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6,478 results on '"Guy's and St Thomas NHS Foundation Trust [London]"'

1. Therapy Strategies After LAA Occluder Device Embolization (LAAODE)

Author: Kerstin Piayda, CardioVascular Center Frankfurt, Frankfurt, Germany, Kolja Sievert, CardioVascular Center Frankfurt, Frankfurt, Germany, Roberto Galea, Universitätsspital Bern, Bern, Switzerland, Moniek Maarse, St. Antonius Ziekenhuis, Nieuwegein, Netherlands, Sheba Medical Center, Andrey Osadchiy, City Hospital #40, St. Petersburg, Russia, Andrey Kalemberg, National Research Center, Moscow, Russia, Jung-Sun Kim, Yonsei University Hospital, Seoul, South Korea, Kasper Korsholm, Aarhus University Hospital, Aarhus, Denmark, Sajjad A Sabir, Cooper University Hospital, NJ, USA, Ashish Pershad, Banner Health, Phoenix, Arizona, USA, Markus Sandri, Herzzentrum Leipzig, Leipzig, Germany, Jens-Erik Nielsen-Kudsk, University Hospital Aarhus, Aarhus, Denmark, George Mark, The Heart House/Cooper University Camden, NJ, USA, Dhiraj Gupta, Liverpool Heart and Chest Hospital, Liverpool, UK, Pradhum Ram, Emory University, USA, Ole de Backer, Rigshospitalet Copenhagen, Denmark, Norbert Klein, Klinikum St. Georg, Leipzig, Germany, Josep Rodes, Laval Hospital, Quebec, Canada, Shazia Afzal, Heinrich-Heine University, University Hospital, Duesseldorf, Xavier Millán Alvarez, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, James E. Harvey, WellSpan Health, York, PA, USA, Wern Yew Ding, University of Liverpool, Liverpool, UK, Adel Aminian, Centre hospitalier universitaire de Charleroi, Brussels, Belgium, Pamela Moceri, Hopital Pasteur 1, Nice, France, Ibrahim Akin, Universitätsmedizin Mannheim, Germany, Jacques Mansourati, Hôpital de la Cavale Blanche, Brest, France, Eloi Marijon, Hôpital Européen Georges-Pompidou HEGP, Paris, France, Ignacio Amat Santos, University Clinical Hospital of Valladolid, Valladolid, Spain, Hana Vaknin Assa, Beilinson Hospital, Israel, Thomas Robert Schmidt, Herzzentrum Dresden GmbH Universitätsklinik, Dresden, Germany, Ran Kornowski, Rabin Medical Center, Petah Tiqwa, Israel, Giacomo Boccuzzi, Ospedale san Giovanni Bosco, Torino, Italy, Christopher R. Ellis, Vanderbilt University, Nashville, TN, USA, Henning Ebelt, Katholisches Krankenhaus St. Nepomuk, Erfurt, Germany, Brian Clapp, Guy's and St Thomas' NHS Foundation Trust, London, UK, Sonja Lehmann, Hôpital Fribourgeois, Freiburg, Swizerland, Oh-Hyun Lee, Yonsai University Hospital, Yongin, Korea, Wendy Schell, Cooper University Hospital, NJ, USA, Domenico della Rocca, St David's Medical Center, Austin, Texas, USA, Pablo Pinon Esteban, Hospital Universitario A Coruña, Spain, Jose Gabriel Galache Osuna, Miguel Servet University Hospital, Zaragoza, Spain, Enio Guerios, Hospital Pilar, Curitiba, Brazil, Nicolas Amabile, Institut Mutualiste Montsouris, Paris, France, Ignacio Cruz Gonzalez, University Hospital of Salamanca, Castillay Leon, Spain, Weita Chen, Taipei Municipal Wanfang Hospital, Taipei, Taiwan, Sandeep Kumar Goyal, Piedmont Heart Institute Buckhead, Atlanta, GA, USA, Francesco Gianni, Maria Cecilia Hospital, Cotignola, Italy, Máximo Rivero Ayerza, Ziekenhuis Oost Limburg, Genk, Belgium, Carsten Skurk, Charité, Universitätsmedizin Berlin, Berlin, Germany, Martin Langel, Klinikum St. Georg, Leipzig, Germany, Livia Gheorghe, Hospital de la Santa Creu I Santa Pau, Barcelona, Spain, Lino Santos, Centro Hospitalar Vila Nova de Gaia, Vila Nova de Gaia, Portugal, Mark Spence, Royal Victoria Hospital, Belfast Trust, Belfast, UK, Luis Nombela-Franco, Hospital Clínico San Carlos, Madrid, Spain, Francesco Nappi, Centre Cardiologique du Nord de Saint-Denis, Paris, France, Matteo Montorfano, Ospedale San Raffaele, Segrate, Milan, Italy, Juan Fernández-Armenta, Hospital Universitario Puerta del Mar, Cádiz, Spain, Michael Kühne, Universitätsspital Basel, Basel, Swizerland, Jesper van der Pals, Lund University Hospital, Lund, Sweden., Can Yücel Karabay, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey, Marco Ancona, San Raffaele Scientific Institute, Milan, Italy, Ghassan Moubarak, Clinique Ambroise Paré, Neuilly-sur-Seine, France, Tom De Potter, OLV Hospital, Aalst, Belgium, Mathieu Lempereur, CHU de Liège, Belgium, Joelle Kefer, Cliniques universitaires Saint-Luc, Bruxelles, Belgium, Evgeny Merkulov, Scientific Research Center, Moscow, Russia, Liesbeth Rosseel, ASZ Aalst, Belgium, Antti Saraste, Heart Center, Turku University Hospital, Turku, Finland, Ahmet Güner, Mehmet Akif Ersoy Hospital, Turkey, Achille Gaspardone, San Eugenio Hospital ASL Roma, Italy, and Prof. Dr. Horst Sievert, Principle Investigator
Published: 2022

