4,703 results on '"The Royal Melbourne Hospital"'
Search Results
2. Early Oral Step-down Antibiotic Therapy for Uncomplicated Gram-negative Bacteraemia
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Singapore Clinical Research Institute, Singapore, National University Hospital, Singapore, Singapore General Hospital, Changi General Hospital, Ng Teng Fong General Hospital, Singapore, Sengkang General Hospital, Singapore, Royal Brisbane and Women's Hospital, Australia, Royal Melbourne Hospital, Australia, University Malaya Medical Centre, Malaysia, Samsung Medical Center, South Korea, Princess Alexandra Hospital, Australia, Gold Coast University Hospital, Australia, Ampang Hospital, Malaysia, Sungai Buloh Hospital, Malaysia, Universiti Kebangsaan Medical Centre, Malaysia, Medipol Mega University Hospital, Turkey, Rambam Hospital, Israel, Sheba Medical Centre, Israel, IRCCS Policlinico di Sant'Orsola, University Alma Mater Studiorum of Bologna, Italy, Monaldi Hospital, Italy, University Hospital of Pisa, Italy, IRCCS San Raffaele Hospital, Milan, Italy, University General Hospital of Patras, Greece, Hospital del Mar, Parc de Salut MAR, Spain, and American University of Beirut Medical Center, Lebanon
- Published
- 2023
3. The Effect of Prophylactic Pre Operative Probiotic Therapy on Endotoxin Levels in Cardiac Surgery Patients
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Intensive Care Unit Research Department, Royal Melbourne Hospital
- Published
- 2015
4. Not all roads lead to the immune system: the genetic basis of multiple sclerosis severity
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Multiple Sclerosis Research Australia, Royal Melbourne Hospital, Multiple Sclerosis Society (UK), MSBase Foundation, Monash University, Jokubaitis, Vilija G., Campagna, Maria Pia, Ibrahim, Omar A., Stankovich, JIm, Kleinova, Pavlina, Matesanz, Fuencisla, Hui, Daniel, Eichau, Sara, Slee, Mark, Lechner-Scott, Jeannette, Lea, Rodney, Kilpatrick, Trevor J., Kalincik, Tomas, De Jager, Philip L., Beecham, Ashley, McCauley, Jacob L., Taylor, Bruce V., Vucic, Steve, Laverick, Louise, Vodehnalova, Karolina, García-Sánchez, María Isabel, Alcina, Antonio, van der Walt, Anneke, Kubala Havrdova, Eva, Izquierdo, Guillermo, Patsopoulos, Nikolaos, Horakova, Dana, Butzkueven, Helmut, Multiple Sclerosis Research Australia, Royal Melbourne Hospital, Multiple Sclerosis Society (UK), MSBase Foundation, Monash University, Jokubaitis, Vilija G., Campagna, Maria Pia, Ibrahim, Omar A., Stankovich, JIm, Kleinova, Pavlina, Matesanz, Fuencisla, Hui, Daniel, Eichau, Sara, Slee, Mark, Lechner-Scott, Jeannette, Lea, Rodney, Kilpatrick, Trevor J., Kalincik, Tomas, De Jager, Philip L., Beecham, Ashley, McCauley, Jacob L., Taylor, Bruce V., Vucic, Steve, Laverick, Louise, Vodehnalova, Karolina, García-Sánchez, María Isabel, Alcina, Antonio, van der Walt, Anneke, Kubala Havrdova, Eva, Izquierdo, Guillermo, Patsopoulos, Nikolaos, Horakova, Dana, and Butzkueven, Helmut
- Abstract
Multiple sclerosis is a leading cause of neurological disability in adults. Heterogeneity in multiple sclerosis clinical presentation has posed a major challenge for identifying genetic variants associated with disease outcomes. To overcome this challenge, we used prospectively ascertained clinical outcomes data from the largest international multiple sclerosis registry, MSBase. We assembled a cohort of deeply phenotyped individuals of European ancestry with relapse-onset multiple sclerosis. We used unbiased genome-wide association study and machine learning approaches to assess the genetic contribution to longitudinally defined multiple sclerosis severity phenotypes in 1813 individuals. Our primary analyses did not identify any genetic variants of moderate to large effect sizes that met genome-wide significance thresholds. The strongest signal was associated with rs7289446 (ß = ¿0.4882, P = 2.73 × 10¿7), intronic to SEZ6L on chromosome 22. However, we demonstrate that clinical outcomes in relapse-onset multiple sclerosis are associated with multiple genetic loci of small effect sizes. Using a machine learning approach incorporating over 62 000 variants together with clinical and demographic variables available at multiple sclerosis disease onset, we could predict severity with an area under the receiver operator curve of 0.84 (95% CI 0.79¿0.88). Our machine learning algorithm achieved positive predictive value for outcome assignation of 80% and negative predictive value of 88%. This outperformed our machine learning algorithm that contained clinical and demographic variables alone (area under the receiver operator curve 0.54, 95% CI 0.48¿0.60). Secondary, sex-stratified analyses identified two genetic loci that met genome-wide significance thresholds. One in females (rs10967273; ßfemale = 0.8289, P = 3.52 × 10¿8), the other in males (rs698805; ßmale = ¿1.5395, P = 4.35 × 10¿8), providing some evidence for sex dimorphism in multiple sclerosis severity. Tissue enrich
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- 2023
5. Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome. An international observational study
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Verboon, C., Harbo, T., Cornblath, D. R., Hughes, R. A. C., Van Doorn, P. A., Lunn, M. P., Gorson, K. C., Barroso, F., Kuwabara, S., Galassi, G., Lehmann, H. C., Kusunoki, S., Reisin, R. C., Binda, D., Cavaletti, G., Andersen, Jacobs B. C. H., PhD (Aarhus University Hospital, Aarhus, Denmark), Attarian, S., PhD (CHU Timone, Marseille, France), Badrising, U. A., PhD (Leiden University Medical Centre, Leiden, The, Netherlands), Bateman, K., PhD (Groote Schuur Hospital, Cape, Town, South-Africa), Benedetti, L., PhD (Ospedale Sant’ Andrea La Spezia, Spezia, La, Italy), van den Berg, B., MD (Franciscus Gasthuis, Rotterdam, Van den Bergh, P., Luc, PhD (University Clinic St., Leuven, Belgium), Bertorini, T. E., MD (The University of Tennessee Health Science Center (UTHSC), Memphis, USA), Bhavaraju-Sanka, R., MD (University Hospital/ University of Texas Health Science Center, San Antonio Texas, USA), Bianco (Milan University, M., Humanitas Clinicala and Research Institute Milan, Briani, C., MD (University of Padova, Padova, Italy), Bürmann, J., MD (Universitätsklinikum des Saarlandes, Homburg, Germany), Casasnovas, C., Ciberer, PhD (Bellvitge University Hospital - IDIBELL Neurometabolic Diseases Group., Barcelona, Spain), Chao, C. C., PhD (National Taiwan University Hospital, Taipei, Taiwan), Chavada, G., PhD (Glasgow University, Glasgow, UK), Claeys, K. G., University Hospitals Leuven, PhD (1., Leuven, Belgium, KU Leuven, 2., Cosgrove, J. S., MD (Leeds General Infirmary, Leeds, UK), Dalakas, M. C., Thomas Jefferson University, MD (1., Philadelphia, Usa, National and Kapodistrian University of Athens, 2., Athens, Greece), Davidson, A., MD (University of Glasgow, van Dijk, G. W., MD (Canisius Wilhelmina Hospital, Nijmegen, Dardiotis, E., MD (University of Thessaly, Hospital of Larissa, Larissa, Greece), Derejko, M., MD (Odense University Hospital, Odense, Denmark), Dimachkie, M. M., MD (University of Kansas Medical Center, Kansas, City, Dornonville de la Cour, C., MD (National Hospital Copenhagen, Copenhagen, Denmark), Echaniz-Laguna, A., MD (Bicêtre University Hospital, Paris, France), Eftimov, F., PhD (Amsterdam University Medical Centre, Amsterdam, Faber, C. G., PhD (Maastricht University Medical Centre, Maastricht, Fazio, R., MD (Scientific Institute San Raffaele, Milan, Italy), Fulgenzi, J. Fehmi (University of Oxford E. A., MD (Hospital Cesar Milstein Buenos Aires, Buenos, Aires, Argentina), García-Sobrino, T., MD (Hospital Clínico de Santiago, Santiago de Compostela (A Coruña), Spain), Gijsbers, C. J., MD (Vlietland Hospital, Schiedam, Granit, V., MD (Montefiore Medical, Center, New, York, Grisanti, S., MD (Ospedale Sant’ Andrea La Spezia, Gutiérrez-Gutiérrez, G., MD (Hospital Universitario Infanta Sofia, San, Sebastian, Holbech, J. V., PhD (Odense University Hospital, Holt, J. K. L., Phd, FRCP (The Walton Centre, Liverpool, UK), Homedes, C., Ciberer, MD (Bellvitge University Hospital - IDIBELL Neurometabolic Diseases Group., Islam, B., PhD (International Centre for Diarrhoeal Disease Research, Bangladesh, (icddr, Dhaka, b), Bangladesh), Islam, Z., Jahan, I., PhD candidate (International Centre for Diarrhoeal Disease Research, Jericó Pascual, I., PhD (Complejo Hospitalario de Navarra, Pamplona, Spain), Karafiath, S., MD (University of Utah School of Medicine, Salt Lake City, Kerkhoff, H., PhD (Albert Schweitzer Hospital, Dordrecht, Kimpinski, K., MD (University Hospital, Lhsc, London-Ontario, Canada), Kohler, A., MD (Instituto de Investigaciones Neurológicas Raúl Carrea, Fleni, Kolb, N., MD (University of Vermont, Burlington, Vt, Kuitwaard, K., Albert Schweitzer Hospital, PhD (1., Erasmus MC, 2., Kuwahara, M., PhD (Kindai University, Osaka, Japan), Ladha, S. S., MD (Barrow Neurology Clinics, Phoenix, Arizona, Lee Pan, E., MBChB (Groote Schuur Hospital, Marfia, G. A., MD (Neurological Clinic, Policlinico Tor Vergata, Rome, Italy), Magot, A., MD (Reference Centre for NMD, Nantes University Hospital, France), Márquez Infante, C., MD (Hospital Universitario Virgen del Rocio, Seville, Spain), Martín-Aguilar, L., MD (Hospital de la Santa Creu, i Sant Pau, Universitat Autònoma de Barcelona, Martinez Hernandez, E., MD (Institut d’Investigacions Biomèdiques August Pi, i Sunyer (IDIBAPS), Hospital, Clinic, Mataluni, G., PhD (Neurological Clinic, Meekins, G., MD (University of Minnesota, Miller, J. A. L., PhD (Royal Victoria Infirmary, Newcastle, UK), Monges, M. S., Garrahan, MD (Hospital de Pediatría J. P., Nobile Orazio, E., PhD (Milan University, Pardal, A., MD (Hospital Britanico, Pardo Fernandez (Hospital Clínico de Santiago, J., Péréon, Y., PhD (Reference Centre for NMD, Pulley, M., MD (University of Florida, Jacksonville, USA), Querol Gutierrez, L., PhD (Hospital de la Santa Creu, i Sant Pau, Reddel, S. W., PhD (Concord Repatriation General Hospital, Sydney, Australia), van der Ree, T., (Westfriesgasthuis, Md, Hoorn, Rinaldi, S., Mbchb, Samijn, PhD (University of Oxford J. P. A., MD (Maasstad Hospital, Samukawa, M., Santoro, L., PhD (University Federico II, Napels, Italy), Savransky, A., Garrahan, PhD (Hospital de Pediatría J. P., Schwindling, L., Sedano Tous, M. J., MD (Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Sekiguchi, Y., PhD (Chiba University, Chiba, Japan), Shahrizaila, N., MD (Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaya), Silvestri, N. J., Sindrup, MD (Buffalo Jacobs School of Medicine S., Sommer, C. L., MD (Universitätsklinikum Würzburg, Würzburg, Germany), Spyropoulos (Royal Victoria Infirmary, A., Stein, B., Joseph’s Regional Medical Center, MD (St., Paterson, USA), Tan, C. Y., MRCP (Neurology Unit, Tankisi, H., Vermeij, F., Vytopil, M. V., Wirtz, PhD (Tufts University School of Medicine Lahey Hospital P. W., Phd, (HagaZiekenhuis, The, Hague, Waheed, W., MD (University of Vermont Medical Center, Burlington, Addington, USA). Other collaborators were:J. M., MD (University of Virginia, Charlottesville, USA), Ajroud-Driss, S., MD (Northwestern University Feinberg, Chicago, USA), Antonini, G., MD (Mental Health and Sensory Organs (NESMOS), Sapienza, University, Sant’Andrea, Hospital, Bella, I. R., MD (University of Mass Medical School, Worcester, USA), Brannagan, T. H., MD (Columbia University, New York City, Bunschoten, C., PhD candidate (Erasmus University Medical Centre, Busby, M., Bradford, UK), Butterworth, S., MD (Pinderfields Hospital, Wakefield, UK), Conti, M. E., MD (University Hospital Clinicas, Chen, S., Phd, (Rutgers, Robert Wood Johnson University Hospital, New, Brunswick, Doets, A., Feasby, T. E., MD (University of Calgary, Calgary, Canada), Fokke, C., MD (Gelre Hospital, Zutphen and Apeldoorn, Fujioka, T., MD (Toho University Medical Center, Tokyo, Japan), Garssen, M. P. J., PhD (Jeroen Bosch Hospital, Hertogenbosch, ’S, Gilchrist, J. M., MD (Soulthern Illinois University School of Medicine, Springfield, USA), Gilhuis, J., PhD (Reinier de Graaf Gasthuis, Delft, Goldstein, J. M., MD (Yale University School of Medicine, New, Haven, Goyal, N. A., MD (University of California, Irvine, USA), Hadden, R. D. M., PhD (King’s College Hospital, London, UK), Hsieh, S. T., Htut, M., George’s Hospital, MD (St., Illa, I., Jellema, K., PhD (Haaglanden Medisch Centrum, Kaida, K., PhD (National Defense Medical College, Saitama, Japan), Katzberg, H. D., MD (University of Toronto, Toronto, Canada), Kiers, L., MD (University of Melbourne, Royal Melbourne Hospital, Parkville, Australia), Kokubun, N., MD (Dokkyo Medical University, Tochigi, Japan), van Koningsveld, R., PhD (Elkerliek Hospital, Helmond and Deurne, van der Kooi, A. J., Kwan, J. Y., MD (University of Maryland School of Medicine, Baltimore, USA), Landschoff Lassen, L., MD (Glostrup Hospital, Glostrup, Denmark), Lawson, V., MD (Wexner Medical Center at The Ohio State University, Columbus, USA), Leonhard, S. E., Mandarakas, M., PhD (Erasmus University Medical Centre, Manji, H., FRCP (Ipswich Hospital, Ipswich, UK), Mattiazzi, M. G., MD (Hospital Militar Central, Mcdermott, C. J., MD (Royal Hallamshire Hospital, Nihr, Clinical, Sheffield, UK), Mohammad, Q. D., PhD (National Institute of Neurosciences and Hospital, Dhaka, Bangladesh), Morís de la Tassa, G., MD (Hospital UniversitarioCentral de Asturias, Asturias, Spain), Nascimbene, C., PhD (Luigi Sacco Hospital, Niks, E. H., Nowak, R. J., Osei-Bonsu, M., PhD (James Cook University Hospital, Middlesbrough, UK), Pascuzzi, R. M., MD (University of Indiana School of Medicine, Indianapolis, USA), Roberts, R. C., MD (Addenbrooke’s Hospital Cambridge, Cambridge, UK), Rojas-Marcos, I., MD (Hospital Univesitario Reina Sofia, Cordoba, Spain), Roodbol, J., Rudnicki, S. A., MD (University of Arkansas, Fayetteville, USA), Sachs, G. M., MD (University of Rhode Island, Providence, USA), Schenone, A., Department of Neurosciences, PhD (1., Rehabilitation, Ophthalmology, Genetics and Maternal and Infantile Sciences (DINOGMI), University of Genova, Genova, IRCCS Policlinico San Martino, Italy 2., Genova, Italy), Sheikh, K., PhD (The University of Texas Health Science Center at Houston, Houston, USA), Twydell, P., DO (Spectrum Health System, Grand, Rapids, Van Damme, P., PhD (University Hospital Leuven, Varrato, J. D., DO (Lehigh Valley Health Network, Allentown, USA), Visser, L. H., PhD (Elisabeth-TweeSteden Hospital, Tilburg and Waalwijk, Willison, H. J., PhD (University of Glasgow, van Woerkom (Erasmus MC, M., Zhou, L., PhD (Icahn School, Verboon, C, Harbo, T, Cornblath, D, Hughes, R, Van Doorn, P, Lunn, M, Gorson, K, Barroso, F, Kuwabara, S, Galassi, G, Lehmann, H, Kusunoki, S, Reisin, R, Binda, D, Cavaletti, G, Jacobs, B, consortium, IGOS, consortium, GOS, Neurosurgery, Neurology, and Immunology
- Subjects
Adult ,Male ,medicine.medical_specialty ,intravenous immunoglobulins ,DIAGNOSIS ,Guillain-Barre Syndrome ,Settore MED/26 ,DISEASE ,Disease course ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,hemic and lymphatic diseases ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,In patient ,guillain-barré syndrome ,030212 general & internal medicine ,NEUROPATHIES ,biology ,Guillain-Barre syndrome ,business.industry ,Guillain-Barré syndrome (GBS), treatment, course ,Confounding ,Immunoglobulins, Intravenous ,Middle Aged ,medicine.disease ,Confidence interval ,Psychiatry and Mental health ,Treatment Outcome ,biology.protein ,Female ,Surgery ,Observational study ,Neurology (clinical) ,Antibody ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.MethodsWe selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.ResultsOf 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.ConclusionIn patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.
