conditions with pronounced variability of clinical expression. We aimed to reach consensus on the most important manifestations meriting the development of drug trials. The five-staged modified Delphi procedure consisted of two questionnaires and a consensus meeting for 40 NF experts, a survey for 63 patient representatives, and a final workshop. In the questionnaires, manifestations were scored on multiple items on a 4-point Likert scale. The highest average scores for NF experts deciding the 'need for new treatment' were for malignant peripheral nerve sheath tumour (MPNST) (4,0) and high grade glioma (HGG) (3,9) for NF1; meningioma (3,9) for NF2 and pain (3,9) for SWN. The patient representatives assigned high scores to all manifestations, with plexiform neurofibroma being highest in NF1 (4,0), vestibular schwannoma in NF2 (4,0), and pain in SWN (3,9). Twelve experts participated in the consensus meeting and prioritised manifestations. MPNST was ranked the highest for NF1, followed by benign peripheral nerve sheath tumours. Tumour manifestations received highest ranking in NF2, and pain was the most prominent problem for SWN. Patient representative ratings for NF1 were similar to the experts' opinions, except that they ranked HGG as the most important manifestation. For NF2 and SWN, the patient representatives agreed with the experts. We conclude that NF experts and patient representatives consent to prioritise development of drug trials for MPNST, benign peripheral nerve sheath tumours, cutaneous manifestations and HGG for NF1; tumours for NF2; and pain for SWN. ispartof: EUROPEAN JOURNAL OF HUMAN GENETICS vol:29 issue:11 pages:1625-1633 ispartof: location:England status: published
Published: 2021

42. The location of DCX mutations predicts malformation severity in X-linked lissencephaly

Author: Perrine Plouin, Pierre-Louis Leger, Hilde Van Esch, Marie Laure Moutard, Fiona Francis, Cherif Beldjord, N Bahi-Buisson, Jean Marc Pinard, Jamel Chelly, Jean Louis Renard, Isabelle Souville, Caroline Elie, Vincent des Portes, Sylvie Joriot, Nathalie Boddaert, Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Réanimation Néonatale et Pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de neurologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], Etude des Civilisations de l'Antiquité ( UMR 7044 ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Université Marc Bloch - Strasbourg II-Centre National de la Recherche Scientifique ( CNRS ), Centre de Référence Maladies Rares ' malformations et maladies congénitales du cervelet ', Hospices Civils de Lyon ( HCL ) -CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Neuropédiatrie, Université de Lyon-CHU de Lyon, Centre for Human Genetics, Katholieke Universiteit Leuven ( KU Leuven ) -University Hospitals Leuven [Leuven], Service de Neuro-pédiatrie[Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Laboratoire de biochimie et génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Etude des Civilisations de l'Antiquité (UMR 7044), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université Marc Bloch - Strasbourg II-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospitals Leuven [Leuven], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Marc Bloch - Strasbourg II-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Adult, Doublecortin Domain Proteins, Male, Doublecortin Protein, Adolescent, Genotype, DNA Mutational Analysis, Mutation, Missense, Lissencephaly, Classical Lissencephalies and Subcortical Band Heterotopias, Biology, medicine.disease_cause, 03 medical and health sciences, Cellular and Molecular Neuroscience, [SCCO]Cognitive science, 0302 clinical medicine, Genetics, medicine, Missense mutation, Humans, Child, Genetics (clinical), X chromosome, 030304 developmental biology, 0303 health sciences, Mutation, Pachygyria, Neuropeptides, Brain, Infant, medicine.disease, Phenotype, Magnetic Resonance Imaging, Doublecortin, Child, Preschool, biology.protein, [ SCCO ] Cognitive science, Microtubule-Associated Proteins, 030217 neurology & neurosurgery
Abstract: International audience; Lissencephaly spectrum (LIS) is one of the most severe neuronal migration disorders that ranges from agyria/pachygyria to subcortical band heterotopia. Approximately 80% of patients with the LIS spectrum carry mutations in either the LIS1 or DCX (doublecortin) genes which have an opposite gradient of severity. The aim of the study was to evaluate in detail the phenotype of DCX-associated lissencephaly and to look for genotype-phenotype correlations. Of the 180 male patients with DCX-related lissencephaly, 33 males (24 familial cases and nine cases with de novo mutations) were found with hemizygous DCX mutations and were clinically and genetically assessed here. DCX mutation analysis revealed that the majority of mutations were missense (79.2%), clustered in the two evolutionary conserved domains, N-DC and C-DC, of DCX. The most prominent radiological phenotype was an anteriorly predominant pachygyria or agyria (54.5%) although DCX-associated lissencephaly encompasses a complete range of LIS grades. The severity of neurological impairment was in accordance with the degree of agyria with severe cognitive impairment in all patients, inability to walk independently in over half and refractory epilepsy in more than a third. For genotype-phenotype correlations, patients were divided in two groups according to the location of DCX missense mutations. Patients with mutations in the C-DC domain tended to have a less severe lissencephaly (grade 4-5 in 58.3%) compared with those in the N-DC domain (grade 4-5 in 36.3%) although, in this dataset, this was not statistically significant (p=0.12). Our evaluation suggests a putative correlation between phenotype and genotype. These data provide further clues to deepen our understanding of the function of the DCX protein and may give new insights into the molecular mechanisms that could influence the consequence of the mutation in the N-DC versus the C-DC domain of DCX.
Published: 2008

43. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

Author: Anna Mayr, Justin L. Garner, Pallav L. Shah, Vincent Ninane, Christophe Pison, Thierry Perez, Bruno Degano, Gaëtan Deslée, Dirk-Jan Slebos, Alexander D. Peterson, Wim Janssens, Jorine E. Hartman, Romain Kessler, Arschang Valipour, Martin Mayse, Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Royal Brompton and Harefield NHS Foundation Trust, Chelsea and Westminster Hospital, Imperial College London, University Medical Center Groningen [Groningen] (UMCG), Université libre de Bruxelles (ULB), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, 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), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Klinik Floridsdorf [Wien], Nuvaira, Inc., Minneapolis, MN, USA, The AIRFLOW-1 clinical trial was funded by Nuvaira, Inc., Minneapolis, MN, USA., Groningen Research Institute for Asthma and COPD (GRIAC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and dormoy, valerian
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Forced Expiratory Volume/physiology, Anticholinergic, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lung/diagnostic imaging, Pulmonary function testing, Pulmonary Disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Quality of life, Double-Blind Method, Chronic Obstructive/diagnosis, Internal medicine, Bronchoscopy, medicine, Humans, COPD, 030212 general & internal medicine, Prospective Studies, Adverse effect, Denervation, lcsh:RC705-779, Lung, business.industry, Nerves, Research, Généralités, lcsh:Diseases of the respiratory system, medicine.disease, Acetylcholine, 3. Good health, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Denervation/methods, Pulmonary Disease, Chronic Obstructive/diagnosis, Quality of Life, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, business, Targeted lung denervation, Follow-Up Studies
Abstract: Following publication of the original article [1], we were notified that the first and last author names have been swapped. The original article has been corrected., SCOPUS: er.j, info:eu-repo/semantics/published
Published: 2021

44. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial

Author: Lore, Vanderbeke, Nico A F, Janssen, Dennis C J J, Bergmans, Marc, Bourgeois, Jochem B, Buil, Yves, Debaveye, Pieter, Depuydt, Simon, Feys, Greet, Hermans, Oscar, Hoiting, Ben, van der Hoven, Cato, Jacobs, Katrien, Lagrou, Virginie, Lemiale, Piet, Lormans, Johan, Maertens, Philippe, Meersseman, Bruno, Mégarbane, Saad, Nseir, Jos A H, van Oers, Marijke, Reynders, Bart J A, Rijnders, Jeroen A, Schouten, Isabel, Spriet, Karin, Thevissen, Arnaud W, Thille, Ruth, Van Daele, Frank L, van de Veerdonk, Paul E, Verweij, Alexander, Wilmer, Roger J M, Brüggemann, Joost, Wauters, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Radboud University Medical Center [Nijmegen], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Ghent University Hospital, Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Elisabeth-TweeSteden Hospital, Erasmus University Rotterdam, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Dutch-Belgian Mycosis Study Group: Bart Rijnders, Paul Verweij, Frank van de Veerdonk, Alexander Schauwvlieghe, Tom Wolfs, Joost Wauters, Katrien Lagrou, Mégarbane, Bruno, Intensive Care, Internal Medicine, MUMC+: MA Medische Staf IC (9), MUMC+: MA Arts Assistenten IC (9), and RS: NUTRIM - R2 - Liver and digestive health
Subjects: AZOLE RESISTANCE, Posaconazole, Original, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Aspergillosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Invasive Pulmonary Aspergillosis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Incidence (epidemiology), Intensive care unit, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, VIRUS, medicine.drug, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Anesthesiology, SURVEILLANCE, Influenza, Human, medicine, Humans, education, FUMIGATUS, business.industry, Prophylaxis, 030208 emergency & critical care medicine, FLUCONAZOLE, Triazoles, medicine.disease, Influenza, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030228 respiratory system, Respiratory failure, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Critical illness
Abstract: Purpose Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA. Methods We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population). Results Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI − 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment. Conclusion The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06431-0.
Published: 2021

45. Natural history of Type 2 and 3 spinal muscular atrophy: 2‐year NatHis‐SMA study

Author: Jean-Yves Hogrel, Myriam Ly-Le Moal, A. Daron, Teresa Gidaro, Timothy Seabrook, Laurent Servais, Carole Vuillerot, Vincent Laugel, Emmanuel Fournier, Pierre G. Carlier, Ulrike Schara, Yann Péréon, Nicole Hellbach, Andreea Mihaela Seferian, Claude Cances, Ksenija Gorni, M. Annoussamy, Linda Lowes, C. Lilien, Ricardo Hermosilla, Christian Czech, Liesbeth De Waele, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), SYSNAV, Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), 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), University Hospitals Leuven [Leuven], KU Leuven Campus Kulak Kortrijk [Belgium], 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], University of Duisburg-Essen, University of Oxford, Nationwide Children's Hospital, Hoffman-La Roche Ltd, Translational Medicine, Neuroscience, Institut ROCHE [Boulogne-Billancourt], Roche S.A.S, Roche Innovation Center [Basel, Switzerland], Pfizer, Gestionnaire, Hal Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), CHU Toulouse [Toulouse], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University of Oxford [Oxford], and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: 0301 basic medicine, Vital capacity, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medizin, MESH: Respiratory Function Tests, NASAL INSPIRATORY PRESSURE, Severity of Illness Index, Pulmonary function testing, MESH: Magnetic Resonance Imaging, Disability Evaluation, 0302 clinical medicine, MESH: Muscular Atrophy, Spinal, MESH: Child, Longitudinal Studies, MESH: Nerve Tissue Proteins, Child, MESH: Longitudinal Studies, Research Articles, VALUES, General Neuroscience, MESH: Muscle Strength, MESH: Disability Evaluation, RNA-Binding Proteins, SMA, Magnetic Resonance Imaging, MESH: Motor Activity, Respiratory Function Tests, medicine.anatomical_structure, MESH: Young Adult, Child, Preschool, Anesthesia, Disease Progression, Upper limb, MESH: Disease Progression, Erratum, Life Sciences & Biomedicine, RC321-571, Research Article, Adult, Adolescent, Clinical Neurology, Neurosciences. Biological psychiatry. Neuropsychiatry, Nerve Tissue Proteins, Motor Activity, Muscular Atrophy, Spinal, Upper Extremity, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, Statistical significance, MESH: Severity of Illness Index, medicine, Humans, Muscle Strength, RC346-429, MESH: Adolescent, Science & Technology, MESH: Humans, business.industry, MESH: Time Factors, MESH: Child, Preschool, Neurosciences, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Survival of motor neuron, MESH: Adult, Spinal muscular atrophy, MESH: Upper Extremity, medicine.disease, 030104 developmental biology, MESH: RNA-Binding Proteins, Neurology. Diseases of the nervous system, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: To characterize the natural history of spinal muscular atrophy (SMA) over 24 months using innovative measures such as wearable devices, and to provide evidence for the sensitivity of these measures to determine their suitability as endpoints in clinical trials. METHODS: Patients with Type 2 and 3 SMA (N = 81) with varied functional abilities (sitters, nonsitters, nonambulant, and ambulant) who were not receiving disease-modifying treatment were assessed over 24 months: motor function (Motor Function Measure [MFM]), upper limb strength (MyoGrip, MyoPinch), upper limb activity (ActiMyo® ), quantitative magnetic resonance imaging (fat fraction [FFT2 ] mapping and contractile cross-sectional area [C-CSA]), pulmonary function (forced vital capacity [FVC], peak cough flow, maximum expiratory pressure, maximum inspiratory pressure, and sniff nasal inspiratory pressure), and survival of motor neuron (SMN) protein levels. RESULTS: MFM32 scores declined significantly over 24 months, but not 12 months. Changes in upper limb activity could be detected over 6 months and continued to decrease significantly over 12 months, but not 24 months. Upper limb strength decreased significantly over 12 and 24 months. FVC declined significantly over 12 months, but not 24 months. FFT2 increased over 12 and 24 months, although not with statistical significance. A significant increase in C-CSA was observed at 12 but not 24 months. Blood SMN protein levels were stable over 12 and 24 months. INTERPRETATION: These data demonstrate that the MFM32, MyoGrip, MyoPinch, and ActiMyo® enable the detection of a significant decline in patients with Type 2 and 3 SMA over 12 or 24 months. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:8 issue:2 pages:359-373 ispartof: location:United States status: published
Published: 2020