2. Symptomatic benefit of momelotinib in patients with myelofibrosis: Results from the <scp>SIMPLIFY</scp> phase <scp>III</scp> studies

Author: Ruben A. Mesa, Stacie Hudgens, Lysbeth Floden, Claire N. Harrison, Jeanne Palmer, Vikas Gupta, Donal P. McLornan, Mary F. McMullin, Jean‐Jaques Kiladjian, Lynda Foltz, Uwe Platzbecker, M. Laura Fox, Adam J. Mead, David M. Ross, Stephen T. Oh, Andrew Perkins, Michael F. Leahy, Samineh Deheshi, Rafe Donahue, Barbara J. Klencke, Srdan Verstovsek, Institut Català de la Salut, [Mesa RA] Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA. [Hudgens S, Floden L] Clinical Outcomes Solutions, Tucson, Arizona, USA. [Harrison CN] Guy's and St. Thomas' NHS Foundation Trust, London, UK. [Palmer J] Mayo Clinic, Phoenix, Arizona, USA. [Gupta V] University Health Network, University of Toronto, Toronto, Ontario, Canada. [Fox ML] Servei d’Hematologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Otros calificadores::/uso terapéutico [Otros calificadores], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], myelofibrosis, momelotinib, Other subheadings::Other subheadings::/drug therapy [Other subheadings], JAK inhibitor, Oncology, Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Primary Myelofibrosis [DISEASES], patient-reported outcomes, Mielofibrosi - Tractament, symptoms, enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::mielofibrosis primaria [ENFERMEDADES], Radiology, Nuclear Medicine and imaging, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors::Janus Kinase Inhibitors [CHEMICALS AND DRUGS], Other subheadings::/therapeutic use [Other subheadings], Proteïnes quinases - Inhibidors - Ús terapèutic, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas::inhibidores de las cinasas Janus [COMPUESTOS QUÍMICOS Y DROGAS]
Abstract: Momelotinib; Myelofibrosis; Patient-reported outcomes Momelotinib; Mielofibrosi; Resultats informats pel pacient Momelotinib; Mielofibrosis; Resultados informados por el paciente Background Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. Methods Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. Results Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of
Published: 2023

3. Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors

Author: Jason J. Luke, Marwan Fakih, Charles Schneider, E. Gabriela Chiorean, Johanna Bendell, Rebecca Kristeleit, Razelle Kurzrock, Sarah P. Blagden, Irene Brana, Laura W. Goff, Kevin O’Hayer, Ryan Geschwindt, Michael Smith, Feng Zhou, Aung Naing, Institut Català de la Salut, [Luke JJ] UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [Fakih M] City of Hope Comprehensive Cancer Center, Duarte, CA, USA. [Schneider C] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. [Chiorean EG] University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Bendell J] Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA. [Kristeleit R] Guy’s and St. Thomas’ NHS Foundation Trust, London, UK. [Kurzrock R] University of California San Diego School of Medicine, La Jolla, CA, USA. [Blagden SP] Early Phase Clinical Trials Unit, University of Oxford, Oxford, England, UK. [Brana I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Cancer Research, Oncology, Otros calificadores::/uso terapéutico [Otros calificadores], Càncer - Tractament, Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::/therapeutic use [Other subheadings], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Càncer - Aspectes genètics
Abstract: Background Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors. Methods ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary endpoints were safety/tolerability (Phase I), maximum tolerated dose (MTD) or pharmacologically active dose (PAD; Phase I), and investigator-assessed objective response rate (ORR; Phase II). Results In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) was treatment-related. Conclusions Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy.
Published: 2023

4. Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients

Author: Elena Levtchenko, Aude Servais, Sally A Hulton, Gema Ariceta, Francesco Emma, David S Game, Karin Lange, Risto Lapatto, Hong Liang, Rebecca Sberro-Soussan, Rezan Topaloglu, Anibh M Das, Nicholas J A Webb, Christoph Wanner, Institut Català de la Salut, [Levtchenko E] Department of Pediatrics, University Hospitals Leuven Campus Gasthuisberg, KU Leuven, Leuven, Belgium. [Servais A] Nephrology and Transplantation Department, Hôpital Necker Enfants Malades APHP, Paris, France. [Hulton SA] Department of Nephrology, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Emma F] Division of Nephrology and Dialysis, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy. [Game DS] Department of Renal Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cistinosi - Tractament, administración de los servicios de salud::gestión de la atención al paciente::tratamiento de las enfermedades [ATENCIÓN DE SALUD], Qüestionaris, ILLNESS, Behavior and Behavior Mechanisms::Psychology, Social::Group Processes::Consensus [PSYCHIATRY AND PSYCHOLOGY], conducta y mecanismos de la conducta::psicología social::procesos de grupo::consenso [PSIQUIATRÍA Y PSICOLOGÍA], multidisciplinary care, NEPHROPATHIC CYSTINOSIS, consensus statements, cysteamine, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::enfermedades por almacenamiento lisosómico::cistinosis [ENFERMEDADES], Health Services Administration::Patient Care Management::Disease Management [HEALTH CARE], OUTCOMES, Transplantation, Science & Technology, MUTATIONS, Presa de decisions, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Lysosomal Storage Diseases::Cystinosis [DISEASES], rare diseases, NATURAL-HISTORY, Urology & Nephrology, clinical recommendations, cystinosis, CRYSTALS, disease management, Nephrology, adult and adolescent, SUCCESSFUL PREGNANCY, Life Sciences & Biomedicine, checklist
Abstract: Clinical recommendations; Cystinosis; Multidisciplinary care Recomendaciones clínicas; Cistinosis; Atención multidisciplinaria Recomanacions clíniques; Cistinosi; Atenció multidisciplinària Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10–20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis. The programme was led by a Steering Committee (SC) of six experts in the management of patients with cystinosis, who identified a list of 15 key questions reflecting the multi-organ effects of cystinosis. An Extended Faculty (EF) of eight additional specialists was invited to answer the questions via an online digital platform using a quasi-Delphi approach. The consolidated answers were summarized into recommendations. Where evidence was lacking, recommendations were developed using collective expert consensus. The EF was asked to agree/disagree with the clinical recommendations. The expert-agreed clinical recommendations provide guidance that considers both renal and extra-renal systems. The topics covered are advice on fertility and family planning, consideration of the nervous, muscular, ophthalmic, cardio-respiratory, endocrine, dermatological and gastrointestinal systems, as well as guidance on dental care, diet, lifestyle, and improving quality of life and psychological well-being. In summary, this work outlines recommendations and a checklist for clinicians with a vision for improving and standardizing the multidisciplinary care for patients with cystinosis. The programme was supported by Chiesi Farmaceutici Spa. Chiesi was not involved in the content or outcomes of the programme which were solely determined by the SC and extended faculty experts.
Published: 2022

5. Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study

Author: Lee, S. I., Azcoaga-Lorenzo, A., Agrawal, U., Kennedy, J. I., Fagbamigbe, A. F., Hope, H., Subramanian, A., Anand, A., Taylor, B., Nelson-Piercy, C., Damase-Michel, C., Yau, C., Crowe, F., Santorelli, G., Eastwood, K-A., Vowles, Z., Loane, M., Moss, N., Brocklehurst, P., Plachcinski, R., Thangaratinam, S., Black, M., O'Reilly, D., Abel, K. M., Brophy, S., Nirantharakumar, K., McCowan, C., MuM-PreDiCT Group, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of Birmingham [Birmingham], University of St Andrews [Scotland], Swansea University, University of Ibadan, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bradford Institute for Health Research [Bradford, UK], Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), Queen's University [Belfast] (QUB), University Hospitals Bristol, University of Ulster, Patient and Public Representative [London, UK] (P&PR), Birmingham Women's and Children's NHS Foundation Trust, University of Aberdeen, Manchester University NHS Foundation Trust (MFT), MuM-PreDiCT Group, and Malbec, Odile
Subjects: Adult, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Maternity, Datasets as Topic, E-DAS, RT, Young Adult, SDG 3 - Good Health and Well-being, RA0421, Pregnancy, RA0421 Public health. Hygiene. Preventive Medicine, Prevalence, Humans, MCC, Multiple long-term conditions, United Kingdom/epidemiology, Obstetrics and Gynecology, Multimorbidity, Gynecology and obstetrics, Middle Aged, United Kingdom, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Multiple chronic conditions, RG Gynecology and obstetrics, RG1-991, Female, Pregnant Women, RG, Routinely Collected Health Data
Abstract: Background Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). Study design Pregnant women aged 15–49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. Results The prevalence of multimorbidity was 44.2% (95% CI 43.7–44.7%), 46.2% (45.6–46.8%) and 19.8% (18.8–20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8–24.6%], 23.5% [23.0–24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8–31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04–3.17] 45–49 years vs 15–19 years), multigravid (1.68 [1.50–1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44–1.76], body mass index 30+ vs body mass index 18.5–24.9) and smoked preconception (1.61 [1.46–1.77) vs non-smoker). Conclusion Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children.
Published: 2022

6. Novel DNM1L variants impair mitochondrial dynamics through divergent mechanisms

Author: Kelsey A Nolden, John M Egner, Jack J Collier, Oliver M Russell, Charlotte L Alston, Megan C Harwig, Michael E Widlansky, Souphatta Sasorith, Inês A Barbosa, Andrew GL Douglas, Julia Baptista, Mark Walker, Deirdre E Donnelly, Andrew A Morris, Hui Jeen Tan, Manju A Kurian, Kathleen Gorman, Santosh Mordekar, Charu Deshpande, Rajib Samanta, Robert McFarland, R Blake Hill, Robert W Taylor, Monika Oláhová, Medical College of Wisconsin [Milwaukee] (MCW), Newcastle University [Newcastle], McGill University = Université McGill [Montréal, Canada], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), King‘s College London, University Hospital Southampton NHS Foundation Trust, University of Southampton, Plymouth University, Belfast City Hospital, Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester], Central Manchester University Hospitals [Manchester, U.K.], University College of London [London] (UCL), Children's Health Ireland [Crumlin, Dublin, Ireland] (CHI), University College Dublin [Dublin] (UCD), Sheffield Children's NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust [London, UK], University Hospitals Leicester, and MORNET, Dominique
Subjects: [SDV] Life Sciences [q-bio], Ecology, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous)
Abstract: Imbalances in mitochondrial and peroxisomal dynamics are associated with a spectrum of human neurological disorders. Mitochondrial and peroxisomal fission both involve dynamin-related protein 1 (DRP1) oligomerisation and membrane constriction, although the precise biophysical mechanisms by which distinct DRP1 variants affect the assembly and activity of different DRP1 domains remains largely unexplored. We analysed four unreported de novo heterozygous variants in the dynamin-1-like geneDNM1L, affecting different highly conserved DRP1 domains, leading to developmental delay, seizures, hypotonia, and/or rare cardiac complications in infancy. Single-nucleotide DRP1 stalk domain variants were found to correlate with more severe clinical phenotypes, with in vitro recombinant human DRP1 mutants demonstrating greater impairments in protein oligomerisation, DRP1-peroxisomal recruitment, and both mitochondrial and peroxisomal hyperfusion compared to GTPase or GTPase-effector domain variants. Importantly, we identified a novel mechanism of pathogenesis, where a p.Arg710Gly variant uncouples DRP1 assembly from assembly-stimulated GTP hydrolysis, providing mechanistic insight into how assembly-state information is transmitted to the GTPase domain. Together, these data reveal that discrete, pathologicalDNM1Lvariants impair mitochondrial network maintenance by divergent mechanisms.
Published: 2022