- Published
- 2021
6. Second IVIg course in Guillain-Barré syndrome with poor prognosis. The non-randomised ISID study
- Author
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Verboon, C., Van Den Berg, B., Cornblath, D. R., Venema, E., Gorson, K. C., Lunn, M. P., Lingsma, H., Van Den Bergh, P., Harbo, T., Bateman, K., Pereon, Y., Sindrup, So. H., Kusunoki, S., Miller, J., Islam, Z., Hartung, H. -P., Chavada, G., Jacobs, B. C., Hughes, R. A. C., Addington, Van Doorn P. A. J. M., MD (University of Virginia, Charlottesville, USA), on October 7, S. Consortia. Protected by copyright., Downloaded from 8 Verboon C, 2019 at Uppsala Universitet BIBSAM http://jnnp. bmj. com/ J Neurol Neurosurg Psychiatry: first published as 10. 1136/jnnp-2019-321496 on 5 October 2019., J Neurol Neurosurg Psychiatry 2019, et al., 1136/jnnp-2019-321496 Neuromuscular Ajroud-Driss, 0:1–9. doi:10., MD (Northwestern University Feinberg, Chicago, USA), Antonini, G., MD (Mental Health and Sensory Organs (NESMOS), Sapienza, University, Sant’Andrea, Hospital, Rome, Italy), Attarian, S., PhD (CHU Timone, Marseille, France), Barroso, F. A., MD (Instituto de Investigaciones Neurológicas Raúl Carrea, Fleni, Buenos, Aires, Argentina), Benedetti, L., PhD (Ospedale Sant’ Andrea La Spezia, Spezia, La, Italy), Bertorini, T. E., MD (The University of Tennessee Health Science Center (UTHSC), Memphis, USA), Brannagan, T. H., MD (Columbia University, New York City, USA), Briani, C., MD (University of Padova, Padova, Italy), Bhavaraju-Sanka, R., MD (University Hospital/University of Texas Health Science Center, San Antonio Texas, Butterworth, S., MD (Pinderfields Hospital, Wakefield, UK), Casasnovas, C., Ciberer, PhD (Bellvitge University Hospital – IDIBELL Neurometabolic Diseases Group., Barcelona, Spain), Cavaletti, G., MD (University Milano-Bicocca, Monza, Italy), Chen, S., Phd, (Rutgers, Robert Wood Johnson University Hospital, New, Brunswick, Claeys, K. G., University Hospitals Leuven, PhD (1., Leuven, Belgium, KU Leuven, 2., Leuven, Belgium), Cosgrove, J. S., MD (Leeds General Infirmary, Leeds, UK), Davidson, A., MD (University of Glasgow, Glasgow, UK), Dardiotis, E., MD (University of Thessaly, Hospital of Larissa, Larissa, Greece), Dornonville de la Cour, C., MD (National Hospital Copenhagen, Copenhagen, Denmark), Faber, C. G., PhD (Maastricht University Medical Centre, Maastricht, The, Netherlands), Feasby, T. E., MD (University of Calgary, Calgary, Canada), Fujioka, T., MD (Toho University Medical Center, Tokyo, Japan), Galassi, G., MD (University Hospital of Modena, Modena, Italy), Gilchrist, J. M., MD (Soulthern Illinois University School of Medicine, Springfield, USA), Goyal, N. A., MD (University of California, Irvine, USA), Granit, V., MD (Montefiore Medical, Center, New, York, Gutiérrez-Gutiérrez, G., MD (Hospital Universitario Infanta Sofia, San, Sebastian, Spain), Hadden, R. D. M., PhD (King’s College Hospital, London, UK), Holt, J. K. L., Phd, FRCP (The Walton Centre, Liverpool, UK), Htut, M., George’s Hospital, MD (St., Jericó Pascual, I., PhD (Complejo Hospitalario de Navarra, Pamplona, Spain), Karafiath, S., MD (University of Utah School of Medicine, Salt Lake City, Katzberg, H. D., MD (University of Toronto, Toronto, Canada), Kiers, L., MD (University of Melbourne, Royal Melbourne Hospital, Parkville, Australia), Kieseier, B. C., MD (Heinrich Heine University, Düsseldorf, Germany), Kimpinski, K., MD (University Hospital, Lhsc, London-Ontario, Canada), Kuwabara, S., PhD (Chiba University, Chiba, Japan), Kwan, J. Y., MD (University of Maryland School of Medicine, Baltimore, USA), Ladha, S. S., MD (Barrow Neurology Clinics, Phoenix, Arizona, Lawson, V., MD (Wexner Medical Center at The Ohio State University, Columbus, USA), Lehmann, H., PhD (University Hospital of Cologne, Universitätsklinikum, Köln, Cologne, Germany), Manji, H., FRCP (Ipswich Hospital, Ipswich, UK), Marfia, G. A., MD (Neurological Clinic, Policlinico Tor Vergata, Márquez Infante, C., MD (Hospital Universitario Virgen del Rocio, Seville, Spain), Mattiazzi, M. G., MD (Hospital Militar Central, Mcdermott, C. J., MD (Royal Hallamshire Hospital, Nihr, Clinical, Sheffield, UK), Monges, M. S., Garrahan, MD (Hospital de Pediatría J. P., Morís de la Tassa, G., MD (Hospital Universitario Central de Asturias, Asturias, Spain), Nascimbene, C., PhD (Luigi Sacco Hospital, Milan, Italy), Nobile Orazio, E., PhD (Milan University, Humanitas Clinicala and Research Institute Milan, Nowak, R. J., MD (Yale University School of Medicine, New, Haven, Osei-Bonsu (James Cook University Hospital, M., Middlesbrough, UK), Pardo Fernandez (Hospital Clínico de Santiago, J., Santiago de Compostela (A Coruña), Querol Gutierrez, L., PhD (Hospital de la Santa Creu, i Sant Pau, Universitat Autònoma de Barcelona, Reisin (Hospital Britanico, R., Rinaldi, S., Mbchb, Roberts, PhD (University of Oxford R. C., MD (Addenbrooke’s Hospital Cambridge, Cambridge, UK), Rojas-Marcos, I., MD (Hospital Univesitario Reina Sofia, Cordoba, Spain), Rudnicki, S. A., MD (University of Arkansas, Fayetteville, USA), Schenone, A., Department of Neurosciences, PhD (1., Rehabilitation, Ophthalmology, Genetics and Maternal and Infantile Sciences (DINOGMI), University of Genova, Genova, IRCCS Policlinico San Martino, Italy 2., Genova, Italy), Sedano Tous, M. J., MD (Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Shahrizaila, N., MD (Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaya), Sheikh, K., PhD (The University of Texas Health Science Center at Houston, Houston, USA), Silvestri, N. J., MD (Buffalo General Medical Center, Buffalo, Ny, Sommer, C. L., MD (Universitätsklinikum Würzburg, Würzburg, Germany), Varrato, J. D., DO (Lehigh Valley Health Network, Allentown, USA), Verschuuren, J., PhD (Leiden University Medical Centre, Leiden, Vytopil, M. V., Waheed, PhD (Tufts University School of Medicine Lahey Hospital W., MD (University of Vermont Medical Center, Burlington, USA), Zhou, L., PhD (Icahn School of Medicine at Mount Sinai, Badrising, USA). Other collaborators were:U. A., Bella, I. R., MD (University of Mass Medical School, Worcester, USA), Bunschoten, C., PhD candidate (Erasmus University Medical Centre, Rotterdam, Bürmann, J., Universitätsklinikum des Saarlandes, Homburg, Germany), Busby, M., Bradford, UK), Chao, C. C., PhD (National Taiwan University Hospital, Taipei, Taiwan), Conti, M. E., MD (University Hospital Clinicas, Dalakas, M. C., Thomas Jefferson University, MD (1., Philadelphia, Usa, National and Kapodistrian University of Athens, 2., Athens, Greece), Van Damme, P., PhD (University Hospital Leuven, Doets, A., van Dijk, G. W., MD (Canisius Wilhelmina Hospital, Nijmegen, Dimachkie, M. M., MD (University of Kansas Medical Center, Kansas, City, Doppler, K., Echaniz-Laguna, A., MD (Hopital de Hautepierre, Strasbourgh, France), Eftimov, F., PhD (Amsterdam University Medical Centre, Amsterdam, Fazio, R., MD (Scientific Institute San Raffaele, Fokke, C., MD (Gelre Hospital, Zutphen and Apeldoorn, Fulgenzi, E. A., MD (Hospital Cesar Milstein Buenos Aires, Garssen, M. P. J., PhD (Jeroen Bosch Hospital, Hertogenbosch, ’S, Zaltbommel and Drunen, Gijsbers, C. J., MD (Vlietland Hospital, Schiedam, Gilhuis, J., PhD (Reinier de Graaf Gasthuis, Delft, Grapperon, A., MD (CHU Timone, Hsieh, S. T., Illa, I., Islam, B., PhD (International Centre for Diarrhoeal Disease Research, Bangladesh, (icddr, Dhaka, b), Bangladesh), Jellema, K., PhD (Haaglanden Medisch Centrum, The, Hague, Kaida, K., PhD (National Defense Medical College, Saitama, Japan), Kokubun, N., MD (Dokkyo Medical University, Tochigi, Japan), Kolb, N., MD (University of Vermont, Burlington, Vt, van Koningsveld, R., PhD (Elkerliek Hospital, Helmond and Deurne, van der Kooi, A. J., Kuitwaard, K., PhD (Albert Schweitzer Hospital, Dordrecht, Landschoff Lassen, L., MD (Glostrup Hospital, Glostrup, Denmark), Leonhard, S. E., Mandarakas, M., PhD (Erasmus University Medical Centre, Martinez Hernandez, E., MD (Institut d’Investigacions Biomèdiques August Pi, i Sunyer (IDIBAPS), Hospital, Clinic, Mohammad, Q. D., PhD (National Institute of Neurosciences and Hospital, Dhaka, Bangladesh), Pulley, M., MD (University of Florida, Jacksonville, USA), Rajabally, Y. A., PhD (Queen Elizabeth Hospital, Birmingham, UK), Reddel, S. W., PhD (Concord Repatriation General Hospital, Sydney, Australia), van der Ree, T., (Westfriesgasthuis, Md, Hoorn, Roodbol, J., Sachs, G. M., MD (University of Rhode Island, Providence, USA), Samijn, J. P. A., PhD (Maasstad Hospital, Santoro, L., PhD (University Federico II, Napels, Italy), Stein, B., Joseph’s Regional Medical Center, MD (St., Paterson, USA), Vermeij, F. H., MD (Franciscus Gasthuis, Visser, L. H., PhD (Elisabeth-TweeSteden Hospital, Tilburg and Waalwijk, Willison, H. J., PhD (University of Glasgow, Wirtz, P., Phd, (HagaZiekenhuis, Zivkovich, S. A., PhD (University of Pittsburgh Medical Center, and Pittsburgh, USA).
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treatment ,disability evaluation ,drug administration schedule ,adult ,guillain-barré syndrome ,poor prognosis ,second ivig course ,aged ,female ,guillain-barre syndrome ,humans ,immunoglobulin g ,immunoglobulins ,intravenous ,immunologic factors ,male ,middle aged ,prognosis ,time factors ,treatment outcome - Published
- 2020
7. Restoration of Replication Phenotype of Lamivudine-Resistant Hepatitis B Virus Mutants by Compensatory Changes in the “Fingers” Subdomain of the Viral Polymerase Selected as a Consequence of Mutations in the Overlapping S Gene
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Torresi, Joseph, Earnest-Silveira, Linda, Civitico, Gilda, Walters, Tomos E., Lewin, Sharon R., Fyfe, Janet, Locarnini, Stephen A., Manns, Michael, Trautwein, Christian, and Bock, Thomas C.
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- 2002
- Full Text
- View/download PDF
8. Ultra-Early, Minimally inVAsive intraCerebral Haemorrhage evacUATion Versus Standard trEatment (EVACUATE)
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Bruce Campbell, Professorial Fellow, Department of Medicine, Royal Melbourne Hospital, Faculty of Medicine, Dentistry and Health Sciences
- Published
- 2024
9. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
- Author
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[ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
- Abstract
To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
10. Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis
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Georgina Arrambide, Ingrid van der Mei, Raed Alroughani, Lars Forsberg, Rodden M. Middleton, Guilherme Sciascia do Olival, Nikola Lazovski, Rumen Ivanov, Alexander Stahmann, Tomas Kalincik, Helmut Butzkueven, Richard S. Nicholas, J. Hillert, Alice Estavo Dias, Edward De Brouwer, Amber Salter, Serkan Ozakbas, Nupur Nag, Doralina Guimarães Brum, Alexander Fidao, Anna Zabalza, Yves Moreau, Ricardo Alonso, Anneke Van Der Walt, Nick Rijke, Lotte Geys, Anibal Chertcoff, Arnfin Bergmann, Robert N. McBurney, Clare Walton, Anna Glaser, Tina Parciak, Gilles Edan, Clément Gautrais, Ashkan Pirmani, Maria Fernanda Mendes, Juan Ignacio Rojas, Melinda Magyari, Liesbet M. Peeters, Robert J. Fox, Hollie Schmidt, Amin Ardeshirdavanai, Steve Simpson-Yap, Stefan Braune, Giancarlo Comi, Johana Bauer, Tim Spelman, Zabalza, Ana/0000-0003-3860-5251, Simpson, Jr., Steve/0000-0001-6521-3056, Kalincik, Tomas/0000-0003-3778-1376, Simpson-Yap, Steve, DE BROUWER, Edward, Kalincik, Tomas, Rijke, Nick, Hillert, Jan A., Walton, Clare, Edan, Gilles, Moreau, Yves, Spelman, Tim, GEYS, Lotte, PARCIAK, Tina, Gautrais, Clement, Lazovski, Nikola, PIRMANI, Ashkan, Ardeshirdavanai, Amin, Forsberg, Lars, Glaser, Anna, McBurney, Robert, Schmidt, Hollie, Bergmann, Arnfin B., Braune, Stefan, Stahmann, Alexander, Middleton, Rodden, Salter, Amber, Fox, Robert J., van der Walt, Anneke, Butzkueven, Helmut, Alroughani, Raed, Ozakbas, Serkan, Rojas, Juan, I, van der Mei, Ingrid, Nag, Nupur, Ivanov, Rumen, do Olival, Guilherme Sciascia, Dias, Alice Estavo, Magyari, Melinda, Brum, Doralina, Mendes, Maria Fernanda, Alonso, Ricardo N., Nicholas, Richard S., Bauer, Johana, Chertcoff, Anibal Sebastian, Zabalza, Anna, Arrambide, Georgina, Fidao, Alexander, Comi, Giancarlo, PEETERS, Liesbet, Institut Català de la Salut, [Simpson-Yap S] Department of Medicine, and Neuroepidemiology Unit, Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia [De Brouwer E] University of Tasmania, Hobart, Australia. ESAT-STADIUS, KU Leuven, Belgium. [Kalincik T] Department of Neurology, Melbourne MS Centre, Royal Melbourne Hospital, Parkville, Australia. [Rijke N, Walton C] MS International Federation, London, UK. [Hillert JA] Department of Clinical Neuroscience, Swedish MS Registry, Stockholm, Sweden. [Zabalza A, Arrambide G] Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, and Neuroepidemiology Unit, Melbourne School of Population and Global Health, University of Tasmania, KU Leuven, Royal Melbourne Hospital, MS International Federation, Swedish MS Registry, CHU Pontchaillou, Karolinska Institutet, Hasselt University, University Medical Center, QMENTA, Molecular Unit, Accelerated Cure Project for MS, NeuroTransData, MS Forschungs- und Projektentwicklungs-gGmbH, Swansea University, COViMS, Washington University in St. Louis, Cleveland Clinic, Monash University, Kuwait City, Dokuz Eylul University, Hospital Universitario de CEMIC, RELACOEM, Bulgarian SmartMS COVID-19 Dataset, ABEM-Brazilian MS Patients Association, University Hospital Rigshospitalet, Universidade Estadual Paulista (UNESP), REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders, Irmandade da Santa Casa de Misericórdia de São Paulo, Ramos Mejia Hospital-EMA, Imperial College, Mental Health Area, EMA, Cemcat, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, and Ospedale San Raffaele
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Male ,Dimethyl Fumarate ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores] ,chemistry.chemical_compound ,0302 clinical medicine ,Natalizumab ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Medicine ,10. No inequality ,COVID-19 (Malaltia) - Complicacions ,B-Lymphocytes ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES] ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,Middle Aged ,3. Good health ,Hospitalization ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] ,Cohort ,Female ,Rituximab ,Life Sciences & Biomedicine ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Clinical Neurology ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Antibodies, Monoclonal, Humanized ,Young Adult ,03 medical and health sciences ,Internal medicine ,Humans ,Risk factor ,Aged ,030203 arthritis & rheumatology ,Science & Technology ,Expanded Disability Status Scale ,SARS-CoV-2 ,business.industry ,COVID-19 ,Odds ratio ,Respiration, Artificial ,Cross-Sectional Studies ,Siponimod ,chemistry ,Ocrelizumab ,Neurosciences & Neurology ,Neurology (clinical) ,business ,Esclerosi múltiple - Tractament ,030217 neurology & neurosurgery ,Other subheadings::Other subheadings::/complications [Other subheadings] - Abstract
Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina
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- 2021
11. An exploration of the political, social, economic and cultural factors affecting how different global regions initially reacted to the COVID-19 pandemic
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Julian W. Tang, Miguela A. Caniza, Mike Dinn, Dominic E. Dwyer, Jean-Michel Heraud, Lance C. Jennings, Jen Kok, Kin On Kwok, Yuguo Li, Tze Ping Loh, Linsey C. Marr, Eva Megumi Nara, Nelun Perera, Reiko Saito, Carlos Santillan-Salas, Sheena Sullivan, Matt Warner, Aripuanã Watanabe, Sabeen Khurshid Zaidi, University of Leicester, St Jude Children's Research Hospital, The University of Sydney, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), The Chinese University of Hong Kong [Hong Kong], The University of Hong Kong (HKU), National University Hospital [Singapore] (NUH), Virginia Tech [Blacksburg], Universidad Nacional de Asunción [Paraguay] (UNA), University Hospitals Leicester, Niigata University, Instituto Nacional de Salud del Niño San Borja, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, University Hospitals Plymouth NHS Trust [Plymouth, UK] (UHP), Universidade Federal de Juiz de Fora (UFJF), and Karachi Institute of Medical Sciences [Karachi, Pakistan] (KIMS)
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[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,SARS-CoV-2 ,government ,Biomedical Engineering ,Biophysics ,COVID-19 ,Bioengineering ,Biochemistry ,lockdown ,Coronavirus ,Biomaterials ,pandemic response ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Health ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,guidance ,Biotechnology - Abstract
International audience; Responses to the early (February–July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the various pandemic restrictions, like masking, social distancing and self-isolation or self-quarantine. The degree of compliance with these measures depended on how much individuals valued their needs and liberties over those of their society. Thus, several themes may be relevant when comparing pandemic responses across different regions. East and Southeast Asian populations tended to be more collectivist and self-sacrificing, responding quickly to early signs of the pandemic and readily complied with most restrictions to control its spread. Australasian, Eastern European, Scandinavian, some Middle Eastern, African and South American countries also responded promptly by imposing restrictions of varying severity, due to concerns for their wider society, including for some, the fragility of their healthcare systems. Western European and North American countries, with well-resourced healthcare systems, initially reacted more slowly, partly in an effort to maintain their economies but also todelay imposing pandemic restrictions that limited the personal freedoms of their citizens.
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- 2022
12. Partial oral antibiotic treatment for bacterial brain abscess:an open-label randomized non-inferiority trial (ORAL)
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Steven Y. C. Tong, Henrik Nielsen, Jacob Bodilsen, Diederik van de Beek, Pontus Naucler, Pierre Tattevin, Matthijs C. Brouwer, Aalborg University [Denmark] (AAU), University of Amsterdam [Amsterdam] (UvA), ESCMID [Basel], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Karolinska University Hospital [Stockholm], Clinical-Microbiomics, The study has been funded by the Novo Nordisk Foundation (Grant 0057510). The funder will play no part in study design, collection, management, analysis, and interpretation of data, writing of the report, and the decision to submit the report for publication., Jonchère, Laurent, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Adult ,Oral ,Medicine (General) ,medicine.medical_specialty ,Randomization ,[SDV]Life Sciences [q-bio] ,Medicine (miscellaneous) ,law.invention ,Non-inferiority ,03 medical and health sciences ,Study Protocol ,R5-920 ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,Antibiotics ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Adverse effect ,Brain abscess ,Brain Abscess/diagnosis ,business.industry ,Glasgow Outcome Scale ,Standard treatment ,COVID-19 ,medicine.disease ,Anti-Bacterial Agents/adverse effects ,Anti-Bacterial Agents ,3. Good health ,[SDV] Life Sciences [q-bio] ,Treatment ,Treatment Outcome ,Quality of Life ,Cerebral abscess ,business ,Intravenous ,030217 neurology & neurosurgery - Abstract
Background The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective. Methods This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6–8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients. Discussion The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits. Trial registration ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019
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- 2021
13. Pharmaquiz.
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Royal Melbourne Hospital Pharmacy Department
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- 1982
14. Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects
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Lisa Devereux, Douglas F. Easton, Simone McInerny, Melissa C. Southey, R. K. Schmutzler, Orland Diez, Muriel A. Adank, Tu Nguyen-Dumont, Alfons Meindl, Alejandro Moles-Fernández, Marjanka K. Schmidt, Rodney J. Scott, Martine Dumont, Paul A. James, Christoph Engel, Fabienne Lesueur, Penny Soucy, Yu Kuan Huang, N Li, Elad Ziv, Elodie Girard, Eric Hahnen, Magnus Zethoven, Jamie Allen, Kylie L. Gorringe, Susan L. Neuhausen, Irene L. Andrulis, Dane Cheasley, Jacques Simard, John L. Hopper, Ian G. Campbell, Niko Thio, Sara Gutiérrez-Enríquez, Institut Català de la Salut, [Li N] Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic, Australia. Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Vic, Australia. [Zethoven M] Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. Bioinformatics Core Facility, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. [McInerny S] Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Vic, Australia. [Devereux L] Lifepool, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. [Huang YK] Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Vic, Australia. [Thio N] Bioinformatics Core Facility, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia. [Gutiérrez-Enríquez S, Moles-Fernández A] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Diez O] Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Hospital Universitari Vall d’Hebron, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Li, Na [0000-0003-1578-9561], Devereux, Lisa [0000-0003-2435-5888], Huang, Yu-Kuan [0000-0003-2262-7069], Cheasley, Dane [0000-0002-1170-4690], Gutiérrez-Enríquez, Sara [0000-0002-1711-6101], Simard, Jacques [0000-0001-6906-3390], Schmidt, Marjanka K [0000-0002-2228-429X], Andrulis, Irene L [0000-0002-4226-6435], Engel, Christoph [0000-0002-7247-282X], Lesueur, Fabienne [0000-0001-7404-4549], Easton, Douglas F [0000-0003-2444-3247], Scott, Rodney J [0000-0001-7724-3404], Gorringe, Kylie L [0000-0001-5681-2022], James, Paul A [0000-0002-4361-4657], Campbell, Ian G [0000-0002-7773-4155], Apollo - University of Cambridge Repository, Allen, Jamie [0000-0002-8677-2225], Schmidt, Marjanka K. [0000-0002-2228-429X], Andrulis, Irene L. [0000-0002-4226-6435], Easton, Douglas F. [0000-0003-2444-3247], Scott, Rodney J. [0000-0001-7724-3404], Gorringe, Kylie L. [0000-0001-5681-2022], James, Paul A. [0000-0002-4361-4657], and Campbell, Ian G. [0000-0002-7773-4155]
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0301 basic medicine ,Oncology ,Mama - Càncer - Prognosi ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES] ,Diàtesi ,32 Biomedical and Clinical Sciences ,medicine.disease_cause ,631/208/737 ,Germline ,0302 clinical medicine ,Other subheadings::/diagnosis [Other subheadings] ,Missense mutation ,2.1 Biological and endogenous factors ,Pharmacology (medical) ,631/208/68 ,RC254-282 ,Cancer ,2 Aetiology ,Mutation ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,medicine.diagnostic_test ,article ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,4203 Health Services and Systems ,3. Good health ,030220 oncology & carcinogenesis ,Malalties congènites ,Haploinsufficiency ,medicine.medical_specialty ,DNA repair ,Otros calificadores::/diagnóstico [Otros calificadores] ,631/67/69 ,03 medical and health sciences ,Breast cancer ,Clinical Research ,Internal medicine ,Breast Cancer ,medicine ,Genetics ,Radiology, Nuclear Medicine and imaging ,Genetic Testing ,Genetic testing ,fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS] ,business.industry ,Prevention ,Human Genome ,42 Health Sciences ,631/67/1347 ,medicine.disease ,3211 Oncology and Carcinogenesis ,631/208/199 ,030104 developmental biology ,business - Abstract
Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82–1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09–1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.