46. New remote cerebral microbleeds in acute ischemic stroke: an analysis of the randomized, placebo-controlled WAKE-UP trial

Author: Braemswig, Tim, Vynckier, Jan, Puig, Josep, Thijs, Vincent, Fiebach, Jochen B, Muir, Keith W, Nighoghossian, Norbert, Ebinger, Martin, Pedraza, Salvador, Thomalla, Götz, Gerloff, Christian, Endres, Matthias, Jensen, Märit, Lemmens, Robin, Schlemm, Ludwig, Nolte, Christian, Investigators, WAKE-UP, Boutitie, Florent, Galinovic, Ivana, Simonsen, Claus Z, Cheng, Bastian, Cho, Tae-Hee, Scheitz, Jan F., Fiehler, Jens, CarMeN, laboratoire, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Freie Universität Berlin, OLV Ziekenhuis Aalst Asse Ninove [Aalst, Belgium.], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), Aarhus University Hospital, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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), German Center for Cardiovascular Research (DZHK), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), University of Melbourne, Austin Hospital [Melbourne], Austin Health, University of Glasgow, Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)
Subjects: Science & Technology, Stroke/complications/diagnostic imaging, Clinical Neurology, complications [Brain Ischemia], diagnostic imaging [Cerebral Hemorrhage], Brain Ischemia/complications/diagnostic imaging, Magnetic Resonance Imaging, Brain Ischemia, Cerebral Hemorrhage/complications/diagnostic imaging, Stroke, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Neurology, Ischemic Stroke, diagnostic imaging [Brain Ischemia], complications [Cerebral Hemorrhage], diagnostic imaging [Stroke], Humans, complications [Stroke], Neurosciences & Neurology, ddc:610, Neurology (clinical), Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cerebral Hemorrhage
Abstract: ispartof: JOURNAL OF NEUROLOGY vol:269 issue:10 pages:5660-5667 ispartof: location:Germany status: published
Published: 2022