7. Biallelic variants in TAMM41 are associated with low muscle cardiolipin levels, leading to neonatal mitochondrial disease

Author: Kyle Thompson, Lucas Bianchi, Francesca Rastelli, Florence Piron-Prunier, Sophie Ayciriex, Claude Besmond, Laurence Hubert, Magalie Barth, Inês A. Barbosa, Charu Deshpande, Manali Chitre, Sarju G. Mehta, Eric J.M. Wever, Pascale Marcorelles, Sandra Donkervoort, Dimah Saade, Carsten G. Bönnemann, Katherine R. Chao, Chunyu Cai, Susan T. Iannaccone, Andrew F. Dean, Robert McFarland, Frédéric M. Vaz, Agnès Delahodde, Robert W. Taylor, Agnès Rötig, Newcastle University [Newcastle], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), King‘s College London, Guy's and St Thomas NHS Foundation Trust [London], Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), University of Amsterdam [Amsterdam] (UvA), Amsterdam Public Health Research Institute [The Netherlands], Amsterdam UMC - Amsterdam University Medical Center, Laboratoire sur les interactions Epithéliums Neurones (LIEN), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Texas Southwestern Medical Center [Dallas], Newcastle Upon Tyne Hospitals NHS Foundation Trust, This study was financially supported by the Agence Nationale de la Recherche through the Investissements d'Avenir program ANR-10-IAHU-01 (A.R., L.B., C.B., and L.H.), the E-Rare project GENOMIT (01GM1207, A.R. and L.B.), the French National Agency for Research (ANR-16-CE16-0025-04, A.D. and F.P.-P.), and the 'Association Francaise contre les Myopathies' (AFM -MITOSCREEN, project no. 17122, A.D. and F.P.-P.). We acknowledge the use of bioresources of the Necker Imagine DNA biobank (BB-033-00065). R.M. and R.W.T. are supported by the Wellcome Trust Centre for Mitochondrial Research (203105/Z/16/Z), the Medical Research Council (MRC) International Center for Genomic Medicine in Neuromuscular Disease (MR/S005021/1), the Mitochondrial Disease Patient Cohort (UK) (G0800674), the UK NIHR Biomedical Research Center for Aging and Age-Related Disease Award to the Newcastle upon Tyne Foundation Hospitals NHS Trust, the Lily Foundation, and the UK NHS Specialist Commissioners, which funds the 'Rare Mitochondrial Disorders of Adults and Children' Diagnostic Service in Newcastle upon Tyne. R.W.T. also receives financial support from the Pathology Society. K.T. and I.A.B. were supported by the Lily Foundation. C.G.B. is supported by intramural funds from the NIH National Institute of Neurological Disorders and Stroke. Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute grant UM1 HG008900 to Daniel MacArthur and Heidi Rehm., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Bussy, Agnès, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, and APH - Methodology
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, WES/WGS, OXPHOS defect, mitochondria, mitochondrial disease, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [CHIM] Chemical Sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Medicine, [CHIM]Chemical Sciences, mitochondrial phospholipid, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cardiolipin, Genetics (clinical)
Abstract: International audience; Mitochondrial disorders are clinically and genetically heterogeneous, with variants in mitochondrial or nuclear genes leading to varied clinical phenotypes. TAMM41 encodes a mitochondrial protein with cytidine diphosphate-diacylglycerol synthase activity: an essential early step in the biosynthesis of phosphatidylglycerol and cardiolipin. Cardiolipin is a mitochondria-specific phospholipid that is important for many mitochondrial processes. We report three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis. Whole exome and genome sequencing identified compound heterozygous variants in TAMM41 in each proband. Western blot analysis in fibroblasts showed a mild oxidative phosphorylation (OXPHOS) defect in only one of the three affected individuals. In skeletal muscle samples, however, there was severe loss of subunits of complexes I-IV and a decrease in fully assembled OXPHOS complexes I-V in two subjects as well as decreased TAMM41 protein levels. Similar to the tissue-specific observations on OXPHOS, cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. To assess the functional impact of the TAMM41 missense variants, the equivalent mutations were modeled in yeast. All three mutants failed to rescue the growth defect of the Δtam41 strains on non-fermentable (respiratory) medium compared with wild-type TAM41, confirming the pathogenicity of the variants. We establish that TAMM41 is an additional gene involved in mitochondrial phospholipid biosynthesis and modification and that its deficiency results in a mitochondrial disorder, though unlike families with pathogenic AGK (Sengers syndrome) and TAFAZZIN (Barth syndrome) variants, there was no evidence of cardiomyopathy.
Published: 2022