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- 2021
15. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults
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Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung-Soo Yoon, David Kavanagh, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Josep M. Campistol, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Eric Rondeau, Hermann Haller, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin K.S. Wong, Barbour T., Scully M., Ariceta G., Cataland S., Garlo K., Heyne N., Luque Y., Menne J., Miyakawa Y., Yoon S.-S., Kavanagh D., Babu S., Broeders N., Lietar N., Brown F., Campbell P., Campistol J.M., Chowdhury P., Kasimatis T., Cirami L., Caroti L., Antognoli G., Delmas Y., Dobronravov V., Gaeckler A., Garrouste C., Greenwood G., Griffin S., Huang C.-C., Chen I.-R., Huang S., Kim J.S., La Manna G., Le Quintrec M., Jeantet G., Fumie I., Rondeau E., Haller H., Morelle J., Goffin E., Muhlfeld A., Nagaraj S., Arepally G., Oh D., Okumi M., Terente M.P., Provot F., Schonermarck U., Fischereder M., Terrada N.R., Seitz-Polski B., Favre G., Boyer-Suavet S., Vinogradova M., Kirsanova T., Wong E.K.S., Institut Català de la Salut, [Barbour T] Kidney Care, The Royal Melbourne Hospital, Melbourne, Australia. [Scully M] Department of Haematology, University College London Hospitals, London, UK. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Cataland S] Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio, USA. [Garlo K] Clinical Development, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USA. [Heyne N] Section of Nephrology and Hypertension, Tübingen University Hospital, Tübingen, Germany, Vall d'Hebron Barcelona Hospital Campus, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, The Royal Melbourne Hospital, University College London Hospitals (UCLH), Vall d'Hebron University Hospital [Barcelona], Ohio State University [Columbus] (OSU), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Seoul National University Hospital, and Newcastle University [Newcastle]
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medicine.medical_specialty ,Thrombotic microangiopathy ,[SDV]Life Sciences [q-bio] ,Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Hemolytic-Uremic Syndrome::Hemic and Lymphatic Diseases::Hematologic Diseases::Atypical Hemolytic Uremic Syndrome [DISEASES] ,030232 urology & nephrology ,Renal function ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,030204 cardiovascular system & hematology ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,03 medical and health sciences ,0302 clinical medicine ,afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras [ENFERMEDADES] ,Clinical Research ,Internal medicine ,Atypical hemolytic uremic syndrome ,Medicine ,complement ,Adverse effect ,Complement component 5 ,business.industry ,Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases [DISEASES] ,atypical hemolytic uremic syndrome ,Acute kidney injury ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,medicine.disease ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,ravulizumab ,Diseases of the genitourinary system. Urology ,3. Good health ,enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::síndrome hemolítico-urémico::enfermedades hematológicas y linfáticas::enfermedades hematológicas::síndrome hemolítico urémico atípico [ENFERMEDADES] ,kidney failure ,thrombotic microangiopathy ,Clinical trial ,Nephrology ,Avaluació de resultats (Assistència sanitària) ,hemolytic uremic syndrome ,RC870-923 ,Síndrome hemolíticourèmica - Tractament ,Malalties rares ,business ,Kidney disease - Abstract
Hemolytic uremic syndrome; Kidney failure; Ravulizumab Síndrome hemolítico urémico; Insuficiencia renal; Ravulizumab Síndrome hemolític urèmic; Insuficiència renal; Ravulizumab Introduction Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. Methods The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6–118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. Results A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. Conclusion This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment.
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- 2021
16. Population genomics and antimicrobial resistance in Corynebacterium diphtheriae
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Sarah L. Baines, Julie Toubiana, Annick Carmi-Leroy, Marina Barros-Pinkelnig, Carla Rodrigues, Anne Marie Wehenkel, Xavier Didelot, Sylvain Brisse, Leonardo G. Panunzi, Edgar Badell, Melanie Hennart, Quentin Gaday, Melody Dazas, Brisse, Sylvain, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Klebsiella pneumoniae: from ecology to source attribution and transmission control - MedVetKlebs (a component of European Joint Programme One Health) - - H2020-SFS-2017-12018-01-01 - 2019-12-31 - 773830 - VALID, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Collège Doctoral, Sorbonne Université (SU), Institut Français de Bioinformatique (IFB-CORE), Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), University of Warwick [Coventry], Département de Pédiatrie et maladies infectieuses [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), Université Paris Cité (UPCité), MH was supported financially by a PhD grant from the European Joint Programme One Health, which has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 773830. LGP was supported financially by a grant from the Institut Français de Bioinformatique, the national infrastructure for services in bioinformatics created in the frame of the French Government’s Investissement d’Avenir program. QG was funded by MTCI PhD school (ED 563). CR was supported by a Pasteur-Roux fellowship from Institut Pasteur. SLB received support from a Victorian Fellowship, provided by VESKI and funded by the State Government of Victoria, Australia. The National Reference Center for Corynebacteria of the Diphtheriae complex receives support from Institut Pasteur and Public Health France (Santé Publique France, Saint Maurice, France). This work was supported financially by the French government’s Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). AW and QG receive support from Institut Pasteur and the CNRS (France)., We thank Vincent Enouf and the P2M core facility of Institut Pasteur for genomic sequencing. We are indebted to Collection de l’Institut Pasteur for providing reference strains of ribotypes, which were deposited following their described by Grimont and colleagues in 2004. We thank Valerie Bouchez for help with the Oxford Nanopore Technologies sequencing., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Institut Pasteur [Paris], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The Royal Melbourne Hospital-University of Melbourne, Collège doctoral [Sorbonne universités], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)
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0301 basic medicine ,Antibiotic resistance ,Biovar ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Diphtheria Toxin ,Prospective Studies ,Genetics (clinical) ,Phylogeny ,Genetics ,education.field_of_study ,biology ,Diphtheria ,Genomics ,Antimicrobial ,C. diphtheriae ,3. Good health ,Anti-Bacterial Agents ,Horizontal gene transfer ,Molecular Medicine ,Macrolides ,DNA, Bacterial ,Genome-wide association study ,lcsh:QH426-470 ,030106 microbiology ,Population ,Microbial Sensitivity Tests ,[SDV.BID]Life Sciences [q-bio]/Biodiversity ,Mobile genetic element ,03 medical and health sciences ,Drug Resistance, Bacterial ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,education ,Molecular Biology ,Corynebacterium diphtheriae ,Diphtheria toxin ,Research ,lcsh:R ,biology.organism_classification ,medicine.disease ,QR ,lcsh:Genetics ,030104 developmental biology ,Genes, Bacterial ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Metagenomics ,Multilocus Sequence Typing ,[SDV.BID] Life Sciences [q-bio]/Biodiversity - Abstract
BackgroundCorynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen.MethodsHere, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features inC. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories.ResultsPhylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Genepbp2mis widespread in otherCorynebacteriumspecies, and its expression inC. glutamicumdemonstrated its effect against several beta-lactams. A novel 73-kbC. diphtheriaemultiresistance plasmid was discovered.ConclusionsThis work uncovers the dynamics of antimicrobial resistance inC. diphtheriaein the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.
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- 2020
17. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer
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Hovens, Christopher [Royal Melbourne Hospital and Univ. of Melbourne, Victoria (Australia); Epworth Hospital, Victoria (Australia)]
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- 2015
- Full Text
- View/download PDF
18. 'Light' Versus 'Deep' Bispectral Index (BIS) Guided Sedation for Colonoscopy
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Associate Professor Kate Leslie, Head of Reaseach and Staff anaesthetist, The Royal Melbourne Hospital
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- 2015
19. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells
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John Zaunders, Yin Xu, Chansavath Phetsouphanh, Kazuo Suzuki, Anu Aggrawal, Stephanie Graff-Dubois, Michael Roche, Michelle Bailey, Sheilajen Alcantara, Kieran Cashin, Rahuram Sivasubramaniam, Kersten K. Koelsch, Brigitte Autran, Richard Harvey, Paul R. Gorry, Arnaud Moris, David A. Cooper, Stuart Turville, Stephen J. Kent, Anthony D. Kelleher, The Kirby Institute, University of New South Wales [Sydney] (UNSW), St. Vincent's Centre for Applied Medical Research, St Vincent's Hospital Sydney, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), The Peter Doherty Institute for Infection and Immunity [Melbourne], The Royal Melbourne Hospital-University of Melbourne, Burnet Institute [Melbourne, Victoria], Service d'Immunologie [CHU Pitié-Salpétrière], 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), Royal Melbourne Institute of Technology University (RMIT University), Monash University [Clayton], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Melbourne-The Royal Melbourne Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL UPMC, Gestionnaire
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,T cell ,viruses ,Population ,Immunology ,Biology ,03 medical and health sciences ,Immune system ,medicine ,Immunology and Allergy ,education ,Tropism ,Original Research ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,education.field_of_study ,T-cell receptor ,Germinal center ,virus diseases ,Provirus ,BCL6 ,Virology ,CD4 ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,germinal center ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,HIV-1 ,T follicular helper cells ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,lcsh:RC581-607 ,CCR5 - Abstract
Background T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells. Methodology Tfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay. Results Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int)+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils. Conclusion The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important for establishing effective immune responses during primary infections, Tfh are likely to be an early target of HIV-1 following transmission, creating an important component of the reservoir that has the potential to expand over time.
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- 2017
20. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study
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Sandra Nolte, Laura L Laslett, Anthony D. Woolf, Emma Smith, Theo Vos, Damian G Hoy, Ilana N. Ackerman, Marita Cross, Richard H. Osborne, Marlene Fransen, Flavia M. Cicuttini, Lisa Bridgett, Rachelle Buchbinder, Graeme Jones, Lyn March, Sean R.M. Williams, Francis Guillemin, Christopher Hill, Institute of Bone & Joint Research, Royal North Shore Hospital (RNSH)-The University of Sydney, School of Population Health, University of Queensland, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Institute of Public Health [Berlin, Germany], School of Health and Social Development [Deakin University], Deakin University [Burwood], The Royal Melbourne Hospital, Melbourne EpiCentre, Faculty of Health Sciences [University of Sydney], The University of Sydney, School of Medicine [Western Sydney University], Western Sydney University (UWS), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), The Queen Elizabeth Hospital, Adelaide, The Health Observatory [University of Adelaide], University of Adelaide, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania (UTAS), Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia, Monash University [Clayton], Institute for Health Metrics and Evaluation [University of Washington], University of Washington [Seattle], Cabrini Institute, Monash University [Melbourne], Royal Cornwall Hospital, Royal North Shore Hospital ( RNSH ) -The University of Sydney [Sydney], Charite-Universitatsmedizin Berlin [Berlin], Hôpital universitaire de la Charité de Berlin, Melbourne Medical School-The Royal Melbourne Hospital, The University of Sydney [Sydney], Western Sydney University ( UWS ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Western Sydney University, and University of Tasmania [Hobart, Australia] (UTAS)
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Male ,MESH : Prevalence ,Epidemiology ,MESH : Age Distribution ,MESH : Aged ,MESH: Global Health ,Osteoarthritis ,MESH : Child, Preschool ,Global Health ,MESH: Regression Analysis ,Severity of Illness Index ,Osteoarthritis, Hip ,MESH: Aged, 80 and over ,MESH : Child ,Cost of Illness ,MESH : Regression Analysis ,MESH: Child ,MESH: Osteoarthritis, Knee ,Prevalence ,Immunology and Allergy ,MESH : Cost of Illness ,MESH : Female ,MESH: Incidence ,Young adult ,Child ,MESH : Sex Distribution ,MESH: Aged ,Aged, 80 and over ,education.field_of_study ,MESH: Middle Aged ,Incidence ,Incidence (epidemiology) ,MESH: Sex Distribution ,MESH : Infant ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH : Adult ,MESH: Cost of Illness ,Middle Aged ,Osteoarthritis, Knee ,MESH: Infant ,MESH : Incidence ,3. Good health ,MESH: Quality-Adjusted Life Years ,MESH: Young Adult ,Child, Preschool ,Regression Analysis ,MESH : Severity of Illness Index ,Female ,Quality-Adjusted Life Years ,MESH : Osteoarthritis, Hip ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Adolescent ,MESH : Male ,Immunology ,Population ,MESH : Young Adult ,General Biochemistry, Genetics and Molecular Biology ,Knee Osteoarthritis ,Young Adult ,Age Distribution ,Rheumatology ,MESH : Adolescent ,MESH: Severity of Illness Index ,Severity of illness ,medicine ,Humans ,MESH : Middle Aged ,MESH : Osteoarthritis, Knee ,Sex Distribution ,MESH : Aged, 80 and over ,education ,MESH: Age Distribution ,MESH: Prevalence ,Aged ,MESH: Adolescent ,MESH: Humans ,business.industry ,MESH : Humans ,MESH: Child, Preschool ,Infant ,MESH: Adult ,MESH : Quality-Adjusted Life Years ,medicine.disease ,Obesity ,MESH: Male ,Quality-adjusted life year ,Physical therapy ,MESH : Global Health ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: Osteoarthritis, Hip ,business ,MESH: Female - Abstract
International audience; OBJECTIVE:To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions.METHODS:Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs).RESULTS:Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs).CONCLUSIONS:Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.
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- 2014
21. Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria
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Eva C. Boritsch, Victor H. Navas, Torsten Seemann, Roland Brosch, Philip Supply, Christiane Bouchier, Timothy P. Stinear, Laurence Ma, Nadine Honoré, Varun Khanna, Alexandre Pawlik, Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris] (IP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique (Plate-Forme) - Genomics Platform, Victorian Life Sciences Computation Initiative, University of Melbourne, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, This study was in part supported by the European Community’s Grants 260872 and 643381, European Union - European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Grant 115337, Agence National de Recherche Grant ANR-14-JAMR-001-02, and Fondation pour la Recherche Médicale FRM Grant DEQ20130326471. R.B. is a member of the LabEx consortium ANR-10-LABX-62-IBEID at the Institut Pasteur. E.C.B. was supported by a stipend from the Pasteur–Paris University International PhD program and the Institut Carnot Pasteur Maladies Infectieuses., We thank William R. Jacobs for providing M. smegmatis mc2874 and M. tuberculosis ΔRD1 strains, Denis A. Mitchison for providing M. tuberculosis strain 79112, and Dick van Soolingen for M. tuberculosis strain Tb36. We thank Louis Jones for setup of the CanettiiList server. Whole-genome sequencing was performed at the Institut Pasteur Genomics Platform, member of the 'France Génomique' consortium (ANR10-INBS-09-08). We thank the students of the Institut Pasteur genome analysis course for contributing one M. smegmatis clone for further analysis., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], 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), and The Royal Melbourne Hospital-University of Melbourne
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0301 basic medicine ,DNA transfer ,DNA, Bacterial ,MESH: Genome, Bacterial / genetics ,MESH: DNA, Bacterial / genetics ,Gene Transfer, Horizontal ,030106 microbiology ,Virulence ,Biology ,Genome ,Mycobacterium ,Mycobacterium tuberculosis ,Evolution, Molecular ,03 medical and health sciences ,Species Specificity ,MESH: Mycobacterium / classification ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,evolution ,MESH: Species Specificity ,Humans ,Tuberculosis ,MESH: Evolution, Molecular ,MESH: Tuberculosis / microbiology ,Whole genome sequencing ,Genetics ,MESH: Gene Transfer, Horizontal ,Multidisciplinary ,MESH: Humans ,MESH: Mycobacterium tuberculosis / physiology ,Whole Genome Sequencing ,Mycobacterium canettii ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,MESH: Mycobacterium / physiology ,MESH: Mycobacterium tuberculosis / classification ,MESH: Whole Genome Sequencing / methods ,Biological Sciences ,biology.organism_classification ,recombination ,3. Good health ,MESH: Mycobacterium / genetics ,030104 developmental biology ,Mycobacterium tuberculosis complex ,MESH: Mycobacterium tuberculosis / genetics ,Horizontal gene transfer ,Human genome ,Genome, Bacterial - Abstract
International audience; Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of dominant lineages remains a matter of debate. Here, by using fluorescence-assisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade. We found that the obtained recombinants had received multiple donor-derived DNA fragments in the size range of 100 bp to 118 kbp, fragments large enough to contain whole operons. Although the transfer frequency between M. canettii strains was low and no transfer could be observed among classical Mycobacterium tuberculosis complex (MTBC) strains, our study provides the proof of concept for genetic exchange in tubercle bacilli. This outstanding, now experimentally validated phenomenon presumably played a key role in the early evolution of the MTBC toward pathogenicity. Moreover, our findings also provide important information for the risk evaluation of potential transfer of drug resistance and fitness mutations among clinically relevant mycobacterial strains.
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- 2016
22. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012
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Byung Ihn Choi, Jean Michel Correas, Hong Ding, David O. Cosgrove, Edward Leen, Nitin Chaubal, Min-hua Chen, Robert F. Mattrey, Richard G. Barr, Nathalie Lassau, Barry B. Goldberg, Luigi Solbiati, Hans Peter Weskott, Christian Pállson Nolsøe, J. Brian Fowlkes, Maria Cristina Chammas, Fuminori Moriyasu, Fabio Piscaglia, Hui-Xiong Xu, Robert N Gibson, Michel Claudon, Flemming Forsberg, Dirk-André Clevert, Stephanie R. Wilson, Masatoshi Kudo, Christoph F. Dietrich, Département de Radiologie adultes [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Caritas-Krankenhaus Bad Mergentheim, Seoul National University Hospital, Hammersmith Hospital & Imperial College, Department of Gastroenterology and Hepatology, Kinki/Kindai University School of Medicine, Kindai University-Kindai University, Herlev and Gentofte Hospital, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of Calgary, Northeastern Ohio Medical University (NEOMED), Universidade de Sao Paolo, Philosophy Department, Thane Ultrasound Centre, Jaslok Hospital & Research Centre, Beijing University Cancer Hospital, University-Hospital Munich-Großhadern [München], Service de radiologie [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), Zhongshan Hospital, Fudan University [Shanghai], Thomas Jefferson University, University of Michigan [Ann Arbor], University of Michigan System, Department of Radiology, Royal Melbourne Hospital, Melbourne University, VIC, Parkville, Australia, department of Radiology, Royal Melbourne Hospital-Royal Melbourne Hospital, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), University of California [San Diego] (UC San Diego), University of California, Tokyo Medical University, General Hospital of Busto Arsizio, Klinikum Region Hannover, and Tongji University
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Liver surgery ,medicine.medical_specialty ,Acoustics and Ultrasonics ,Hepatocellular carcinoma ,Diagnostico diferencial ,Biophysics ,MEDLINE ,Metastases ,Microbubble ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Diagnosis ,Focal nodular hyperplasia ,medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Radiological and Ultrasound Technology ,business.industry ,Ultrasound ,3. Good health ,Surgery ,030220 oncology & carcinogenesis ,Good clinical practice ,030211 gastroenterology & hepatology ,Radiology ,Ultrasonography ,Hemangioma ,business ,Liver pathology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Contrast-enhanced ultrasound - Abstract
International audience; Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.