47. A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor

Author: Maria A. Pantaleo, Michael C. Heinrich, Antoine Italiano, Claudia Valverde, Patrick Schöffski, Giovanni Grignani, Anna K. L. Reyners, Sebastian Bauer, Peter Reichardt, Daniel Stark, Ghimja Berhanu, Ulrike Brandt, Tommaso Stefanelli, Hans Gelderblom, Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Institut Català de la Salut, [Pantaleo MA] Division in Medical Oncology, IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. [Heinrich MC] Portland VA Health Care System and Oregon Health and Science University, Knight Cancer Institute, Portland, Oregon, USA. [Italiano A] Institut Bergonie, Bordeaux, France. [Valverde C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Schöffski P] Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium. [Grignani G] Division of Medical Oncology, Candiolo Cancer Institute, TO, Italy, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Protein Kinase Inhibitors/therapeutic use, Gastrointestinal Stromal Tumors, Medizin, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Alpelisib, Genetics, Sunitinib, Humans, enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal [ENFERMEDADES], neoplasms, Protein Kinase Inhibitors, Aparell digestiu - Càncer - Tractament, Gastrointestinal Stromal Tumors/pathology, Imatinib Mesylate/therapeutic use, Regorafenib, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Thiazoles, Treatment Outcome, Oncology, Imatinib, Avaluació de resultats (Assistència sanitària), Imatinib Mesylate, Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors [DISEASES], Gastrointestinal stromal tumor, GIST
Abstract: Background Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib. Methods This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion. Results Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8–4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%). Conclusions The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing. Trial registration ClinicalTrials.govNCT01735968 (date of initial registration 28/11/2012).
Published: 2022

48. WAO-ARIA consensus on chronic cough – Part III

Author: Philip W. Rouadi, Samar A. Idriss, Jean Bousquet, Tanya M. Laidlaw, Cecilio R. Azar, Mona S. Al-Ahmad, Anahi Yañez, Maryam Ali Y. Al-Nesf, Talal M. Nsouli, Sami L. Bahna, Eliane Abou-Jaoude, Fares H. Zaitoun, Usamah M. Hadi, Peter W. Hellings, Glenis K. Scadding, Peter K. Smith, Mario Morais-Almeida, René Maximiliano Gómez, Sandra N. Gonzalez Diaz, Ludger Klimek, Georges S. Juvelekian, Moussa A. Riachy, Giorgio Walter Canonica, David Peden, Gary W.K. Wong, James Sublett, Jonathan A. Bernstein, Lianglu Wang, Luciana K. Tanno, Manana Chikhladze, Michael Levin, Yoon-Seok Chang, Bryan L. Martin, Luis Caraballo, Adnan Custovic, Jose Antonio Ortego-Martell, Olivia J.Ly Lesslar, Erika Jensen-Jarolim, Motohiro Ebisawa, Alessandro Fiocchi, Ignacio J. Ansotegui, Beirut Eye & ENT Specialist Hospital (BESH), Eye & Ear Hospital [Beirut], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), American University of Beirut Faculty of Medicine and Medical Center (AUB), Middle East Institute of Health, Clemenceau Medical Center (CMC), Kuwait University, Investigaciones en Alergia y Enfermedades Respiratorias (InAER), Hamad Medical Corporation [Doha, Qatar], International Cough Institute (ICI), Louisiana State University (LSU), LAU Medical Center-Rizk Hospital, University Hospitals Leuven [Leuven], Department of Microbiology, Immunology and Transplantation [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Ghent University Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), The Royal National Throat, Nose and Ear Hospital, Griffith University [Brisbane], Hospital CUF Descobertas, Facultad de Ciencias de la Salud [Salta], Universidad Nacional de Salta (UNSA), Universidad Autonoma de Nuevo Leon [Mexique] (UANL), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Saint George Hospital University Medical Center [UOB LIBAN], University of Balamand [Liban] (UOB), Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], UNC School of Medicine, The Chinese University of Hong Kong [Hong Kong], University of Louisville School of Medicine, University of Cincinnati College of Medicine, Peking Union Medical College Hospital [Beijing] (PUMCH), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Akaki Tsereteli State University, University of Cape Town, Seoul National University Bundang Hospital (SNUBH), The Ohio State University Wexner Medical Center., University of Cartagena, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Universidad Autónoma del Estado de Hidalgo (UAEH), LifeSpan medicine, Medizinische Universität Wien = Medical University of Vienna, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University of Vienna [Vienna]-University of Vienna [Vienna]-Medical University Vienna, University of Vienna [Vienna]-University of Vienna [Vienna], Sagamihara National Hospital [Kanagawa, Japan], Bambino Gesù Children’s Hospital [Rome, Italy], Hospital Quirónsalud Bizkaia [Bilbao], and Salvy-Córdoba, Nathalie
Subjects: EXHALED NITRIC-OXIDE, Pulmonary and Respiratory Medicine, Cough specialty care, Chronic cough management, Allergy, AIRWAY INFLAMMATION, Upper airway cough syndrome, Immunology, MUCOSAL EOSINOPHILIC INFLAMMATION, GASTROESOPHAGEAL-REFLUX DISEASE, INHALED CORTICOSTEROIDS, Lower airway disease, Speech therapy, QUALITY-OF-LIFE, CHEST GUIDELINE, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Neuromodulators, VARIANT ASTHMA, Cough primary care, Science & Technology, CLINICAL-PRACTICE GUIDELINE, Reflux cough, REFRACTORY CHRONIC COUGH, Life Sciences & Biomedicine, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: BACKGROUND: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. OBJECTIVES: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. OUTCOMES: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough. ispartof: WORLD ALLERGY ORGANIZATION JOURNAL vol:15 issue:5 ispartof: location:United States status: published
Published: 2022