8. The Young Geneticists Network and the ESHG-Young committee, a forward-looking international community

Author: Riccardi, Florence, Marcinkute, Ruta, Azevedo Soares, Celia, Calapod, Patricia Stefana, Cerqueira, Juliana Miranda, Avram, Elena, Ding, Can, 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), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Guy's and St Thomas NHS Foundation Trust [London], Universidade do Porto = University of Porto, University of Tampere [Finland], and University Medical Center of the Johannes Gutenberg-University Mainz
Subjects: Viewpoint, [SDV]Life Sciences [q-bio], Genetics, Medical, Physicians, Genetics, Humans, ComputingMilieux_MISCELLANEOUS, Genetics (clinical)
Abstract: International audience; No abstract available
Published: 2022

9. Development and Optimization of a Machine- Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort

Author: Mahmoud Aldraimli, Sarah Osman, Diana Grishchuck, Samuel Ingram, Robert Lyon, Anil Mistry, Jorge Oliveira, Robert Samuel, Leila E.A. Shelley, Daniele Soria, Miriam V. Dwek, Miguel E. Aguado-Barrera, David Azria, Jenny Chang-Claude, Alison Dunning, Alexandra Giraldo, Sheryl Green, Sara Gutiérrez-Enríquez, Carsten Herskind, Hans van Hulle, Maarten Lambrecht, Laura Lozza, Tiziana Rancati, Victoria Reyes, Barry S. Rosenstein, Dirk de Ruysscher, Maria C. de Santis, Petra Seibold, Elena Sperk, R. Paul Symonds, Hilary Stobart, Begoña Taboada-Valadares, Christopher J. Talbot, Vincent J.L. Vakaet, Ana Vega, Liv Veldeman, Marlon R. Veldwijk, Adam Webb, Caroline Weltens, Catharine M. West, Thierry J. Chaussalet, Tim Rattay, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Institut Català de la Salut, [Aldraimli M] Health Innovation Ecosystem, University of Westminster, London, United Kingdom. [Osman S] Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom. [Grishchuck D] Imperial College Healthcare NHS Trust, London, United Kingdom. [Ingram S] Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom. [Lyon R] Department of Computer Science, Edge Hill University, Ormskirk, Lancashire, United Kingdom. [Mistry A] Guy's and St. Thomas’ NHS Foundation Trust, London, United Kingdom. [Giraldo A, Reyes V] Servei d’Oncologia Radioteràpica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Gutiérrez-Enríquez S] Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], BIOMARKERS, R895-920, Otros calificadores::Otros calificadores::/radioterapia [Otros calificadores], Nuclear Medicine and imaging, NORMAL TISSUE, Other subheadings::/radiation effects [Other subheadings], Medical physics. Medical radiology. Nuclear medicine, Mama - Càncer - Radioteràpia, SDG 3 - Good Health and Well-being, RISK-FACTOR, Aprenentatge automàtic, Medicine and Health Sciences, Radiology, Nuclear Medicine and imaging, QA, Otros calificadores::/efectos de la radiación [Otros calificadores], RC254-282, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Science & Technology, Other subheadings::Other subheadings::/radiotherapy [Other subheadings], Radiology, Nuclear Medicine & Medical Imaging, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ACUTE SKIN TOXICITY, Oncology, integumento común::piel [ANATOMÍA], Radiology, Pell - Efecte de la radiació, Life Sciences & Biomedicine, Integumentary System::Skin [ANATOMY], RADIOTHERAPY
Abstract: Breast Radiation Therapy; Machine-Learning Prediction; Acute Desquamation Raditeràpia de mama; Predicció d'aprenentatge automàtic; Descamació aguda Radioterapia de mama; Predicción de aprendizaje automático; Descamación aguda Purpose Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the “hero” model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan.
Published: 2022