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- 2012
23. State of Acute Endovascular Therapy
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Khatri, Pooja, Hacke, Werner, Fiehler, Jens, Saver, Jeffrey, Diener, Hans-Christoph, Bendszus, Martin, Bracard, Serge, Broderick, Joseph, Campbell, Bruce, Ciccone, Alfonso, Dávalos, Antoni, Davis, Stephen, Demchuk, Andrew, Dippel, Diederik, Donnan, Geoffrey, Fiorella, David, Goyal, Mayank, Hill, Michael, Jauch, Edward, Jovin, Tudor, Kidwell, Chelsea, Majoie, Charles, Martins, Sheila Cristina Ouriques, Mitchell, Peter, Mocco, J., Muir, Keith, Nogueira, Raul, Schonewille, Wouter, Siddiqui, Adnan, Thomalla, Götz, Tomsick, Thomas, Turk, Aquilla, White, Philip, Zaidat, Osama, Liebeskind, David, Fulton, Rachel, Lees, Kennedy, Department of Neurology and Rehabilitation Medicine [Cincinnati], University of Cincinnati (UC), Department of Neurology [University of Heidelberg], Universität Heidelberg [Heidelberg]-Heidelberg University Hospital [Heidelberg], Departments of Diagnostic and Interventional Neuroradiology [MC Hamburg-Eppendorf], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Comprehensive Stroke Center, University of California [Los Angeles] (UCLA), University of California-University of California, Department of Neurology [UCLA], University of California-University of California-David Geffen School of Medicine [Los Angeles], Department of Neurology [Duisburg-Essen], Universität Duisburg-Essen [Essen], Department of Neuroradiology [Universität Heidelberg], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Department of Medicine and Neurology [University of Melbourne], University of Melbourne, Carlo Poma Hospital Mantova (ASST Mantova ), Department of Neurosciences [Universitat Autònoma de Barcelona], Universitat Autònoma de Barcelona (UAB), Department of Clinical Neuroscience [University of Calgary], University of Calgary, Department of Neurology [University of Calgary], Erasmus University Medical Center [Rotterdam] (Erasmus MC), The Florey Institute of Neuroscience and Mental Health, Department of Neurosurgery [Stony Brook University], Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Department of Diagnostic and Interventional Neuroradiology [University of Calgary], Departments of Clinical Neurosciences and Oncology [University of Calgary], Department of Emergency Medicine [Medical University of South Carolina], Medical University of South Carolina [Charleston] (MUSC), Department of Neurology [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Neurology [University of Arizona], University of Arizona, Department of Medical Imaging [University of Arizona], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Hospital de Clínicas de Porto Alegre (HCPA), Department of Radiology, Royal Melbourne Hospital, Melbourne University, VIC, Parkville, Australia, department of Radiology, Royal Melbourne Hospital-Royal Melbourne Hospital, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Emory University [Atlanta, GA], Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Department of Neurology [MC Hamburg-Eppendorf], Department of Radiology [Cincinnati], Departments of Radiology and Neurosurgery [Medical University of South Carolina], Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Medical College of Wisconsin, and Institute of Cardiovascular and Medical Sciences [Glasgow]
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thrombectomy ,clinical trial ,ComputingMilieux_MISCELLANEOUS ,thrombolysis therapy ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2015
24. Promiscuous evolution of Group A Streptococcal M and M-like proteins
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Hannah R. Frost, Julien Guglielmini, Sebastian Duchêne, Jake A. Lacey, Martina Sanderson-Smith, Andrew C. Steer, Mark J. Walker, Anne Botteaux, Mark R. Davies, Pierre R. Smeesters, Université libre de Bruxelles (ULB), Murdoch Children's Research Institute (MCRI), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, University of Wollongong [Australia], University of Melbourne, University of Queensland [Brisbane], and The work is supported by the Belgian Fonds National de la Recherche Scientifique (FNRS) research grants (PDR T.0255.16 and CDR J.0019.17).
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[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Virulence ,Streptococcus pyogenes ,Typing ,MGA regular ,Vaccine ,Surface protein ,Microbiology - Abstract
Group A Streptococcus (GAS) M and M-like proteins are essential virulence factors and represent the primary epidemiological marker of this pathogen. Protein sequences encoding 1054 M, Mrp and Enn proteins, from 1668 GAS genomes, were analysed by SplitsTree4, partitioning around medoids and co-occurrence. The splits network and groups-based analysis of all M and M-like proteins revealed four large protein groupings, with multiple evolutionary histories as represented by multiple edges for most splits, leading to ‘M-family-groups’ (FG) of protein sequences: FG I, Mrp; FG II, M protein and Protein H; FG III, Enn; and FG IV, M protein. M and Enn proteins formed two groups with nine sub-groups and Mrp proteins formed four groups with ten sub-groups. Discrete co-occurrence of M and M-like proteins were identified suggesting that while dynamic, evolution may be constrained by a combination of functional and virulence attributes. At a granular level, four distinct family-groups of M, Enn and Mrp proteins are observable, with Mrp representing the most genetically distinct of the family-group of proteins. While M and Enn protein families generally group into three distinct family-groups, horizontal and vertical gene flow between distinct GAS strains is ongoing.
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- 2023
25. COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey
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Hoff, Leonardo Santos, Ravichandran, Naveen, Shinjo, Samuel Katsuyuki, Day, Jessica, Sen, Parikshit, Junior, Jucier Gonçalves, Lilleker, James B., Joshi, Mrudula, Agarwal, Vishwesh, Kardes, Sinan, Kim, Minchul, Milchert, Marcin, Makol, Ashima, Gheita, Tamer, Salim, Babur, Velikova, Tsvetelina, Gracia-Ramos, Abraham Edgar, Parodis, Ioannis, Selva O'Callaghan, Albert, Nikiphorou, Elena, Tan, Ai Lyn, Chatterjee, Tulika, Cavagna, Lorenzo, Saavedra, Miguel A., Ziade, Nelly, Knitza, Johannes, Kuwana, Masataka, Nune, Arvind, Distler, Oliver, Cansu, Döndü Üsküdar, Traboco, Lisa, Wibowo, Suryo Angorro Kusumo, Tehozol, Erick Adrian Zamora, Serrano, Jorge Rojas, La Torre, Ignacio García-De, Wincup, Chris, Pauling, John D., Chinoy, Hector, Agarwal, Vikas, Aggarwal, Rohit, Gupta, Latika, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Hoff LS] School of Medicine, Universidade Potiguar (UnP), Natal, Brazil. [Ravichandran N] Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. [Shinjo SK, Junior JG] Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. [Day J] Department of Rheumatology, Royal Melbourne Hospital, Parkville, Australia. Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. Department of Medical Biology, University of Melbourne, Parkville, Australia. [Sen P] Maulana Azad Medical College, 2-Bahadurshah Zafar Marg, New Delhi, India. [O'Callaghan AS] Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Malalties autoimmunitàries ,Autoimmune diseases ,Immunology ,Immune System Diseases::Autoimmune Diseases [DISEASES] ,enfermedades del sistema inmune::enfermedades autoinmunes [ENFERMEDADES] ,COVID-19 ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunoterapia activa::vacunación [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Breakthrough infection ,SARS-CoV-2 vaccination ,Rheumatology ,Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunotherapy, Active::Vaccination [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Immunology and Allergy ,Idiopathic inflammatory myopathies ,COVID-19 (Malaltia) - Vacunació - Abstract
Objectives We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). Methods This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. Results Among 10,900 respondents [42 (30–55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4–0.8, and OR = 0.3, 95% CI 0.2–0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2–5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3–5.3 in BI]. In a multivariate regression analysis, age 30–60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5–1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1–2.7). Conclusions Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.
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- 2023
26. Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis
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Isabella Annesi-Maesano, Nour Baïz, Jean-Claude Souberbielle, Patricia Dargent-Molina, John D. Wark, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Department of Medicine, University of Melbourne-The Royal Melbourne Hospital, Laboratoire de Physiologie, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), EDEN Mother-Child Cohort Study Group, Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), De Lauzon-Guillain, Blandine, Epidémiologie des Maladies Allergiques et Respiratoires ( EPAR ), Epidémiologie, systèmes d'information et modélisation, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP]-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), The Royal Melbourne Hospital-Université de Melbourne, and Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
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Male ,Pediatrics ,Allergy ,DC ,Cohort Studies ,0302 clinical medicine ,Pregnancy ,Surveys and Questionnaires ,Etude des Déterminants pré et post natals du développement et de la santé de l′Enfant ,Immunology and Allergy ,030212 general & internal medicine ,Vitamin D ,atopic dermatitis ,25(OH)D ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,OR ,Atopic dermatitis ,Odds ratio ,25-hydroxyvitamin D ,3. Good health ,Cord blood ,Child, Preschool ,cord blood ,Female ,Dendritic cell ,Adult ,Risk ,medicine.medical_specialty ,allergic diseases ,Cord ,Rhinitis, Allergic, Perennial ,Offspring ,Immunology ,mother-child cohort ,Dermatitis, Atopic ,03 medical and health sciences ,medicine ,Vitamin D and neurology ,Humans ,Asthma ,Respiratory Sounds ,EDEN ,business.industry ,wheezing ,Infant, Newborn ,Infant ,Immunoglobulin E ,medicine.disease ,Rhinitis, Allergic ,030228 respiratory system ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Follow-Up Studies - Abstract
BACKGROUND: There is increasing evidence of the effect of maternal vitamin D intake during pregnancy on the risk of asthma and allergic outcomes in offspring. However, studies on the relationship between cord levels of 25-hydroxyvitamin D (25[OH]D) and asthma and allergic diseases are very few. OBJECTIVE: Our aim was to investigate the associations between cord serum 25(OH)D levels and asthma, wheezing, allergic rhinitis, and atopic dermatitis in the offspring from birth to 5 years. METHODS: Cord blood samples were collected at birth and analyzed for 25(OH)D levels in 239 newborns from the Etude des Determinants pre et post natals du developpement et de la sante de l'Enfant (EDEN) birth cohort. The children were followed up until age 5 years by using International Study of Asthma and Allergies in Childhood-based symptom questionnaires. RESULTS: The median cord serum level of 25(OH)D was 17.8 ng/mL (interquartile range, 15.1 ng/mL). By using multivariable-adjusted logistic regression models, a significant inverse association was observed between cord serum 25(OH)D levels and risk of transient early wheezing and early- and late-onset atopic dermatitis, as well as atopic dermatitis, by the ages of 1, 2, 3, and 5 years. We found no association between cord serum 25(OH)D levels and asthma and allergic rhinitis at age 5 years. CONCLUSIONS: Cord serum 25(OH)D levels were inversely associated with the risk of transient early wheezing and atopic dermatitis by the age of 5 years, but no association was found with asthma and allergic rhinitis.
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- 2014
27. Treatment of Herpes Simplex Virus Type 2 Meningitis: A Survey Among Infectious Diseases Specialists in France, Sweden, Australia, and Denmark
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Jacob Bodilsen, Pierre Tattevin, Steven Y C Tong, Pontus Naucler, Henrik Nielsen, gomspace [Aalborg], Aalborg University Hospital, ESCMID [Basel], Pôle de Formation des Professionnels de Santé du Centre hospitalier de Rennes (PFPS), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Mercer Australia [Melbourne], The Royal Melbourne Hospital, University of Melbourne, Division of Infectious Diseases [Stockholm, Sweden] (Department of Medicine Solna), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], and None
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Infectious Diseases ,Oncology ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,meningitis ,survey ,trial ,HSV-2 ,management - Abstract
Background We aimed to describe attitudes toward treatment of herpes simplex virus type 2 (HSV-2) meningitis and prioritize future trials. Methods This was a self-administered online survey of HSV-2 meningitis treatment among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark. Results A total of 223 ID specialists (45% female) from France (36%), Denmark (24%), Sweden (21%), and Australia (19%) participated in the survey, primarily from university hospitals (64%). The estimated overall response rate was 11% and ranged from 6% (Australia) to 64% (Denmark). Intravenous (IV) acyclovir followed by oral valacyclovir was the favored treatment in 110 of 179 (61%), whereas monotherapy with either IV acyclovir or oral valacyclovir was used by 35 of 179 (20%) and 34 of 179 (19%), respectively. The median total duration was reported to be 7 days (interquartile range, 7–10 days) regardless of antiviral regimen. Immunocompromise influenced decisions on antiviral treatment in 110 of 189 (58%) of respondents, mainly by prolonged total duration of treatment (36/110 [33%]), prolonged IV administration (31/110 [28%]), and mandatory antiviral treatment (25/110 [23%]). Treatment with acyclovir/valacyclovir versus placebo and comparison of acyclovir versus valacyclovir were assigned the highest prioritization scores for future randomized controlled trials on HSV-2 meningitis. Conclusions Perceptions of indications for as well as type and duration of antiviral treatment varied substantially among ID specialists.
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- 2022
28. AUTOMATIC DETECTION OF SMALL SPHERICAL LESIONS USING MULTISCALE APPROACH IN 3D MEDICAL IMAGES
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Paul Yates, Christopher C. Rowe, Patricia Desmond, Fabrice Meriaudeau, Amir Fazlollahi, Pierrick Bourgeat, Victor L. Villemagne, Olivier Salvado, Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Nuclear Medicine, Austin Health-Centre for Positron Emission Tomography (PET)-Austin Hospital, The Mental Health Research Institute, University of Melbourne, Department of Medecine, University of Melbourne-Austin Health, Department of Radiology, Royal Melbourne Hospital, Melbourne University, VIC, Parkville, Australia, department of Radiology, Royal Melbourne Hospital-Royal Melbourne Hospital, CSIRO Information and Commuciation Technologies ( CSIRO ICT Centre ), Commonwealth Scientific and Industrial Research Organisation [Canberra] ( CSIRO ), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, 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, Austin Health-Centre for Positron Emission Tomography (PET)-Austin Hospital [Melbourne], Austin Health, CSIRO Information and Commuciation Technologies (CSIRO ICT Centre), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), and Meriaudeau, Fabrice
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Hessian matrix ,Ground truth ,Orientation (computer vision) ,business.industry ,02 engineering and technology ,Translation (geometry) ,Blob detection ,Object detection ,030218 nuclear medicine & medical imaging ,Scale space ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,[INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV] ,[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV] ,Line (geometry) ,[ INFO.INFO-TI ] Computer Science [cs]/Image Processing ,0202 electrical engineering, electronic engineering, information engineering ,symbols ,020201 artificial intelligence & image processing ,Computer vision ,Artificial intelligence ,business ,Mathematics - Abstract
International audience; Automated detection of small, low level shapes such as circular/spherical objects in images is a challenging computer vision problem. For many applications, especially microbleed detection in Alzheimer's disease, an automatic pre-screening scheme is required to identify potential seeds with high sensitivity and reasonable specificity. A new method is proposed to detect spherical objects in 3D medical images within the multi-scale Laplacian of Gaussian framework. The major contributions are (1) breaking down 3D sphere detection into 1D line profile detection along each coordinate dimension, (2) identifying center of structures by normalizing the line response profile and (3) employing eigenvalues of the Hessian matrix at optimum scale for the center points to determine spherical objects. The method is validated both on simulated data and susceptibility weighted MRI images with ground truth provided by a medical expert. Validation results demonstrate that the current approach has higher performance in terms of sensitivity and specificity and is effective in detecting adjacent microbleeds, with invariance to intensity, orientation, translation and object scale.
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- 2013
29. Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis
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Tobias Derfuss, Tomas Kalincik, Timothy Spelman, Maria Trojano, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, LUGARESI, ALESSANDRA, Raymond Hupperts, Edgardo Cristiano, Vincent Van Pesch, Francois Grand’Maison, Daniele La Spitaleri, Maria Edite Rio, Sholmo Flechter, Celia Oreja Guevara, Giorgio Giuliani, Aldo Savino, Maria Pia Amato, Thor Petersen, Ricardo Fernandez Bolanos, Roberto Bergamaschi, Gerardo Iuliano, Cavit Boz, Jeannette Lechner Scott, Norma Deri, Orla Gray, Freek Verheul, Marcela Fiol, Michael Barnett, Erik van Munster, Vetere Santiago, Fraser Moore, Mark Slee, Maria Laura Saladino, Raed Alroughani, Cameron Shaw, Krisztian Kasa, Tatjana Petkovska Boskova, Leontien den Braber Moerland, Joab Chapman, Eli Skromne, Joseph Herbert, Dieter Poehlau, Merrilee Needham, Elizabeth Alejandra Bacile Bacile, Walter Oleschko Arruda, Mark Paine, Bhim Singhal, Steve Vucic, Jose Antonio Cabrera Gomez, Helmut Butzkueven, MSBase Study Group, Klinische Neurowetenschappen, RS: MHeNs School for Mental Health and Neuroscience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Tobias Derfu, Tomas Kalincik, Timothy Spelman, Maria Trojano, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, Alessandra Lugaresi, Raymond Huppert, Edgardo Cristiano, Vincent Van Pesch, Francois Grand’Maison, Daniele La Spitaleri, Maria Edite Rio, Sholmo Flechter, Celia Oreja-Guevara, Giorgio Giuliani, Aldo Savino, Maria Pia Amato, Thor Petersen, Ricardo Fernandez-Bolano, Roberto Bergamaschi, Gerardo Iuliano, Cavit Boz, Jeannette Lechner-Scott, Norma Deri, Orla Gray, Freek Verheul, Marcela Fiol, Michael Barnett, Erik van Munster, Vetere Santiago, Fraser Moore, Mark Slee, Maria Laura Saladino, Raed Alroughani, Cameron Shaw, Krisztian Kasa, Tatjana Petkovska-Boskova, Leontien den Braber-Moerland, Joab Chapman, Eli Skromne, Joseph Herbert, Dieter Poehlau, Merrilee Needham, Elizabeth Alejandra Bacile Bacile, Walter Oleschko Arruda, Mark Paine, Bhim Singhal, Steve Vucic, Jose Antonio Cabrera-Gomez, Helmut Butzkueven, MSBase Study Group, The MSBase Study Group, [Karkincic,T, and Butzkueven,H] Departments of Medicine and Neurology, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. [Spelman,T] Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. [Trojano,M] Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. [Duquette,P] Hòpital Notre Dame, Montreal, Canada. [Izquierdo,G] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Grammond,P] Hotel-Dieu de Levis, Quebec, Canada. [Lugaresi,A] MS Center, Department of Neuroscience and Imaging, University ‘G. d’Annunzio’, Chieti, Italy. [Hupperts,R] Maaslandziekenhuis, Sittard, The Netherlands. [Cristiano,E] Hospital Italiano, Buenos Aires, Argentina. [Van Pesch,V] Cliniques Universitaires Saint-Luc, Brussels, Belgium. [Grand´Maison,F ]Neuro Rive-Sud, Hòpital Charles LeMoyne, Quebec, Canada. [La Spitaleri,D] AORN San Giuseppe Moscati, Avellino, Italy. [Rio,ME] Hospital S. Joao, Porto, Portugal. [Flechter,S] Assaf Harofeh Medical Center, Beer-Yaakov, Israel. [Oreja-Guevera,C] University Hospital San Carlos, IdISSC, Madrid, Spain. [Giuliani,G] Ospedale di Macerata, Macerata, Italy. [Savino,A] Consultorio Privado, Buenos Aires, Argentina. [Amato,MP] Department NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy. [Petersen,T] Kommunehospitalet, Aarhus C, Denmark. [Fernandez-Bolanos,R] Hospital Universitario Virgen de Valme, Seville, Spain. [Bergamaschi,R] Neurological Institute IRCCS Mondino, Pavia, Italy. [Iuliano,G] Ospedali Riuniti di Salerno, Salerno, Italy. [Boz,C] Karadeniz Technical University, Trabzon, Turkey. [Lechner-Scott,J] John Hunter Hospital, Newcastle, Australia. [Deri,N] Hospital Fernandez, Buenos Aires, Argentina.[Gray,O] Craigavon Area Hospital, Portadown, United Kingdom. [Verheul,F] Groen Hart Ziekenhuis, Gouda, The Netherlands. [Fiol,M] FLENI, Buenos Aires, Argentina. [Barnett,M] Brain and Mind Research Institute, Sydney, Australia. [van Munster,E] Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, The Netherlands. [Santiago,V]HIGA Gral, San Martin La Plata, Argentina. [Moore,F] Jewish General Hospital, McGill University, Montreal, Canada. [Slee,M] Flinders University and Medical Centre, Adelaide, Australia. [Saladino,ML] INEBA, Buenos Aires, Argentina. [Alroughani,R] Amiri Hospital, Kuwait City, Kuwait. [Shaw,C] Geelong Hospital, Geelong, Australia. [Kasa,K] Jahn Ferenc Teaching Hospital, Budapest, Hungary. [Petkovska-Boskova,T] Clinic of Neurology Clinical Center, Skopje, Macedonia. [den Braber-Moerland,L] Francicus Ziekenhuis, Roosendaal, The Netherlands. [Chapman,J] Sheba Medical Center, Tel Hashomer, Israel. [Skromne,E] Hospital Angeles Mexico City, Lomas, Mexico. [Herbert,J] New York University Hospital for Joint Diseases, New York, New York, United States of America. [Poehlau,D] Multiple Sclerosis Centre Kamillus-Klinik, Asbach, Germany. [Needham,M] Royal North Shore Hospital, Sydney, Australi. [Bacile Bacile,EA] Instituto de Neurociencias Cordoba, Cordoba, Argentin. [Arruda,WO] Hospital Ecoville, Curitiba, Brazil. [Paine, M] St Vincent’s Hospital, Melbourne, Australia. [Sighal,B] Bombay Hospital Institute of Medical Sciences, Mumbai, India. [Vucic,S] Westmead Hospital, Sydney, Australia. [Cabrera-Gomez,JA] Centro Internacional de Restauracion Neurologica, Havana, Cuba. [Butzkueven,H] Department of Neurology, Box Hill Hospital and Monash University, Melbourne, Australia.