49. Genome-wide diversity of Zika virus

Author: Sofia G Seabra, Pieter J K Libin, Kristof Theys, Anna Zhukova, Barney I Potter, Hanna Nebenzahl-Guimaraes, Alexander E Gorbalenya, Igor A Sidorov, Victor Pimentel, Marta Pingarilho, Ana T R de Vasconcelos, Simon Dellicour, Ricardo Khouri, Olivier Gascuel, Anne-Mieke Vandamme, Guy Baele, Lize Cuypers, Ana B Abecasis, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Vrije Universiteit Brussel (VUB), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hasselt University (UHasselt), Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Leiden University Medical Center (LUMC), Universiteit Leiden, Lomonosov Moscow State University (MSU), Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Université libre de Bruxelles (ULB), Instituto Gonçalo Moniz / Gonçalo Moniz Research Centre - Fiocruz Bahia [Salvador, Brésil] (IGM), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), University Hospitals Leuven [Leuven], This research was supported in part by the European Union’s Horizon 2020 research and innovation program ZIKAlliance (Agreement No 734548) and by Fundação para a Ciência e Tecnologia (FCT) through funds GHTM-UID/04413/2020. S.G.S. was funded by FCT, Portugal, through contrato-programa 1567 (CEECINST/00102/2018). K.T. was supported by a Fonds Wetenschappelijk Onderzoek post-doctoral grant. P.L. was supported by a doctoral (1S31916N) and post-doctoral grant (#1242021N) provided by the Fonds Wetenschappelijk Onderzoek and was also supported by funding from the Flemish Government under the ‘Onderzoeksprogramma Artificiele Intelligentie (AI) Vlaanderen’ programme. P.L. also received funding from the research council of the Vrije Universiteit Brussel (OZR-VUB) via grant number OZR3863BOF. S.D. acknowledges funding from the Fonds de la Recherche Scientifique (FNRS, Belgium). S.D. and G.B. acknowledge support from the Research Foundation—Flanders (Fonds voor Wetenschappelijk Onderzoek—Vlaanderen, G098321N). B.P. and G.B. acknowledge support from the Internal Fondsen KU Leuven/Internal Funds KU Leuven (Grant No. C14/18/094). G.B. also acknowledges support from the Research Foundation—Flanders (‘Fonds voor Wetenschappelijk Onderzoek—Vlaanderen,’ G0E1420N)., European Project: 734548,ZIKAlliance(2016), and Informatics and Applied Informatics
Subjects: arbovirus, Zika virus, phylogeography, molecular epidemiology, Virology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, evolutionary biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Microbiology
Abstract: International audience; The Zika virus (ZIKV) disease caused a public health emergency of international concern that started in February 2016. The overall number of ZIKV-related cases increased until November 2016, after which it declined sharply. While the evaluation of the potential risk and impact of future arbovirus epidemics remains challenging, intensified surveillance efforts along with a scale-up of ZIKV whole-genome sequencing provide an opportunity to understand the patterns of genetic diversity, evolution, and spread of ZIKV. However, a classification system that reflects the true extent of ZIKV genetic variation is lacking. Our objective was to characterize ZIKV genetic diversity and phylodynamics, identify genomic footprints of differentiation patterns, and propose a dynamic classification system that reflects its divergence levels. We analysed a curated dataset of 762 publicly available sequences spanning the full-length coding region of ZIKV from across its geographical span and collected between 1947 and 2021. The definition of genetic groups was based on comprehensive evolutionary dynamics analyses, which included recombination and phylogenetic analyses, within- and between-group pairwise genetic distances comparison, detection of selective pressure, and clustering analyses. Evidence for potential recombination events was detected in a few sequences. However, we argue that these events are likely due to sequencing errors as proposed in previous studies. There was evidence of strong purifying selection, widespread across the genome, as also detected for other arboviruses. A total of 50 sites showed evidence