10. European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part II:psychological interventions

Author: Andreas Hartmann, Sharon Zimmerman-Brenner, Per E. Andrén, Sally Robinson, Kirsten R. Müller-Vahl, Ewgeni Jakubovski, Christos Ganos, Veit Roessner, Katrin Woitecki, Nanette Mol Debes, Zsanett Tarnok, Natalia Szejko, Tara Murphy, Jolande van de Griendt, Paula Viefhaus, Danielle C. Cath, Cara Verdellen, Karolinska Institutet [Stockholm], Hannover Medical School [Hannover] (MHH), Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], University Hospital of Cologne [Cologne], Vadaskert Child and Adolescent Psychiatric Hospital, Baruch Ivcher School of Psychology, Guy's and St Thomas NHS Foundation Trust [London], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical University of Warsaw - Poland, Yale University School of Medicine, University of Groningen [Groningen], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Tic disorder, Exposure and response prevention, Tics, Tic disorders, RESPONSE PREVENTION, medicine.medical_treatment, Habit reversal training, Psychological intervention, CHILDREN, Review, PsycINFO, Psychosocial Intervention, Tourette syndrome, HABIT-REVERSAL, HABITUATION, 03 medical and health sciences, 0302 clinical medicine, mental disorders, ADOLESCENTS, Developmental and Educational Psychology, Child and adolescent psychiatry, Psychoeducation, Treatment guidelines, Humans, Medicine, EXPOSURE, Psychiatry, COGNITIVE-BEHAVIORAL THERAPY, PILOT TRIAL, Comprehensive behavioral intervention for tics, METAANALYSIS, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, General Medicine, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Behavior therapy, Pediatrics, Perinatology and Child Health, business, 030217 neurology & neurosurgery
Abstract: Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011–2019 and a manual search for the years 2019–2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.
Published: 2022

11. Lung and diaphragm protective ventilation guided by the esophageal pressure

Author: Davide Chiumello, Martin Dres, Luigi Camporota, dres, martin, Università degli Studi di Milano = University of Milan (UNIMI), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Guy's and St Thomas NHS Foundation Trust [London], and King‘s College London
Subjects: [SDV] Life Sciences [q-bio], Respiration, [SDV]Life Sciences [q-bio], Diaphragm, Humans, Critical Care and Intensive Care Medicine, Lung, Respiration, Artificial
Abstract: International audience; No abstract available
Published: 2022

12. Assessing BRCA1 activity in DNA damage repair using human induced pluripotent stem cells as an approach to assist classification of BRCA1 variants of uncertain significance