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Male ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Withholding Treatment [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings] ,Kaplan-Meier Estimate ,law.invention ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Randomized controlled trial ,law ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Likelihood Functions [Medical Subject Headings] ,Longitudinal Studies ,Non-U.S. Gov't ,Espectroscopía de resonancia magnética ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings] ,Likelihood Functions ,Multidisciplinary ,Adulto ,Subcutaneous ,Research Support, Non-U.S. Gov't ,Statistics ,Drug Information ,Magnetic Resonance Imaging ,Clinical Trial ,Funciones de verosimilitud ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Reproducibility of Results [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Injections::Injections, Subcutaneous [Medical Subject Headings] ,Treatment Outcome ,Relación dosis-respuesta a droga ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interferons::Interferon Type I::Interferon-beta [Medical Subject Headings] ,Neurology ,Observational Studies ,Medicine ,Female ,Drug ,Interferon beta-1a ,Research Article ,medicine.drug ,Adult ,Drugs and Devices ,medicine.medical_specialty ,Multiple Sclerosis ,Clinical Research Design ,Science ,Injections, Subcutaneous ,Cumplimiento y adherencia al tratamiento ,Reproducibilidad de los resultados ,Check Tags::Male [Medical Subject Headings] ,Biostatistics ,Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings] ,Research Support ,Drug Administration Schedule ,Autoimmune Diseases ,Injections ,Medication Adherence ,Dose-Response Relationship ,Adverse Reactions ,Internal medicine ,Covariate ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,medicine ,Journal Article ,Humans ,Comparative Study ,Statistical Methods ,Adverse effect ,Propensity Score ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Demography ,Interferón beta ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings] ,Dose-Response Relationship, Drug ,business.industry ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Drug [Medical Subject Headings] ,Multiple sclerosis ,Reproducibility of Results ,Inyecciones subcutáneas ,multiple sclerosis drug therapy ,Interferon-beta ,medicine.disease ,Disciplines and Occupations::Social Sciences::Demography [Medical Subject Headings] ,Demyelinating Disorders ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Propensity Score [Medical Subject Headings] ,Clinical trial ,Check Tags::Female [Medical Subject Headings] ,Withholding Treatment ,Esclerosis múltiple ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior::Patient Compliance::Medication Adherence [Medical Subject Headings] ,Propensity score matching ,Clinical Immunology ,Observational study ,Resultado del tratamiento ,business ,Privación del tratamiento ,Mathematics - Abstract
Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVES To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. METHODS Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. RESULTS Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. CONCLUSIONS Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry. This study was funded by MSBase Foundation, a not-for-profit organisation. The MSBase Foundation receives financial support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer Schering and Sanofi Aventis. The study was also funded by Multiple Sclerosis Research Australia and MSAngels. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Yes
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- 2013
30. Enduring Effects of Early Life Stress on Firing Patterns of Hippocampal and Thalamocortical Neurons in Rats: Implications for Limbic Epilepsy
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Nigel C. Jones, Thomas Zheng, Christopher A. French, Patrick O'Brien, Michael R. Salzberg, Idrish Ali, Terence J. O'Brien, Gaurav Kumar, Margaret J. Morris, Didier Pinault, Department of Medicine, University of Melbourne-Royal Melbourne Hospital, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Department of Pharmacology, University of New South Wales [Sydney] (UNSW), Department of Psychiatry [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Department of Neurology, Royal Melbourne Hospital, NHMRC (Project Grants #566843), Pinault, Didier, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA)
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Male ,Anatomy and Physiology ,lcsh:Medicine ,Action Potentials ,Hippocampus ,Anxiety ,Hippocampal formation ,Epileptogenesis ,Behavioral Neuroscience ,0302 clinical medicine ,Thalamus ,Temporal Lobe Epilepsy ,Neural Pathways ,Neurobiology of Disease and Regeneration ,lcsh:Science ,Neurons ,0303 health sciences ,Thalamic reticular nucleus ,Multidisciplinary ,Age Factors ,Electroencephalography ,Animal Models ,medicine.anatomical_structure ,Neurology ,Social Isolation ,Medicine ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Research Article ,medicine.medical_specialty ,Neural Networks ,Clinical Research Design ,Limbic Lobe ,Neurophysiology ,Biology ,Amygdala ,Neurological System ,03 medical and health sciences ,Bursting ,Model Organisms ,Stress, Physiological ,Kindling, Neurologic ,medicine ,Animals ,Animal Models of Disease ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Rats, Wistar ,Psychiatry ,Electrodes ,030304 developmental biology ,Epilepsy ,Kindling ,lcsh:R ,Rats ,nervous system ,Cellular Neuroscience ,Rat ,lcsh:Q ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; : Early life stress results in an enduring vulnerability to kindling-induced epileptogenesis in rats, but the underlying mechanisms are not well understood. Recent studies indicate the involvement of thalamocortical neuronal circuits in the progression of kindling epileptogenesis. Therefore, we sought to determine in vivo the effects of early life stress and amygdala kindling on the firing pattern of hippocampus as well as thalamic and cortical neurons. Eight week old male Wistar rats, previously exposed to maternal separation (MS) early life stress or early handling (EH), underwent amygdala kindling (or sham kindling). Once fully kindled, in vivo juxtacellular recordings in hippocampal, thalamic and cortical regions were performed under neuroleptic analgesia. In the thalamic reticular nucleus cells both kindling and MS independently lowered firing frequency and enhanced burst firing. Further, burst firing in the thalamic reticular nucleus was significantly increased in kindled MS rats compared to kindled EH rats (p
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- 2013
31. 5- to 16-Year Follow-Up of 54 Consecutive Lateral Unicondylar Knee Arthroplasties With a Fixed-All Polyethylene Bearing
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Edouard Munini, Philippe Neyret, Camdon Fary, Sébastien Lustig, Ahmed ElGuindy, Guillaume Demey, Elvire Servien, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Orthopedic Departement, Faculty of Medecine, Fayoum University, The Royal Melbourne Hospital, and The Royal Melbourne Hospital, Department of Trauma Parkvilleand Orthopaedics
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Male ,musculoskeletal diseases ,medicine.medical_specialty ,Knee Joint ,Radiography ,Total knee arthroplasty ,Osteoarthritis ,Kaplan-Meier Estimate ,All polyethylene ,Prosthesis Design ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Longitudinal Studies ,Unicondylar Knee Arthroplasty ,Range of Motion, Articular ,Arthroplasty, Replacement, Knee ,Aged ,Retrospective Studies ,030222 orthopedics ,Bearing (mechanical) ,business.industry ,030229 sport sciences ,Recovery of Function ,Osteoarthritis, Knee ,[SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph] ,medicine.disease ,musculoskeletal system ,Surgery ,Treatment Outcome ,Polyethylene ,Female ,Implant ,business ,Range of motion ,Knee Prosthesis ,human activities ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies - Abstract
The clinical and radiographic results of 54 knees (52 patients) with a unicondylar knee arthroplasty (UKA) with fixed-all polyethylene bearing implanted for lateral osteoarthritis were studied at 5- to 16-year follow-up (mean, 100.9 months). Four underwent second surgery: 1 conversion to total knee arthroplasty and 3 received UKA in the medial compartment. The mean International Knee Society knee score was 94.9 points, with a mean range of motion of 132.6° and a mean International Knee Society function score totaling 81.8 points. Implant survival was 98.08%at 10 years. These excellent results suggest that UKA with fixed-all polyethylene bearing is a reliable option for management of isolated lateral knee osteoarthritis. Keywords: knee, unicompartmental arthroplasty, lateral osteoarthritis.
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- 2011
32. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis
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Lefort, M, Sharmin, S, Andersen, J B, Vukusic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, De Sèze, J, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun-Frenay, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanché, J P, Maurousset, A, Ben Nasr, H, Hankiewicz, K, Pottier, C, Maubeuge, N, Dimitri-Boulos, D, Nifle, C, Laplaud, D A, Horakova, D, Havrdova, E K, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Grand'Maison, F, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Shaygannejad, V, Prevost, J, Maimone, D, Skibina, O, Buzzard, K, Van der Walt, A, Karabudak, R, Van Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Koch-Henriksen, N, Sellebjerg, F, Soerensen, P S, Hilt Christensen, C. C., Rasmussen, P V, Jensen, M B, Frederiksen, J L, Bramow, S, Mathiesen, H K, Schreiber, K I, Butzkueven, H, Magyari, M, Kalincik, T, Leray, E, Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], University of Melbourne, Copenhagen University Hospital, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), i-SEP (i-SEP), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Saint-Antoine [AP-HP], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHI Poissy-Saint-Germain, CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Monash University [Melbourne], The Royal Melbourne Hospital, École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), OFSEP was supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche', within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. ML has recieved travel grant from ARSEP foundation for this project. The Clinical Outcomes Research unit at the University of Melbourne received funding from NHMRC (grant number 1140766, 1129789, and 1157717) to support this study. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva Pharmaeutical Industries and Sanofi Genzyme. The Danish Multiple Sclerosis Registry did not receive any funding to collaborate in this study., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de 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), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Rennes (UNIV-RENNES), Bramow, Stephan/0000-0001-9482-1771, Sellebjerg, Finn/0000-0002-1333-9623, Heinzlef, O., Camdessanche, J. P., Turkoglu, R., Boz, C., Shaygannejad, V, Moreau, T., Sellebjerg, F., Onofrj, M., De Seze, J., Wahab, A., VAN WIJMEERSCH, Bart, Mathiesen, H. K., Bramow, S., Andersen, J. B., Zephir, H., Ben Nasr, H., Ciron, J., Al-Khedr, A., Granella, F., Spitaleri, D., Lebrun-Frenay, C., Ferraro, D., Trojano, M., Labauge, P., Thouvenot, E., Skibina, O., Magyari, M., Patti, F., Maimone, D., Kalincik, T., Buzzard, K., Dimitri-Boulos, D., Alroughani, R., Maillart, E., Koch-Henriksen, N., Hankiewicz, K., Rasmussen, P., V, Jensen, M. B., Lechner-Scott, J., Csepany, T., Casez, O., Soerensen , P. S., Lugaresi, A., McCombe, P., Defer, G., Terzi, M., Christensen, C. C. Hilt, Girard, M., Ruet, A., Berger , E., Maurousset, A., Duquette, P., Horakova, D., Laplaud, D. A., Casey, R., Edan, G., Schreiber, K., I, Lefort, M., Cabre, P., Maubeuge, N., Grammond, P., Prevost, J., Havrdova, E. K., Gout, O., Prat, A., Sola, P., Slee, M., Sharmin , S., Leray, E., Ozakbas, S., Grand'Maison, F., Montcuquet, A., Nifle, C., Eichau, S., Butzkueven, H., Karabudak, R., Vukusic, S., Debouverie, M., Clavelou, P., Stankoff, B., Pottier, C., Yamout, B., Vucic, S., Van der Walt, A., Pelletier, J., Bourre, B., Izquierdo, G., Frederiksen, J. L., Lefort, M, Sharmin, S, Andersen, J B, Vukusic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, De Sèze, J, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun-Frenay, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanché, J P, Maurousset, A, Ben Nasr, H, Hankiewicz, K, Pottier, C, Maubeuge, N, Dimitri-Boulos, D, Nifle, C, Laplaud, D A, Horakova, D, Havrdova, E K, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Grand'Maison, F, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Prevost, J, Maimone, D, Skibina, O, Buzzard, K, Van der Walt, A, Karabudak, R, Van Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Koch-Henriksen, N, Sellebjerg, F, Soerensen, P S, Hilt Christensen, C C, Rasmussen, P V, Jensen, M B, Frederiksen, J L, Bramow, S, Mathiesen, H K, Schreiber, K I, Butzkueven, H, Magyari, M, Kalincik, T, and Leray, E
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MESH: Fingolimod Hydrochloride ,Indication bias ,Multiple Sclerosis ,MESH: Multiple Sclerosis, Relapsing-Remitting ,Propensity score ,Epidemiology ,Positivity assumption ,[SDV]Life Sciences [q-bio] ,Health Informatics ,Effectiveness ,Multiple sclerosis ,Multiple Sclerosis, Relapsing-Remitting ,Multiple Sclerosi ,Humans ,Fingolimod Hydrochloride/therapeutic use ,MESH: Treatment Outcome ,Censoring ,Natalizumab/therapeutic use ,MESH: Humans ,Fingolimod Hydrochloride ,Natalizumab ,Effectivene ,Causal contrasts ,MESH: Natalizumab ,MESH: Multiple Sclerosis ,Multiple Sclerosis, Relapsing-Remitting/drug therapy ,Causal contrast ,Treatment Outcome ,Multiple Sclerosis/drug therapy ,Indication bia ,Human - Abstract
Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled. OFSEP was supported by a grant provided by the French State and handled by the "Agence Nationale de la Recherche", within the framework of the "Investments for the Future" program, under the reference ANR10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. ML has recieved travel grant from ARSEP foundation for this project. The Clinical Outcomes Research unit at the University of Melbourne received funding from NHMRC (grant number
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- 2022
33. The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study
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Roberts, Jason, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, de Waele, Jan, Deans, Renae, Eastwood, Glenn, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios, Lassig-Smith, Melissa, Laterre, Pierre-Francois, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne, Rello, Jordi, Roberts, Darren, Roberts, Michael, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi, Paul, Sanjoy, Lipman, Jeffrey, Andresen, Max, Baltazar, Sónia, Barbar, Saber, Costa, Eulália, Durand, Dominique, Freitas, Ricardo, Frey, Otto, Guerra Valero, Yarmarly, Haughton, Margaret, Koeberer, Andreas, Kollef, Marin, Klein, Kerenaftali, Mehta, Ravindra, Mckenzie, Cathy, Muller, Laurent, Nair, Priya, Nayyar, Vineet, Ordóñez Mejia, Jenny, Panagou, Georgia-Laura, Paxton, Jody, Peck, Leah, Samanta, Mayukh, Vincent, Jean-Louise, Wan, Ruth, Young, Helen, University of Southern Queensland (USQ), Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Princess Alexandra Hospital, Brisbane, SMARRT Study, ANZICS Clinical Trials Group, The Chinese University of Hong Kong [Hong Kong], Austin Hospital [Melbourne], Austin Health, The Ottawa Hospital, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Westmead Hospital [Sydney], The University of Sydney, The Queen Elizabeth Hospital (TQEH), University of Adelaide, Monash University [Melbourne], Royal Darwin Hospital, Flinders University [Adelaide, Australia], National Critical Care and Trauma Response Centre (Darwin) (NCCTRC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Corporació Sanitària Parc Taulí, Barcelona Biomedical Research Park (PRBB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, QIMR Berghofer Medical Research Institute, Centro Hospitalar e Universitário [Coimbra], Athens Naval Hospital, University of Queensland [Brisbane], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Kliniken Landkreis Heidenheim, Melbourne EpiCentre, The Royal Melbourne Hospital, Hospital Clínic de Barcelona (ICMiD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Nepean Hospital, Ghent University Hospital, Universidad de Santiago de Chile [Santiago] (USACH), University of Sydney and Nepean Hospital, Hospital Tengku Ampuan Afzan (HTAA), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital of Ioannina, Royal Brisbane & Women's Hospital, Cliniques universitaires St Luc [Bruxelles], Guy's and St Thomas' Hospital [London], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universitat Internacional de Catalunya [Barcelona] (UIC), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, International Islamic University Malaysia [Kuala Lumpur], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of South Australia [Adelaide], Basil Hetzel Institute (BHI), Translational Research Institute (TRI), Gold Coast University Hospital, University Hospital of Tarragona 'Joan XXIII', University Rovirai Virgili de Tarragona (URV), Ochsner Medical Center, The Queen Elizabeth Hospital, Hospital Clínic de Barcelona, Roberts, Jason A., Joynt, Gavin M., Lee, Anna, Choi, Gordon, Roberts, Michael S., Sinnollareddy, Mahipal, and Lipman, Jeffrey
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0301 basic medicine ,Continuous renal replacement therapy ,medicine.medical_treatment ,continuous renal replacement therapy ,Antibiotics ,urologic and male genital diseases ,MESH: Meropenem ,030226 pharmacology & pharmacy ,law.invention ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,law ,Prospective Studies ,pharmacokinetic ,extended daily dialysis ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Extended daily dialysis ,Intensive care unit ,Anti-Bacterial Agents ,3. Good health ,Renal Replacement Therapy ,Infectious Diseases ,MESH: Critical Illness ,Vancomycin ,beta-lactam ,medicine.drug ,MESH: Piperacillin ,Microbiology (medical) ,medicine.medical_specialty ,medicine.drug_class ,Critical Illness ,Beta-lactam ,030106 microbiology ,Pharmacokinetic ,Meropenem ,03 medical and health sciences ,MESH: Anti-Bacterial Agents ,Internal medicine ,Intensive care ,medicine ,Humans ,Trough Concentration ,Dosing ,Renal replacement therapy ,Piperacillin ,MESH: Humans ,business.industry ,MESH: Prospective Studies ,renal clearance ,MESH: Renal Replacement Therapy ,business ,Renal clearance - Abstract
Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
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- 2020
34. Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity
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Steve Simpson-Yap, Ashkan Pirmani, Tomas Kalincik, Edward De Brouwer, Lotte Geys, Tina Parciak, Anne Helme, Nick Rijke, Jan A. Hillert, Yves Moreau, Gilles Edan, Sifat Sharmin, Tim Spelman, Robert McBurney, Hollie Schmidt, Arnfin B. Bergmann, Stefan Braune, Alexander Stahmann, Rod M. Middleton, Amber Salter, Bruce Bebo, Anneke Van der Walt, Helmut Butzkueven, Serkan Ozakbas, Cavit Boz, Rana Karabudak, Raed Alroughani, Juan I. Rojas, Ingrid A. van der Mei, Guilherme Sciascia do Olival, Melinda Magyari, Ricardo N. Alonso, Richard S. Nicholas, Anibal S. Chertcoff, Ana Zabalza de Torres, Georgina Arrambide, Nupur Nag, Annabel Descamps, Lars Costers, Ruth Dobson, Aleisha Miller, Paulo Rodrigues, Vesna Prčkovska, Giancarlo Comi, Liesbet M. Peeters, Institut Català de la Salut, [Simpson-Yap S] CORe, Department of Medicine, and Neuroepidemiology Unit, Melbourne School of Population & Global Health, The University of Melbourne, Menzies Institute for Medical Research, University of Tasmania, Australia. [Pirmani A, Geys L, Parciak T] ESAT-STADIUS, KU Leuven, Biomedical Research Institute–Data Science Institute, Hasselt University, Belgium. [Kalincik T] CORe, Department of Medicine, The University of Melbourne, MS Centre, Department of Neurology, Royal Melbourne Hospital, Australia. [De Brouwer E] ESAT-STADIUS, KU Leuven, Belgium. [Zabalza de Torres A, Arrambide G] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,Multiple Sclerosis ,COVID-19 (Malaltia) - Factors de risc ,Clinical Neurology ,Esclerosi múltiple ,técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Risk Factors ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Humans ,Science & Technology ,Information Dissemination ,Natalizumab ,Neurosciences ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES] ,COVID-19 ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,Glatiramer Acetate ,Multiple Sclerosis, Chronic Progressive ,Antigens, CD20 ,Neurology ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] ,Neurology (clinical) ,Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Neurosciences & Neurology ,Rituximab ,Life Sciences & Biomedicine ,Immunosuppressive Agents - Abstract
Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19. BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.