of positive selection, and for a few of these sites, there was amino acid (AA) differentiation between genetic clusters. Two main genetic clusters were defined, ZA and ZB, which correspond to the already characterized ‘African’ and ‘Asian’ genotypes, respectively. Within ZB, two subgroups, ZB.1 and ZB.2, represent the Asiatic and the American (and Oceania) lineages, respectively. ZB.1 is further subdivided into ZB.1.0 (a basal Malaysia sequence sampled in the 1960s and a recent Indian sequence), ZB.1.1 (South-Eastern Asia, Southern Asia, and Micronesia sequences), and ZB.1.2 (very similar sequences from the outbreak in Singapore). ZB.2 is subdivided into ZB.2.0 (basal American sequences and the sequences from French Polynesia, the putative origin of South America introduction), ZB.2.1 (Central America), and ZB.2.2 (Caribbean and North America). This classification system does not use geographical references and is flexible to accommodate potential future lineages. It will be a helpful tool for studies that involve analyses of ZIKV genomic variation and its association with pathogenicity and serve as a starting point for the public health surveillance and response to on-going and future epidemics and to outbreaks that lead to the emergence of new variants.The Zika virus (ZIKV) disease caused a public health emergency of international concern that started in February 2016. The overall number of ZIKV-related cases increased until November 2016, after which it declined sharply. While the evaluation of the potential risk and impact of future arbovirus epidemics remains challenging, intensified surveillance efforts along with a scale-up of ZIKV whole-genome sequencing provide an opportunity to understand the patterns of genetic diversity, evolution, and spread of ZIKV. However, a classification system that reflects the true extent of ZIKV genetic variation is lacking. Our objective was to characterize ZIKV genetic diversity and phylodynamics, identify genomic footprints of differentiation patterns, and propose a dynamic classification system that reflects its divergence levels. We analysed a curated dataset of 762 publicly available sequences spanning the full-length coding region of ZIKV from across its geographical span and collected between 1947 and 2021. The definition of genetic groups was based on comprehensive evolutionary dynamics analyses, which included recombination and phylogenetic analyses, within- and between-group pairwise genetic distances comparison, detection of selective pressure, and clustering analyses. Evidence for potential recombination events was detected in a few sequences. However, we argue that these events are likely due to sequencing errors as proposed in previous studies. There was evidence of strong purifying selection, widespread across the genome, as also detected for other arboviruses. A total of 50 sites showed evidence of positive selection, and for a few of these sites, there was amino acid (AA) differentiation between genetic clusters. Two main genetic clusters were defined, ZA and ZB, which correspond to the already characterized ‘African’ and ‘Asian’ genotypes, respectively. Within ZB, two subgroups, ZB.1 and ZB.2, represent the Asiatic and the American (and Oceania) lineages, respectively. ZB.1 is further subdivided into ZB.1.0 (a basal Malaysia sequence sampled in the 1960s and a recent Indian sequence), ZB.1.1 (South-Eastern Asia, Southern Asia, and Micronesia sequences), and ZB.1.2 (very similar sequences from the outbreak in Singapore). ZB.2 is subdivided into ZB.2.0 (basal American sequences and the sequences from French Polynesia, the putative origin of South America introduction), ZB.2.1 (Central America), and ZB.2.2 (Caribbean and North America). This classification system does not use geographical references and is flexible to accommodate potential future lineages. It will be a helpful tool for studies that involve analyses of ZIKV genomic variation and its association with pathogenicity and serve as a starting point for the public health surveillance and response to on-going and future epidemics and to outbreaks that lead to the emergence of new variants.
Published: 2022