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- 2022
35. Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation
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Marine Gros, Elodie Segura, Derek C. Rookhuizen, Blandine Baudon, Sandrine Heurtebise-Chrétien, Nina Burgdorf, Mathieu Maurin, Eugene A. Kapp, Richard J. Simpson, Patrycja Kozik, Jose A. Villadangos, Mathieu J.M. Bertrand, Marianne Burbage, Sebastian Amigorena, AMIGORENA, Sebastian, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, University of Melbourne, La Trobe University [Melbourne], MRC Laboratory of Molecular Biology [Cambridge, UK] (LMB), University of Cambridge [UK] (CAM)-Medical Research Council, and Universiteit Gent = Ghent University (UGENT)
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EXPRESSION ,ESCRT-III ,[SDV]Life Sciences [q-bio] ,PROTEIN ,necroptosis ,CD8(+) DENDRITIC CELLS ,General Biochemistry, Genetics and Molecular Biology ,Cross-Priming ,Cytosol ,Medicine and Health Sciences ,dendritic cells ,Antigens ,MINOR H-ANTIGENS ,NECROPTOSIS ,cross-presentation ,RELEASE ,Antigen Presentation ,Endosomal Sorting Complexes Required for Transport ,EXOGENOUS ANTIGENS ,Biology and Life Sciences ,CP: Immunology ,TRANSLOCATION ,endomembrane disruption ,MHC CLASS-I ,[SDV] Life Sciences [q-bio] ,membrane repair ,T-CELLS ,CP: Cell biology - Abstract
International audience; Despite its crucial role in initiation of cytotoxic immune responses, the molecular pathways underlying antigen cross-presentation remain incompletely understood. The mechanism of antigen exit from endocytic compartments into the cytosol is a long-standing matter of controversy, confronting two main models: transfer through specific channels/transporters or rupture of endocytic membranes and leakage of luminal content. By monitoring the occurrence of intracellular damage in conventional dendritic cells (cDCs), we show that cross-presenting cDC1s display more frequent endomembrane injuries and increased recruitment of endosomal sorting complex required for transport (ESCRT)-III, the main repair system for intracellular membranes, relative to cDC2s. Silencing of CHMP2a or CHMP4b, two effector subunits of ESCRT-III, enhances cytosolic antigen export and cross-presentation. This phenotype is partially reversed by chemical inhibition of RIPK3, suggesting that endocytic damage is related to basal activation of the necroptosis pathway. Membrane repair therefore proves crucial in containing antigen export to the cytosol and cross-presentation in cDCs.
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- 2022
36. High and low efficacy therapy in secondary progressive multiple sclerosis
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Roos, I., Leray, E., Buzzard, K., Skibina, O., Lechner-Scott, J., Malpas, C. B., Butzkueven, H., Vukusic, S, Kalincik, T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Monash university, The Royal Melbourne Hospital, University of Newcastle [Callaghan, Australia] (UoN), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hospices Civils de Lyon (HCL)
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[SDV]Life Sciences [q-bio] - Abstract
International audience; Meeting Abstract
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- 2022
37. Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV
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Graham S Cooke, Adeeba Kamarulzaman, Margaret Hellard, Jürgen K. Rockstroh, Kenneth H. Mayer, Georg M. N. Behrens, Denise Naniche, Nikos Dedes, Ricardo Baptista Leite, Jeffrey V. Lazarus, David Serwadda, Sanjay Bhagani, María José Fuster-Ruiz de Apodaca, Laura Waters, Shabbar Jaffar, Carlos F. Caceres, Diana Romero, Peter Reiss, Richard Elliott, Susan Buchbinder, Pedro Cahn, Richard Harding, Julia del Amo, Reena Rajasuriar, Teymur Noori, Kelly Safreed-Harmon, Antonella d'Arminio Monforte, Timothy B. Hallett, Jane Anderson, Wafaa El-Sadr, Darren L. Brown, Marina B. Klein, Doreen Moraa, Sharon R Lewin, Nesrine Rizk, Denis Nash, Giovanni Guaraldi, Graham Brown, Anton Pozniak, Georgina Caswell, Caroline A. Sabin, Linda-Gail Bekker, Patrizia Carrieri, Meaghan Kall, José Antonio Pérez-Molina, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), University of Malaya [Kuala Lumpur, Malaisie], Homerton University Hospital, Portuguese National Parliament [Lisbon, Portugal] (PNP), Medizinische Hochschule Hannover (MHH), The Desmond Tutu HIV Centre [Cape Town, South Africa], University College of London [London] (UCL), Chelsea and Westminster NHS Foundation Trust [London, UK], University of New South Wales [Sydney] (UNSW), San Francisco Department of Public Health [San Francisco, CA, USA] (SFDPH), Universidad Peruana Cayetano Heredia (UPCH), Fundación Huésped [Buenos Aires], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Global Network of People Living with HIV (GNP+) [Cape Town, South Africa], Imperial College London, University of Milan, Positive Voice [Athens, Greece] (PV), Ministerio de Sanidad/Ministry of Health [Madrid, Spain], HIV Legal Network [Toronto, ON, Canada], Columbia University [New York], Universidad Nacional de Educación a Distancia (UNED), Università degli Studi di Modena e Reggio Emilia (UNIMORE), King‘s College London, Burnet Institute [Melbourne, Victoria], Liverpool School of Tropical Medicine (LSTM), Public Health England [London], McGill University Health Center [Montreal] (MUHC), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Monash University [Melbourne], Harvard Medical School [Boston] (HMS), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), ESA YOUTH 2030 [Nairobi, Kenya], City University of New York [New York] (CUNY), European Centre for Disease Prevention and Control (ECDC), London School of Hygiene and Tropical Medicine (LSHTM), University of Amsterdam [Amsterdam] (UvA), American University of Beirut [Beyrouth] (AUB), University Hospital Bonn, Makerere University [Kampala, Ouganda] (MAK), Central and North West London NHS Foundation Trust [London, UK], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Malbec, Odile, Ministerio de Sanidad / Ministry of Health [Madrid, Spain], European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), and Medical Research Council (MRC)
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Gerontology ,SYMPTOMS ,Social stigma ,STIGMA REDUCTION ,IMPACT ,[SDV]Life Sciences [q-bio] ,Social Stigma ,General Physics and Astronomy ,wc_503 ,HIV Infections ,Disease ,Comorbidity ,DISEASE ,Comorbidities ,socioeconomic conditions ,0302 clinical medicine ,ANTIRETROVIRAL THERAPY ,QUALITY-OF-LIFE ,Surveys and Questionnaires ,Health care ,Medicine ,030212 general & internal medicine ,RISK ,Multidisciplinary ,human immunodeficiency virus ,030503 health policy & services ,Health services ,3. Good health ,Multidisciplinary Sciences ,[SDV] Life Sciences [q-bio] ,HUMAN-IMMUNODEFICIENCY-VIRUS ,Perspective ,Science & Technology - Other Topics ,0305 other medical science ,Adult ,Quality of life ,wc_503_2 ,Consensus ,Science ,Stigma (botany) ,VALIDATION ,General Biochemistry, Genetics and Molecular Biology ,long-term change ,03 medical and health sciences ,Quality of life (healthcare) ,Acquired immunodeficiency syndrome (AIDS) ,Humans ,Science & Technology ,business.industry ,General Chemistry ,CARE ,medicine.disease ,Mental health ,quality of life ,Well-being ,Morbidity ,business ,Delivery of Health Care - Abstract
Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.
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- 2021
38. Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
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Brianna L. Kline, Sylvie Jaillard, Katrina M. Bell, Shabnam Bakhshalizadeh, Gorjana Robevska, Jocelyn van den Bergen, Jérôme Dulon, Katie L. Ayers, John Christodoulou, Michel C. Tchan, Philippe Touraine, Andrew H. Sinclair, Elena J. Tucker, Murdoch Children's Research Institute (MCRI), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), The Royal Melbourne Hospital, University of Melbourne, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Westmead Hospital [Sydney]
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mitochondrial disease ,mitochondrial ribosome ,Perrault syndrome ,premature ovarian insufficiency ,[SDV]Life Sciences [q-bio] ,MRPS7 ,Genetics ,ovarian dysfunction ,Genetics (clinical) - Abstract
International audience; The mitochondrial ribosome is critical to mitochondrial protein synthesis. Defects in both the large and small subunits of the mitochondrial ribosome can cause human disease, including, but not limited to, cardiomyopathy, hypoglycaemia, neurological dysfunction, sensorineural hearing loss and premature ovarian insufficiency (POI). POI is a common cause of infertility, characterised by elevated follicle-stimulating hormone and amenorrhea in women under the age of 40. Here we describe a patient with POI, sensorineural hearing loss and Hashimoto’s disease. The co-occurrence of POI with sensorineural hearing loss indicates Perrault syndrome. Whole exome sequencing identified two compound heterozygous variants in mitochondrial ribosomal protein 7 (MRPS7), c.373Aandgt;T/p.(Lys125*) and c.536Gandgt;A/p.(Arg179His). Both novel variants are predicted to be pathogenic via in-silico algorithms. Variants in MRPS7 have been described only once in the literature and were identified in sisters, one of whom presented with congenital sensorineural hearing loss and POI, consistent with our patient phenotype. The other affected sister had a more severe disease course and died in early adolescence due to liver and renal failure before the reproductive phenotype was known. This second independent report validates that variants in MRPS7 are a cause of syndromic POI/Perrault syndrome. We present this case and review the current evidence supporting the integral role of the mitochondrial ribosome in supporting ovarian function.
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- 2022
39. Effects of High and Low Efficacy Therapy in Secondary Progressive Multiple Sclerosis
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Katherine Buzzard, Dana Horáková, Guillermo Izquierdo, P. Grammond, S. Ozakbas, Francesco Patti, C. Boz, Tomas Kalincik, Francois Grand'Maison, Gilles Edan, E. K. Havrdova, Izanne Roos, Charles B Malpas, Ofsep Study Groups, Helmut Butzkueven, Jeannette Lechner-Scott, Jonathan Ciron, Sandra Vukusic, Emmanuelle Leray, Jean Pelletier, Sara Eichau Madueno, Oliver Gerlach, Pierre Clavelou, Olga Skibina, Marc Debouverie, Romain Casey, Maria Pia Amato, University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, First Faculty of Medicine Charles University [Prague], Hospital Universitario Virgen Macarena [Seville, Spain], Università degli studi di Catania [Catania], CHU Pontchaillou [Rennes], Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Hôpital de la Timone [CHU - APHM] (TIMONE), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), CHU Clermont-Ferrand, The Royal Melbourne Hospital, Monash University [Melbourne], CHU Toulouse [Toulouse], Zuyderland Hospital [Heerlen, The Netherlands], University of Newcastle [Australia] (UoN), Hospital Universitario Virgen Macarena [Séville], Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Catania = University of Catania (Unict), Università degli Studi di Firenze = University of Florence (UniFI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and University of Newcastle [Callaghan, Australia] (UoN)
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Oncology ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Multiple sclerosis ,03 medical and health sciences ,chemistry.chemical_compound ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,Natalizumab ,Internal medicine ,Teriflunomide ,medicine ,Humans ,030212 general & internal medicine ,Glatiramer acetate ,Secondary progressive multiple sclerosis (SPMS) ,business.industry ,Hazard ratio ,Glatiramer Acetate ,Multiple Sclerosis, Chronic Progressive ,medicine.disease ,Fingolimod ,3. Good health ,chemistry ,Alemtuzumab ,Ocrelizumab ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ObjectiveTo compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag.MethodsPatients treated with high-efficacy (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon beta, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP), 2 large observational cohorts. Therapeutic lag was estimated for each patient from their demographic and clinical characteristics. Propensity score was used to match patients treated with high- and low-efficacy therapies. Outcomes after the period of therapeutic lag was disregarded were compared in paired, pairwise-censored analyses.ResultsOne thousand patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7,p= 0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR 0.8,p= 0.39). No evidence for a difference in the risk of disability progression was observed.ConclusionIn treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active but not those with inactive SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group.Classification of EvidenceThis study provides Class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS, although we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.
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- 2021
40. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections—endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)
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Blomstrom-Lundqvist, C., Traykov, V., Erba, P. A., Burri, H., Nielsen, J. C., Bongiorni, M. G., Poole, J., Boriani, G., Costa, R., Deharo, J. -C., Epstein, L. M., Saghy, L., Snygg-Martin, U., Starck, C., Tascini, C., Strathmore, N., Kalarus, Z., Boveda, S., Dagres, N., Rinaldi, C. A., Biffi, M., Geller, L., Sokal, A., Birgersdotter-Green, U., Lever, N., Tajstra, M., Kutarski, A., Rodriguez, D. A., Hasse, B., Zinkernagel, A., Mangoni, E., Uppsala Universitet [Uppsala], Tokuda Hospital Sofia, University of Pisa - Università di Pisa, University Medical Center Groningen [Groningen] (UMCG), Aarhus University Hospital, Biorobotics Lab (University of Washington), University of Washington [Seattle], Università degli Studi di Modena e Reggio Emilia, Universidade Paulista [São Paulo] (UNIP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Cardiologie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Hofstra University [Hempstead], University of Szeged [Szeged], Department of Image Processing and Computer Graphics [Univ Szeged], University of Gothenburg (GU), West German Heart Center, Universität Duisburg-Essen [Essen], University Parthenope of Naples, The Royal Melbourne Hospital, Clinical sciences, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università degli Studi di Napoli 'Parthenope' = University of Naples (PARTHENOPE), Blomstrom-Lundqvist, C, Traykov, V, Erba, P, Burri, H, Nielsen, J, Bongiorni, M, Poole, J, Boriani, G, Costa, R, Deharo, J, Epstein, L, Saghy, L, Snygg-Martin, U, Starck, C, Tascini, C, Strathmore, N, Kalarus, Z, Boveda, S, Dagres, N, Rinaldi, C, Biffi, M, Geller, L, Sokal, A, Birgersdotter-Green, U, Lever, N, Tajstra, M, Kutarski, A, Rodriguez, D, Hasse, B, Zinkernagel, A, and Mangoni, E
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Leads ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Extraction ,030204 cardiovascular system & hematology ,law.invention ,Defibrillator ,0302 clinical medicine ,Randomized controlled trial ,law ,Health care ,Cardiac and Cardiovascular Systems ,Endocarditi ,03.02. Klinikai orvostan ,030212 general & internal medicine ,Antibiotic prophylaxis ,Cardiac resynchronization therapy ,Device ,Pacemaker ,Infection ,Kardiologi ,Re-implantation ,Endocarditis ,Latin America/epidemiology ,Cardiac implantable electronic device ,TRANSVENOUS LEAD EXTRACTION ,Defibrillators, Implantable/adverse effects ,Thoracic Surgery ,General Medicine ,STAPHYLOCOCCUS-AUREUS BACTEREMIA ,F-18-FDG PET/CT ,Defibrillators, Implantable ,SINGLE-CENTER EXPERIENCE ,3. Good health ,Cardiac implantable electronic devices ,EHRA consensus document ,Implantable cardioverter-defibrillators ,Microbiology ,Pacemakers ,Cardiothoracic surgery ,Risk assessment ,Cardiology and Cardiovascular Medicine ,EHRA Position Paper ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Asia ,Consensus ,PERMANENT PACEMAKER IMPLANTATION ,CARDIOVERTER-DEFIBRILLATOR IMPLANTATION ,Infections ,Communicable Diseases ,Implantable cardioverter-defibrillator ,03 medical and health sciences ,LONG-TERM COMPLICATIONS ,ANTIBIOTIC-PROPHYLAXIS ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Infections/diagnosis ,Physiology (medical) ,medicine ,Humans ,Intensive care medicine ,SURGICAL-SITE ,business.industry ,Cardiac Resynchronization Therapy Devices ,Latin America ,Lead ,RISK-FACTORS ,Artificial cardiac pacemaker ,Surgery ,Electronics ,Implantable cardioverterdefibrillators ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections. This article is simultaneously published also in Eur J Cardiothorac Surg. (https://doi.org/10.1093/ejcts/ezz296) and European Heart Journal (https://doi.org/10.1093/eurheartj/ehaa010). Minor differences in style may appear in each publication, but the article is substantially the same in each journal.
- Published
- 2019
41. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies
- Author
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Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (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 chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-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 Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-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), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, 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 Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,Tachycardia ,medicine.medical_specialty ,implantable ,Accurate estimation ,Ventricular Tachyarrhythmias ,Validation Studies as Topic ,030204 cardiovascular system & hematology ,tachycardia ,Sudden death ,LMNA ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,death ,Physiology (medical) ,Internal medicine ,defibrillators ,medicine ,Humans ,In patient ,030212 general & internal medicine ,sudden ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Prediction score ,business.industry ,Defibrillators, Implantable ,ventricular ,Tachycardia, Ventricular ,Cardiology ,Female ,medicine.symptom ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
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- 2019
42. Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial
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Ellen Ingalla, Deepak Sampath, Franck Morschhauser, Kylie D. Mason, Guillaume Cartron, Martine E.D. Chamuleau, Arijit Sinha, Divya Samineni, Edith Szafer-Glusman, Constantine S. Tam, Carla Casulo, Andre Goy, Pieternella J. Lugtenburg, Christian Klein, Steven Le Gouill, Adam M. Petrich, Mehrdad Mobasher, Andrew D. Zelenetz, Gilles Salles, Hervé Tilly, Sylvia Herter, Martin Kornacker, Laurie H. Sehn, Hematology, CCA - Cancer Treatment and quality of life, Memorial Sloane Kettering Cancer Center [New York], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), The Royal Melbourne Hospital, University of Rochester Medical Center (URMC), Centre hospitalier universitaire de Nantes (CHU Nantes), BC Cancer Agency (BCCRC), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), VU University Medical Center [Amsterdam], Hackensack University Medical Center [Hackensack], University of Melbourne, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Abbvie Inc. [North Chicago], Roche Products Ltd, Genentech, Inc. [San Francisco], Roche Innovation Center Zurich, Genentech, Inc., F. Hoffmann-La Roche [Basel], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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Male ,Oncology ,Follicular lymphoma ,CHOP ,MESH: Antineoplastic combined chemotherapy protocols/therapeutic use ,Bridged bicyclo compounds, Heterocyclic/therapeutic use ,Lymphoma, Non-Hodgkin/drug therapy ,Sulfonamides/therapeutic use ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Obinutuzumab ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,B-cell lymphoma ,Sulfonamides ,0303 health sciences ,Lymphoma, Non-Hodgkin ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Middle Aged ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,Vincristine ,030220 oncology & carcinogenesis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Rituximab ,medicine.drug ,medicine.medical_specialty ,Maximum Tolerated Dose ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antibodies, Monoclonal, Humanized ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Cyclophosphamide ,Aged ,030304 developmental biology ,business.industry ,Venetoclax ,Cell Biology ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,chemistry ,Doxorubicin ,Prednisone ,business ,Diffuse large B-cell lymphoma - Abstract
Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2+ and MYC+) DLBCL patients (87.5%; n = 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study. This trial was registered at www.clinicaltrials.gov as #NCT02055820.
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- 2019
43. Nociceptive sensory neurons promote CD8 T cell responses to HSV-1 infection
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Filtjens, Jessica, Roger, Anais, Quatrini, Linda, Wieduwild, Elisabeth, Gouilly, Jordi, Hoeffel, Guillaume, Rossignol, Rafaëlle, Daher, Clara, Debroas, Guilhaume, Henri, Sandrine, Jones, Claerwen M., Malissen, Bernard, Mackay, Laura K., Moqrich, Aziz, Carbone, Francis R., Ugolini, Sophie, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE16-0020,Myochronic,Etude des mécanismes moléculaires qui sous-tendent la chronicisation de la douleur. Ce qu'une Myosine non conventionnelle nous apprend(2017), Melbourne Law School [Melbourne], University of Melbourne, Centre d'Immunophénomique (CIPHE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
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Mice, Knockout ,Sensory Receptor Cells ,viruses ,Science ,[SDV]Life Sciences [q-bio] ,Neuroimmunology ,Herpes Simplex ,Mice, Transgenic ,Herpesvirus 1, Human ,Antimicrobial responses ,CD8-Positive T-Lymphocytes ,Article ,Nociceptive Pain ,Mice, Inbred C57BL ,NAV1.8 Voltage-Gated Sodium Channel ,Neutrophil Infiltration ,Animals ,Cytokines ,Humans ,Female ,Sensory processing ,CD8-positive T cells ,Skin - Abstract
Host protection against cutaneous herpes simplex virus 1 (HSV-1) infection relies on the induction of a robust adaptive immune response. Here, we show that Nav1.8+ sensory neurons, which are involved in pain perception, control the magnitude of CD8 T cell priming and expansion in HSV-1-infected mice. The ablation of Nav1.8-expressing sensory neurons is associated with extensive skin lesions characterized by enhanced inflammatory cytokine and chemokine production. Mechanistically, Nav1.8+ sensory neurons are required for the downregulation of neutrophil infiltration in the skin after viral clearance to limit the severity of tissue damage and restore skin homeostasis, as well as for eliciting robust CD8 T cell priming in skin-draining lymph nodes by controlling dendritic cell responses. Collectively, our data reveal an important role for the sensory nervous system in regulating both innate and adaptive immune responses to viral infection, thereby opening up possibilities for new therapeutic strategies., Herpes simplex virus 1 (HSV-1) is a neurotropic virus that often cause pain via the induction of ulcer or blisters. Here the authors show, in mouse models of HSV-1 infection, that the pain-perceiving nociceptor Nav1.8+ neurons contribute to regulating both innate and adaptive immune responses against HSV-1, thereby offering a potential target for therapy.
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- 2021
44. Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke
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Almekhlafi, Mohammed, Goyal, Mayank, Dippel, Diederik, Majoie, Charles, Campbell, Bruce, Muir, Keith, Demchuk, Andrew, Bracard, Serge, Guillemin, Francis, Jovin, Tudor, Mitchell, Peter, White, Philip, Hill, Michael, Brown, Scott, Saver, Jeffrey, Berkhemer, Olvert, Fransen, Puck, Beumer, Debbie, Van Den Berg, Lucie, Lingsma, Hester, Yoo, Albert, Schonewille, Wouter, Vos, Jan, Nederkoorn, Paul, Wermer, Marieke, Van Walderveen, Marianne, Staals, Julie, Hofmeijer, Jeannette, Van Oostayen, Jacques, Lycklama À Nijeholt, Geert, Boiten, Jelis, Brouwer, Patrick, Emmer, Bart, De Bruijn, Sebastiaan, Van Dijk, Lukas, Kappelle, L, Lo, Rob, Van Dijk, Ewoud, de Vries, Joost, De Kort, Paul, Van Rooij, Willem, Van Den Berg, Jan, Van Hasselt, Boudewijn, Aerden, Leo, Dallinga, René, Visser, Marieke, Bot, Joseph, Vroomen, Patrick, Eshghi, Omid, Schreuder, Tobien, Heijboer, Roel, Keizer, Koos, Tielbeek, Alexander, Den Hertog, Heleen, Gerrits, Dick, Van Den Berg-Vos, Renske, Karas, Giorgos, Steyerberg, Ewout, Flach, H, Marquering, Henk, Sprengers, Marieke, Jenniskens, Sjoerd, Beenen, Ludo, Van Den Berg, René, Koudstaal, Peter, Van Zwam, Wim, Roos, Yvo, van der Lugt, Aad, Van Oostenbrugge, Robert, Menon, Bijoy, Eesa, Muneer, Rempel, Jeremy, Thornton, John, Roy, Daniel, Willinsky, Robert, Sapkota, Biggya, Dowlatshahi, Dar, Frei, Donald, Kamal, Noreen, Montanera, Walter, Poppe, Alexandre, Ryckborst, Karla, Silver, Frank, Shuaib, Ashfaq, Tampieri, Donatella, Williams, David, Bang, Oh, Baxter, Blaise, Burns, Paul, Choe, Hana, Heo, Ji-Hoe, Holmstedt, Christine, Jankowitz, Brian, KELLY, Michael, Linares, Guillermo, Mandzia, Jennifer, Shankar, Jai, Sohn, Sung-Il, Swartz, Richard, Coutts, Shelagh, Smith, Eric, Morrish, William, Weill, Alain, Subramaniam, Suresh, Mitha, Alim, Wong, John, Lowerison, Mark, Sajobi, Tolulope, Bonafe, Alain, Diener, Hans, Levy, Elad, Pereira, Vitor, Albers, Gregory, Cognard, Christophe, Cohen, David, Hacke, Werner, Jansen, Olav, Mattle, Heinrich, Nogueira, Raul, Siddiqui, Adnan, Yavagal, Dileep, Devlin, Thomas, Lopes, Demetrius, Reddy, Vivek, du Mesnil de Rochemont, Richard, Singer, Oliver, Jahan, Reza, Kleinig, Timothy, Dewey, Helen, Churilov, Leonid, Yassi, Nawaf, Yan, Bernard, Dowling, Richard, Parsons, Mark, Oxley, Thomas, Wu, Teddy, Brooks, Mark, Simpson, Marion, Miteff, Ferdinand, Levi, Christopher, Krause, Martin, Harrington, Timothy, Faulder, Kenneth, Steinfort, Brendan, Priglinger, Miriam, Ang, Timothy, Scroop, Rebecca, Barber, Philip, McGuinness, Ben, Wijeratne, Tissa, Phan, Thanh, Chong, Winston, Chandra, Ronil, Bladin, Christopher, Badve, Monica, Rice, Henry, de Villiers, Laetitia, Ma, Henry, Desmond, Patricia, Donnan, Geoffrey, Davis, Stephen, Chamorro, Angel, Cobo, Erik, De Miquel, María, Molina, Carlos, Rovira, Alex, San Román, Luis, Serena, Joaquín, Abilleira, Sonia, Ribó, Marc, Millán, Mònica, Urra, Xabier, Cardona, Pere, López-Cancio, Elena, Tomasello, Alejandro, Castaño, Carlos, Blasco, Jordi, Aja, Lucía, Dorado, Laura, Quesada, Helena, Rubiera, Marta, Hernandez-Pérez, María, von Kummer, Rüdiger, Gallofré, Miquel, Dávalos, Antoni, Ford, Gary, Messow, Claudia-Martina, Ford, Ian, Murray, Alicia, Clifton, Andrew, Brown, Martin, Madigan, Jeremy, Lenthall, Rob, Robertson, Fergus, Dixit, Anand, Cloud, Geoffrey, Wardlaw, Joanna, Freeman, Janet, Ducrocq, Xavier, Mas, Jean, Soudant, Marc, Oppenheim, Catherine, Moulin, Thierry, University of Calgary, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], University of Melbourne, University of Glasgow, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Newcastle University [Newcastle], Altair Development, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), and University of California-University of California
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[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. OBJECTIVE To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). DATA SOURCES PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020.
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- 2021
45. Major Bleeding of Transjugular Native Kidney Biopsies. A French Nationwide Cohort Study
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Hindricks, Gerhard, Potpara, Tatjana, Dagres, Nikolaos, Arbelo, Elena, Bax, Jeroen, Blomström-Lundqvist, Carina, Boriani, Giuseppe, Castella, Manuel, Dan, Gheorghe-Andrei, Dilaveris, Polychronis, Fauchier, Laurent, Filippatos, Gerasimos, Kalman, Jonathan, La Meir, Mark, Lane, Deirdre, Lebeau, Jean-Pierre, Lettino, Maddalena, Lip, Gregory, Pinto, Fausto, Thomas, G Neil, Valgimigli, Marco, van Gelder, Isabelle, van Putte, Bart, Watkins, Caroline, Kirchhof, Paulus, Kühne, Michael, Aboyans, Victor, Ahlsson, Anders, Balsam, Pawel, Bauersachs, Johann, Benussi, Stefano, Brandes, Axel, Braunschweig, Frieder, Camm, a John, Capodanno, Davide, Casadei, Barbara, Conen, David, Crijns, Harry, Delgado, Victoria, Dobrev, Dobromir, Drexel, Heinz, Eckardt, Lars, Fitzsimons, Donna, Folliguet, Thierry, Gale, Chris, Gorenek, Bulent, Haeusler, Karl Georg, Heidbuchel, Hein, Iung, Bernard, Katus, Hugo, Kotecha, Dipak, Landmesser, Ulf, Leclercq, Christophe, Lewis, Basil, Mascherbauer, Julia, Merino, Jose Luis, Merkely, Béla, Mont, Lluís, Mueller, Christian, Nagy, Klaudia, Oldgren, Jonas, Pavlović, Nikola, Pedretti, Roberto, Petersen, Steffen, Piccini, Jonathan, Popescu, Bogdan, Pürerfellner, Helmut, Richter, Dimitrios, Roffi, Marco, Rubboli, Andrea, Scherr, Daniel, Schnabel, Renate, Simpson, Iain, Shlyakhto, Evgeny, Sinner, Moritz, Steffel, Jan, Sousa-Uva, Miguel, Suwalski, Piotr, Svetlosak, Martin, Touyz, Rhian, Neil Thomas, G, Delassi, Tahar, Sisakian, Hamayak, Chasnoits, Alexandr, Pauw, Michel De, Smajić, Elnur, Shalganov, Tchavdar, Avraamides, Panayiotis, Kautzner, Josef, Gerdes, Christian, Alaziz, Ahmad Abd, Kampus, Priit, Raatikainen, Pekka, Boveda, Serge, Papiashvili, Giorgi, Vassilikos, Vassilios, Csanádi, Zoltán, Arnar, David, Galvin, Joseph, Barsheshet, Alon, Caldarola, Pasquale, Rakisheva, Amina, Bytyçi, Ibadete, Kerimkulova, Alina, Kalejs, Oskars, Njeim, Mario, Puodziukynas, Aras, Groben, Laurent, Sammut, Mark, Grosu, Aurel, Boskovic, Aneta, Moustaghfir, Abdelhamid, Groot, Natasja De, Poposka, Lidija, Anfinsen, Ole-Gunnar, Mitkowski, Przemyslaw, Cavaco, Diogo Magalhães, Siliste, Calin, Mikhaylov, Evgeny, Bertelli, Luca, Kojic, Dejan, Hatala, Robert, Fras, Zlatko, Arribas, Fernando, Juhlin, Tord, Sticherling, Christian, Abid, Leila, Atar, Ilyas, Sychov, Oleg, Bates, Matthew, Zakirov, Nodir, Halimi, Jean-Michel, Gatault, Philippe, Longuet, Hélène, Barbet, Christelle, Goumard, Annabelle, Gueguen, Juliette, Goin, Nicolas, Sautenet, Bénédicte, Herbert, Julien, Bisson, Arnaud, Universität Leipzig [Leipzig], University of Belgrade [Belgrade], Leiden University Medical Center (LUMC), Uppsala University, Università degli Studi di Modena e Reggio Emilia, Colentina University Hospital, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Attikon University Hospital, The Royal Melbourne Hospital, University of Liverpool, San Gerardo Hospital of Monza, Aalborg University [Denmark] (AAU), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA), Hospital de Santa Maria [Lisboa], Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), 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, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
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medicine.medical_specialty ,Framingham Risk Score ,Percutaneous ,business.industry ,medicine.medical_treatment ,kidney biopsy ,Retrospective cohort study ,Odds ratio ,Lower risk ,medicine.disease ,transjugular ,Nephrectomy ,Surgery ,[SHS]Humanities and Social Sciences ,bleeding score ,Hematoma ,percutaneous ,Nephrology ,Clinical Research ,medicine ,epidemiology ,business ,ComputingMilieux_MISCELLANEOUS ,Cohort study - Abstract
Introduction The risk of bleeding associated with transjugular kidney biopsies is unclear, and which patients are the best candidates for this route is unknown. Methods This was a retrospective cohort study comparing proportion of bleeding associated with transjugular versus percutaneous native kidney biopsies in all patients in France in the 2010–2019 period. Major bleeding at day 8 (i.e., blood transfusions, hemorrhage/hematoma, angiographic intervention, nephrectomy) and risk of death at day 30 were assessed, and we used a bleeding risk score initially developed for the percutaneous route. Results Our analysis included 60,331 patients (transjugular route: 5305; percutaneous route: 55,026 patients). The observed proportion of major bleeding varied widely (transjugular vs. percutaneous): 0.4% versus 0.5% for the lowest risk scores (0–4) to 19.1% versus 30.8% for the highest risk scores (≥35). Transjugular was more frequently used than percutaneous route (39% vs. 24%) when the risk score was ≥20 (15,133/60,331; 25% of all patients). Transjugular was associated with a lower risk of major bleeding than percutaneous route in multivariate analyses (odds ratio [OR]: 0.88 [0.78–0.99]), especially for scores ≥20 (OR: 0.83 [0.72–0.96], (i.e., 25% of patients). Major bleeding was associated with an increased risk of death both for transjugular (OR: 1.77 [1.00–3.14]) and percutaneous (OR: 1.80 [1.43–2.28]) routes. Conclusions The transjugular route is independently associated with a lower risk of bleeding than the percutaneous route, especially in high-risk patients identified by a preprocedure risk score ≥20 (i.e., 25% of patients). Major bleeding is associated with an increased risk of death for both routes., Graphical abstract
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- 2021
46. Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
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Cole B. Hirschfeld, Maurizio Dondi, Thomas N.B. Pascual, Mathew Mercuri, Joao Vitola, Ganesan Karthikeyan, Nathan Better, John J. Mahmarian, Salah E. Bouyoucef, Henry Hee-Seung Bom, Vikram Lele, Vincent Peter C. Magboo, Erick Alexánderson, Adel H. Allam, Mouaz H. Al-Mallah, Albert Flotats, Scott Jerome, Philipp A. Kaufmann, Osnat Luxenburg, S. Richard Underwood, Madan M. Rehani, Jenia Vassileva, Diana Paez, Andrew J. Einstein, A.J. Einstein, T.N.B. Pascual, D. Paez, M. Dondi, N. Better, S.E. Bouyoucef, G. Karthikeyan, R. Kashyap, V. Lele, V.P.C. Magboo, J.J. Mahmarian, J.B. Meeks, M. Mercuri, F. Mut, M.M. Rehani, J.V. Vitola, E. Alexanderson, A. Allam, M.H. Al-Mallah, H. Bom, A. Flotats, S. Jerome, P.A. Kaufmann, O. Luxenburg, J. Mahmarian, L.J. Shaw, S.R. Underwood, J. Vitola, W. Amouri, H. Essabbah, S.S. Gassama, K.B. Makhdomi, G.I.E. El Mustapha, N. El Ouchdi, N. Qaïs, N. Soni, W. Vangu, R.M. Abazid, B. Adams, V. Agarwal, M.A. Alfeeli, N. Alnafisi, L. Bernabe, G.G. Bural, T. Chaiwatanarat, J.M. Chandraguptha, G.J. Cheon, I. Cho, A.S. Dogan, M. Eftekhari, A. Frenkel, I. Garty, S. George, P. Geramifar, H. Golan, S. Habib, R. Hussain, H. Im, H.-J. Jeon, T. Kalawat, W.J. Kang, F. Keng, A. Klaipetch, P.G. Kumar, J. Lee, W.W. Lee, I. Lim, C.M.M. Macaisa, G. Malhotra, B.R. Mittal, M.H. Mohammad, P. Mohan, I.D. Mulyanto, D. Nariman, U.N. Nayak, K. Niaz, G. Nikolov, J.M. Obaldo, E. Ozturk, J.M. Park, S. Park, C.D. Patel, H.K. Phuong, A.P. Quinon, T.R. Rajini, Y. Saengsuda, J. Santiago, H.B. Sayman, A.S. Shinto, V. Sivasubramaniyan, M.H. Son, P. Sudhakar, G.M.S. Syed, N. Tamaki, K. Thamnirat, T. Thientunyakit, S. Thongmak, D.N. Velasco, A. Verma, U. Vutrapongwatana, Y. Wang, K.S. Won, Z. Yao, T. Yingsa-nga, R. Yudistiro, K.T. Yue, N. Zafrir, S.C. Adrian, D. Agostini, S. Aguadé, G. Armitage, M. Backlund, M. Backman, M. Baker, M.T. Balducci, C. Bavelaar, M. Berovic, F. Bertagna, R. Beuchel, A. Biggi, G. Bisi, R. Bonini, A. Bradley, L. Brudin, I. Bruno, E. Busnardo, R. Casoni, A. Choudhri, C. Cittanti, R. Clauss, D.C. Costa, M. Costa, K. Dixon, M. Dziuk, N. Egelic, I. Eriksson, G. Fagioli, D.B. de Faria, L. Florimonte, A. Francini, M. French, E. Gallagher, I. Garai, O. Geatti, D. Genovesi, L. Gianolli, A. Gimelli, E. del Giudice, S. Halliwell, M.J. Hansson, C. Harrison, F. Homans, F. Horton, D. Jędrzejuk, J. Jogi, A. Johansen, H. Johansson, M. Kalnina, M. Kaminek, A. Kiss, M. Kobylecka, M. Kostkiewicz, J. Kropp, R. Kullenberg, T. Lahoutte, O. Lang, Y.H. Larsson, M. Lázár, L. Leccisotti, N. Leners, O. Lindner, R.W. Lipp, A. Maenhout, L. Maffioli, C. Marcassa, B. Martins, P. Marzullo, G. Medolago, C.G. Mendiguchía, S. Mirzaei, M. Mori, B. Nardi, S. Nazarenko, K. Nikoletic, R. Oleksa, T. Parviainen, J. Patrina, R. Peace, C. Pirich, H. Piwowarska-Bilska, S. Popa, V. Prakash, V. Pubul, L. Puklavec, S. Rac, M. Ratniece, S.A. Rogan, A. Romeo, M. Rossi, D. Ruiz, N. Sabharwal, B.G. Salobir, A.I. Santos, S. Saranovic, A. Sarkozi, R.P. Schneider, R. Sciagra, S. Scotti, Z. Servini, L.R. Setti, S.-Å. Starck, D. Vajauskas, J. Veselý, A. Vieni, A. Vignati, I.M. Vito, K. Weiss, D. Wild, M. Zdraveska-Kochovska, R.N. Agüro, N. Alvarado, C.M. Barral, M. Beretta, I. Berrocal, J.F. Batista Cuellar, T-M. Cabral Chang, L.O. Cabrera Rodríguez, J. Canessa, G. Castro Mora, A.C. Claudia, G.F. Clavelo, A.F. Cruz Júnior, F.F. Faccio, K.M. Fernández, J.R. Gomez Garibo, U. Gonzalez, P. González E, M.A. Guzzo, J. Jofre, M. Kapitán, G. Kempfer, J.L. Lopez, T. Massardo V, I. Medeiros Colaco, C.T. Mesquita, M. Montecinos, S. Neubauer, L.M. Pabon, A. Puente, L.M. Rochela Vazquez, J.A. Serna Macias, A.G. Silva Pino, F.Z. Tártari Huber, A.P. Tovar, L. Vargas, C. Wiefels, A. Aljizeeri, R.J. Alvarez, D. Barger, W. Beardwood, J. Behrens, L. Brann, D. Brown, H. Carr, K. Churchwell, G.A. Comingore, J. Corbett, M. Costello, F. Cruz, T. Depinet, S. Dorbala, M. Earles, F.P. Esteves, E. Etherton, R.J. Fanning, J. Fornace, L. Franks, H. Gewirtz, K. Gulanchyn, C.-L. Hannah, J. Hays, J. Hendrickson, J. Hester, K. Holmes, A. Johnson, C. Jopek, H. Lewin, J. Lyons, C. Manley, J. Meden, S. Moore, W.H. Moore, V. Murthy, R. Nace, D. Neely, L. Nelson, O. Niedermaier, D. Rice, R. Rigs, K. Schiffer, E. Schockling, T. Schultz, T. Schumacker, B. Sheesley, A. Sheikh, B. Siegel, A.M. Slim, J. Smith, M. Szulc, N. Tanskersley, P. Tilkemeier, G.D. Valdez, R. Vrooman, D. Wawrowicz, D.E. Winchester, A. Alcheikh, B. Allen, E. Atkins, J. Bevan, C. Bonomini, J. Christiansen, L. Clack, E. Craig, H. Dixson, I. Duncan, S. Fredericks, S. Gales, R. Hampson, T. Hanley, K. Hartcher, J. Hassall, B. Kelley, S. Kelly, T. Kidd, T. de Kort, G. Larcos, W. Macdonald, C. McGrath, E. Murdoch, S. O'Malley, M. O'Rourke, M. Pack, R. Pearce, R. Praehofer, S. Ramsay, L. Scarlett, K. Smidt, F. Souvannavong, K. Taubman, G. Taylor, K. Tse, S. Unger, J. Weale, Columbia University Irving Medical Center (CUIMC), New York Presbyterian Hospital, International Atomic Energy Agency [Vienna] (IAEA), McMaster University [Hamilton, Ontario], University of Toronto, All India Institute of Medical Sciences [New Delhi], The Royal Melbourne Hospital, University of Melbourne, Methodist Debakey Heart and Vascular Center [Houston, TX, USA], Houston Methodist Hospital [Houston, TX, USA], Centre Hospitalier Universitaire de Bab-el-Oued, Alger, Algérie., Chonnam National University [Gwangju], Jaslok Hospital & Research Centre, University of the Philippines (UP System), University of Santo Tomas Hospital, Instituto Nacional de Cardiologia Ignacio Chavez, Universidad Nacional Autónoma de México (UNAM), Al-Azhar University [Cairo, Egypt], Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), University of Maryland [Baltimore], University hospital of Zurich [Zurich], The Gertner Institute for Epidemiology and Health Policy Research, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Massachusetts General Hospital [Boston], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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medicine.medical_specialty ,MESH: Radiation Dosage ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,030204 cardiovascular system & hematology ,Single-photon emission computed tomography ,MESH: Tomography, Emission-Computed, Single-Photon ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Myocardial perfusion imaging ,0302 clinical medicine ,MESH: Cross-Sectional Studies ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,MESH: Diagnostic Reference Levels ,Medical imaging ,medicine ,administered activity ,Radiology, Nuclear Medicine and imaging ,Medical physics ,SPECT myocardial perfusion imaging ,Protocol (science) ,MESH: Humans ,medicine.diagnostic_test ,business.industry ,radiation dose reduction ,diagnostic reference level ,MESH: Predictive Value of Tests ,3. Good health ,Predictive value of tests ,Regional studies ,Dose reduction ,Cardiology and Cardiovascular Medicine ,business ,Emission computed tomography ,MESH: Perfusion - Abstract
Objectives This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Background Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. Methods Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. Results The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m–labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. Conclusions This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.