50. Molecular Heterogeneity Between Paired Primary and Metastatic Lesions from Clear Cell Renal Cell Carcinoma

Author: Eduard Roussel, Lisa Kinget, Annelies Verbiest, Jessica Zucman-Rossi, Bram Boeckx, Steven Joniau, Diether Lambrechts, Maarten Albersen, Benoit Beuselinck, Zucman-Rossi, Jessica, University Hospitals Leuven [Leuven], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)
Subjects: Molecular subtypes, Urology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Heterogeneity, Metastases, Clear cell, Renal cell carcinoma, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: UNLABELLED: Highly effective systemic treatments have globally improved outcomes in metastatic clear-cell renal cell carcinoma (m-ccRCC). However, despite many efforts, reliable biomarkers predicting individual responses are currently lacking. Moreover, mixed responses are commonly observed. We hypothesized that molecular heterogeneity between primary tumors and their metastases could flaw biomarker research based on features of the primary tumor and explain mixed responses. Therefore, we studied the heterogeneity of the ccrcc1-4 molecular subtypes across patient-matched primary and metastatic lesions over time in 62 patients with m-ccRCC who underwent both nephrectomy and metastasectomy. These subtypes characterize underlying disease biology and are associated with outcomes in both the primary and metastatic settings. We observed a concordance rate of 58% (95% confidence interval 45-71%). This concordance was not affected by the interval between nephrectomy and resection of the metastatic lesion. Across discordant pairs, the metastatic lesions mostly exhibited a less favorable molecular subtype. Moreover, primary tumors with the favorable ccrcc2 molecular subtype were characterized by favorable prognosis and a long interval between nephrectomy and metastasectomy. Conversely, tumors with the unfavorable ccrcc4 molecular subtype relapsed quickly and had poor prognosis. Thus, the considerable molecular heterogeneity between patient-matched m-ccRCC primary and metastatic lesions provides an explanation for mixed responses to systemic therapy and could impact the development of biomarker studies in which the primary tumor is often considered a surrogate for metastatic disease. PATIENT SUMMARY: We studied primary tumors and metastases from patients with kidney cancer and found considerable heterogeneity in their molecular features. This heterogeneity explains mixed responses to systemic therapy and is important to take into account in future biomarker studies for this disease. ispartof: EUROPEAN UROLOGY OPEN SCIENCE vol:40 pages:54-57 ispartof: location:Netherlands status: published
Published: 2022

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