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- 2021
47. Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method
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Ognjen Gajic, Samuel M. Galvagno, Elie Azoulay, Adam M. Deane, Jan Bakker, Massimo Antonelli, Sangeeta Mehta, Pauline K. Park, Yaseen M. Arabi, David Pilcher, Krishnaswamy Sundararajan, Gopi C. Khilnani, Paolo Pelosi, Suveer Singh, Laurent Brochard, Younsuck Koh, Bin Du, Massimiliano Sorbello, Waleed Alhazzani, Jason Phua, Lise Piquilloud, John Victor Peter, Prashant Nasa, Sachin Gupta, Armand Mekontso-Dessap, Manu L N G Malbrain, Sharon Einav, Michael T. McCurdy, Manu Shankar-Hari, Claude Guérin, Yash Javeri, Jean-Baptiste Lascarrou, Samir Jaber, Ashish Khanna, Jordi Mancebo, Pradeep Rangappa, Deven Juneja, Andrés Esteban, Sheila Nainan Myatra, Marcus J. Schultz, Ravindranath Tiruvoipati, Andrew A. Udy, Brendan McGrath, Flávia Ribeiro Machado, Michael Nurok, Tobias Welte, Mervyn Mer, Ravi Jain, Peter Schellongowski, NMC Specialty Hospital, Al Nahda, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Mahatma Gandhi Hospital, Narayana Super Speciality Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, King Saud Bin Abdulaziz University for Health Sciences [Riyadh] (KSAU-HS), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Pontificia Universidad Católica de Chile (UC), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], The Royal Melbourne Hospital, Peking Union Medical College Hospital [Beijing] (PUMCH), Shaare Zedek Medical Center [Jerusalem, Israel], CIBER de Epidemiología y Salud Pública (CIBERESP), Mayo Clinic, University of Maryland School of Medicine, University of Maryland System, 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Ulsan, Centre hospitalier universitaire de Nantes (CHU Nantes), Federal University of Sao Paulo (Unifesp), International Fluid Academy, Vrije Universiteit Brussel [Bruxelles] (VUB), Hospital Universitari Sant Pau, Barcelona, Manchester University NHS Foundation Trust (MFT), Manchester Academic Health Sciences Centre [Manchester, UK], Mount Sinai Health System, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [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 Henri Mondor, University of the Witwatersrand [Johannesburg] (WITS), Cedars-Sinai Medical Center, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Ospedale Policlinico San Martino [Genoa], Università degli studi di Genova = University of Genoa (UniGe), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), National and Kapodistrian University of Athens (NKUA), Monash University [Melbourne], Lausanne University Hospital, Medizinische Universität Wien = Medical University of Vienna, VU University Medical Center [Amsterdam], Mahidol University [Bangkok], University of Oxford [Oxford], Guy's and St Thomas' Hospital [London], King‘s College London, Royal Brompton Hospital, Chelsea and Westminster Hospital, Monash College [Melbourne], German Center for Lung Research - DZL [Munich, Germany], Tata Memorial Centre, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, AII - Infectious diseases, ACS - Diabetes & metabolism, ACS - Microcirculation, and Epidemiology
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medicine.medical_specialty ,ARDS ,COVID-19 acute respiratory distress syndrome ,Consensus ,Delphi Technique ,medicine.medical_treatment ,education ,Delphi method ,Critical Care and Intensive Care Medicine ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Prone ventilation ,03 medical and health sciences ,0302 clinical medicine ,Respiratory Insufficiency/therapy ,COVID-19 high flow nasal oxygen ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,COVID-19 respiratory management ,medicine ,Humans ,COVID-19/complications ,Respiratory Insufficiency/virology ,COVID 19 invasive mechanical ventilation ,COVID-19 ventilatory management ,Respiratory distress syndrome adult ,Intensive care medicine ,Personal protective equipment ,Positive end-expiratory pressure ,11 Medical and Health Sciences ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,business.industry ,Research ,Tracheal intubation ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,COVID-19 ,030208 emergency & critical care medicine ,lcsh:RC86-88.9 ,medicine.disease ,Emergency & Critical Care Medicine ,COVID-19 high fow nasal oxygen ,3. Good health ,030228 respiratory system ,Respiratory failure ,Breathing ,business ,Respiratory Insufficiency - Abstract
Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.
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- 2021
48. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts
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Mark Slee, Guillermo Izquierdo, Per Soelberg Soerensen, Karen Schreiber, Alexandre Prat, Francois Grand'Maison, Maria Trojano, Franco Granella, Pierre Duquette, David Laplaud, Elisabeth Maillart, Henrik Kahr Mathiesen, Bassem Yamout, Cavit Boz, Jean Pelletier, Corinne Pottier, Jette L. Frederiksen, Claudia Christina Pfleger, Tomas Kalincik, Olivier Gout, Daniele Spitaleri, Marc Girard, Marco Onofrj, Jérôme De Seze, Helmut Butzkueven, Emmanuelle Leray, Philippe Cabre, Julie Prevost, Abullatif Al-Khedr, Aude Maurousset, Eric Berger, Sifat Sharmin, Ivania Patry, Pamela A. McCombe, Patrizia Sola, Olga Skibina, Diana Ferraro, Pierre Clavelou, Francesco Patti, Finn Sellebjerg, Niels Koch-Henriksen, Alexis Montcuquet, Recai Turkoglu, Romain Casey, Bart Van Wijmeersch, Hélène Zéphir, Pierre Grammond, Dana Horakova, Davide Maimone, Serkan Ozakbas, Céline Labeyrie, Murat Terzi, Aurélie Ruet, Steve Vucic, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Bruno Stankoff, Mathilde Lefort, Katherine Buzzard, Karolina Hankiewicz, Jean-Philippe Camdessanché, Raed Alroughani, Michael Broksgaard Jensen, Pierre Labauge, Olivier Casez, Peter Vestergaard Rasmussen, Bertrand Bourre, Olivier Heinzlef, Gilles Defer, Gilles Edan, Alessandra Lugaresi, Abir Wahab, Melinda Magyari, Anneke van der Walt, Eva Havrdova, Johanna Balslev Andersen, Chantal Nifle, Stephan Bramow, Marc Debouverie, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Jeannette Lechner-Scott, Eric Thouvenot, Sharmin S., Lefort M., Andersen J.B., Leray E., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand'Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Prevost J., Maimone D., Skibina O., Buzzard K., Van der Walt A., Van Wijmeersch B., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., De Seze J., Maillart E., Zephir H., Labauge P., Defer G., Lebrun-Frenay C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Laplaud D., Koch-Henriksen N., Sellebjerg F.T., Soerensen P.S., Pfleger C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Magyari M., Vukusic S., Butzkueven H., Kalincik T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), Charles University [Prague] (CU), Amiri hospital, Hospital Virgen Macarena, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), University of Catania [Italy], G.F. Ingrassia Hospital, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Neurological Science of Bologna (IRCCS), Ondokuz Mayis University (OMU), American University of Beirut Faculty of Medicine and Medical Center (AUB), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Karadeniz Technical University (KTU), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Queensland [Brisbane], Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Flinders University [Adelaide, Australia], University of Newcastle [Callaghan, Australia] (UoN), Azienda Ospedaleria Universitaria di Modena, Università degli studi di Parma = University of Parma (UNIPR), University Hospital Parma, Monash University [Melbourne], The Alfred Hospital, Hasselt University (UHasselt), University of Debrecen Egyetem [Debrecen], San Giuseppe Moscati Hospital [Avellino, Italie], Westmead Hospital [Sydney], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, Service de neurologie [Amiens], CHU Amiens-Picardie, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en 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), Aarhus University Hospital, Aalborg University [Denmark] (AAU), University Hospital of Northern Sealand, Rigshospitalet [Copenhagen], Copenhagen University Hospital, The Royal Melbourne Hospital, 1140766, National Health and Medical Research Council, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Bologna, University of Bari Aldo Moro (UNIBA), University of Newcastle [Australia] (UoN), University of Parma = Università degli studi di Parma [Parme, Italie], University of Debrecen, 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), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Ondokuz Mayis University, Centre de recherche en neurosciences de Lyon (CRNL), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Internationality ,Subgroup analysis ,Rate ratio ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Natalizumab ,Multiple Sclerosis, Relapsing-Remitting ,030225 pediatrics ,Internal medicine ,Secondary Prevention ,Medicine ,Humans ,Immunologic Factors ,Pharmacology (medical) ,Longitudinal Studies ,Registries ,10. No inequality ,Expanded Disability Status Scale ,business.industry ,Proportional hazards model ,Fingolimod Hydrochloride ,Multiple sclerosis ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Middle Aged ,medicine.disease ,Fingolimod ,3. Good health ,multiple sclerosis, sex, age, natalizumab, fingolimod, big data ,Psychiatry and Mental health ,Cohort ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Immunosuppressive Agents ,medicine.drug ,Follow-Up Studies - Abstract
Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed withweighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤38 years (0.64; 0.54–0.76); in those withdisease duration ≤7 years (0.63; 0.53–0.76); in those with EDSS score 38 years (1.34; 1.04–1.73); those with disease duration >7 years (1.33; 1.01–1.74); those with EDSS score
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- 2021
49. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN) : a phase 1/2 study
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Ming Yin, Edward Y. Zhu, Justin Taylor, Michael Wang, Anthony R. Mato, Matthew S. Davids, Nora Ku, Lindsey E. Roeker, Ian W. Flinn, Jennifer A. Woyach, Johan Wallin, Nicole Lamanna, Timothy S. Fenske, Donald E. Tsai, Steven Le Gouill, Suchitra Sundaram, David J. Lewis, John M. Pagel, Toby A. Eyre, Catherine C. Coombs, Stephen J. Schuster, Kevin Ebata, Xuan Ni Tan, Manish R. Patel, Jonathon B. Cohen, Narasimha Marella, Katharine L Lewis, Chan Yoon Cheah, Omar Abdel-Wahab, Bita Fakhri, Binoj Nair, Bryone J. Kuss, M. Lia Palomba, Constantine S. Tam, Alvaro J. Alencar, Wojciech Jurczak, Nirav N. Shah, James N. Gerson, Jennifer R. Brown, Paolo Ghia, Ewa Lech-Marańda, Minal A Barve, Jessica A. Chen, William G. Wierda, Memorial Sloane Kettering Cancer Center [New York], Medical College of Wisconsin [Milwaukee] (MCW), Maria Sklodowska-Curie National Research Institute of Oncology [Krakow, Poland], The University of Western Australia (UWA), Swedish Cancer Institute [Seattle, WA, USA] (SCI), Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Oxford University Hospitals NHS Trust, University of Oxford, Columbia University [New York], Sarah Cannon Research Institute [Sarasota, FL, USA] (SCRI), University of Miami Leonard M. Miller School of Medicine (UMMSM), Institute of Hematology and Transfusion Medicine[Warsaw, Poland] (IHTM), MD Anderson Cancer Center [Houston, TX, USA] (MDACC), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Pennsylvania, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospitals Plymouth NHS Trust [Plymouth, UK] (UHP), Roswell Park Comprehensive Cancer Center [Buffalo, NY, USA] (RP3C), Emory University [Atlanta, GA], Sarah Cannon Research Institute [Nashville, Tennessee], University of Melbourne, The Royal Melbourne Hospital, Mary Crowley Cancer Research Center [Dallas, TX, USA] (M2CRC), Flinders University Medical Centre [Bedford Park, SA, Australia] (FUMC), Memorial Sloan Kettering Cancer Center [New York, NY, USA] (MSK2C), Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Medical College of Wisconsin [Milwaukee, WI, USA] (MCW), Loxo Oncology at Lilly [Stamford, CT, USA] (LO), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Bernardo, Elizabeth, University of California [San Francisco] (UCSF), University of California, University of Oxford [Oxford], University of Pennsylvania [Philadelphia], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Mato, A. R., Shah, N. N., Jurczak, W., Cheah, C. Y., Pagel, J. M., Woyach, J. A., Fakhri, B., Eyre, T. A., Lamanna, N., Patel, M. R., Alencar, A., Lech-Maranda, E., Wierda, W. G., Coombs, C. C., Gerson, J. N., Ghia, P., Le Gouill, S., Lewis, D. J., Sundaram, S., Cohen, J. B., Flinn, I. W., Tam, C. S., Barve, M. A., Kuss, B., Taylor, J., Abdel-Wahab, O., Schuster, S. J., Palomba, M. L., Lewis, K. L., Roeker, L. E., Davids, M. S., Tan, X. N., Fenske, T. S., Wallin, J., Tsai, D. E., Ku, N. C., Zhu, E., Chen, J., Yin, M., Nair, B., Ebata, K., Marella, N., Brown, J. R., and Wang, M.
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Adult ,Male ,medicine.medical_specialty ,Lymphoma, B-Cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Lymphoma, Mantle-Cell ,030204 cardiovascular system & hematology ,Neutropenia ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Clinical endpoint ,Bruton's tyrosine kinase ,Humans ,030212 general & internal medicine ,Adverse effect ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Hematology ,biology ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Lymphoma ,Pyrimidines ,Treatment Outcome ,biology.protein ,Pyrazoles ,Mantle cell lymphoma ,Female ,business - Abstract
International audience; Background: Covalent Bruton's tyrosine kinase (BTK) inhibitors are efficacious in multiple B-cell malignancies, but patients discontinue these agents due to resistance and intolerance. We evaluated the safety and efficacy of pirtobrutinib (working name; formerly known as LOXO-305), a highly selective, reversible BTK inhibitor, in these patients.Methods: Patients with previously treated B-cell malignancies were enrolled in a first-in-human, multicentre, open-label, phase 1/2 trial of the BTK inhibitor pirtobrutinib. The primary endpoint was the maximum tolerated dose (phase 1) and overall response rate (ORR; phase 2). This trial is registered with ClinicalTrials.gov, NCT03740529.Findings: 323 patients were treated with pirtobrutinib across seven dose levels (25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg once per day) with linear dose-proportional exposures. No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. The recommended phase 2 dose was 200 mg daily. Adverse events in at least 10% of 323 patients were fatigue (65 [20%]), diarrhoea (55 [17%]), and contusion (42 [13%]). The most common adverse event of grade 3 or higher was neutropenia (32 [10%]). There was no correlation between pirtobrutinib exposure and the frequency of grade 3 treatment-related adverse events. Grade 3 atrial fibrillation or flutter was not observed, and grade 3 haemorrhage was observed in one patient in the setting of mechanical trauma. Five (1%) patients discontinued treatment due to a treatment-related adverse event. In 121 efficacy evaluable patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) treated with a previous covalent BTK inhibitor (median previous lines of treatment 4), the ORR with pirtobrutinib was 62% (95% CI 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (53 [67%] of 79), covalent BTK inhibitor intolerance (22 [52%] of 42), BTK C481-mutant (17 [71%] of 24) and BTK wild-type (43 [66%] of 65) disease. In 52 efficacy evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but eight remain progression-free to date.Interpretation: Pirtobrutinib was safe and active in multiple B-cell malignancies, including patients previously treated with covalent BTK inhibitors. Pirtobrutinib might address a growing unmet need for alternative therapies for these patients.Funding: Loxo Oncology.
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- 2021
50. Response to Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma and Atopic Phenotypes
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Jo A Douglass, Charlene M. Prazma, Steven W. Yancey, Frank C. Albers, Marco Idzko, Arnaud Bourdin, Stephen Mallett, GlaxoSmithKline [Research Triangle Park] (GSK ), Medizinische Universität Wien = Medical University of Vienna, University Hospital Freiburg, The Royal Melbourne Hospital, University of Melbourne, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), GlaxoSmithKline (GSK), and Herrada, Anthony
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,asthma treatments ,Eosinophilic asthma ,Placebo ,Gastroenterology ,Atopy ,Internal medicine ,Post-hoc analysis ,medicine ,Journal of Asthma and Allergy ,Immunology and Allergy ,biologics ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,Asthma ,Original Research ,House dust mite ,biology ,business.industry ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,asthma ,medicine.disease ,biology.organism_classification ,body regions ,allergens and epitopes ,Asthma Control Questionnaire ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,eosinophils ,[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy ,business ,Mepolizumab ,[SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology ,medicine.drug - Abstract
Purpose Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions. Patients and Methods This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (17.5 kU/L]), and by house dust mite (HDM) sensitivity. Results Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥300 cells/µL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of, Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/l92s5nzD3OI
- Published
- 2021
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