Author: Louise Izatt, Michael A. Simpson, Edwige Voisset, Ellen Solomon, Marc Tischkowitz, Meryem Ozgencil, Julian Barwell, Paulo De Sepulveda, Ian Kesterton, Paul T. Sharpe, King‘s College London, University of Leicester, University of Cambridge [UK] (CAM), Guy's and St Thomas NHS Foundation Trust [London], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), De Sepulveda, Paulo, Tischkowitz, Marc [0000-0002-7880-0628], de Sepulveda, Paulo [0000-0001-8295-5414], Voisset, Edwige [0000-0002-0943-4847], and Apollo - University of Cambridge Repository
Subjects: Heredity, DNA Repair, Epidemiology, [SDV]Life Sciences [q-bio], Genetic analysis, Animal Cells, Breast Tumors, Medicine and Health Sciences, Morphogenesis, Induced pluripotent stem cell, Uncertain significance, Connective Tissue Cells, Staining, Heterozygosity, Multidisciplinary, BRCA1 Protein, Stem Cells, Cancer Risk Factors, Cell Staining, Muscle Differentiation, Specimen preparation and treatment, [SDV] Life Sciences [q-bio], Oncology, Connective Tissue, Chromosome abnormality, Medicine, Female, Cellular Types, Anatomy, Research Article, Science, Induced Pluripotent Stem Cells, Genetic Causes of Cancer, Breast Neoplasms, Computational biology, Biology, Breast cancer, Breast Cancer, Genetics, medicine, Homologous chromosome, Humans, Genetic Predisposition to Disease, Genetic Testing, Reporter gene, DAPI staining, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Fibroblasts, medicine.disease, In vitro, Research and analysis methods, Biological Tissue, Medical Risk Factors, Mutation, Nuclear staining, DNA Damage, Developmental Biology
Abstract: Funder: King’s College London, Funder: The European Union Scholarship Programme, Funder: National Institute for Health Research (NIHR), Establishing a universally applicable protocol to assess the impact of BRCA1 variants of uncertain significance (VUS) expression is a problem which has yet to be resolved despite major progresses have been made. The numerous difficulties which must be overcome include the choices of cellular models and functional assays. We hypothesised that the use of induced pluripotent stem (iPS) cells might facilitate the standardisation of protocols for classification, and could better model the disease process. We generated eight iPS cell lines from patient samples expressing either BRCA1 pathogenic variants, non-pathogenic variants, or BRCA1 VUSs. The impact of these variants on DNA damage repair was examined using a ɣH2AX foci formation assay, a Homologous Repair (HR) reporter assay, and a chromosome abnormality assay. Finally, all lines were tested for their ability to differentiate into mammary lineages in vitro. While the results obtained from the two BRCA1 pathogenic variants were consistent with published data, some other variants exhibited differences. The most striking of these was the BRCA1 variant Y856H (classified as benign), which was unexpectedly found to present a faulty HR repair pathway, a finding linked to the presence of an additional variant in the ATM gene. Finally, all lines were able to differentiate first into mammospheres, and then into more advanced mammary lineages expressing luminal- or basal-specific markers. This study stresses that BRCA1 genetic analysis alone is insufficient to establish a reliable and functional classification for assessment of clinical risk, and that it cannot be performed without considering the other genetic aberrations which may be present in patients. The study also provides promising opportunities for elucidating the physiopathology and clinical evolution of breast cancer, by using iPS cells.
Published: 2021

13. Overview of Oral Potentially Malignant Disorders: From Risk Factors to Specific Therapies

Author: Urs Müller-Richter, Coro Bescós Atín, Selvam Thavaraj, Paolo Bossi, Alba de Pablo García-Cuenca, Jorge Pamias Romero, Luigi Lorini, Margarita Alberola Ferranti, Sara Simonetti, Paolo Nuciforo, Manel Sáez Barba, Irene Braña Garcia, Institut Català de la Salut, [Lorini L] Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, ASST Spedali Civili of Brescia, University of Brescia, 25123 Brescia, Italy. [Bescós Atín C, Pamias Romero J, Sáez Barba M, de Pablo García-Cuenca A] Oral and Maxillofacial Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain. [Thavaraj S] Head and Neck Pathology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RS, UK. [Müller-Richter U] Comprehensive Cancer Center and Department of Oral and Maxillofacial Plastic Surgery, University Hospital of Würzburg, 97070 Würzburg, Germany and Bavarian Centre for Cancer Research, 97070 Würzburg, Germany. [Alberola Ferranti M] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Braña García I] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Nuciforo P, Simonetti S] Molecular Oncology Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, diagnóstico::diagnóstico precoz::detección precoz del cáncer [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Disease, Review, Molecular alterations, Morphological features, Oral potentially malignant disorders, Risk factors and etiology, Treatment, Systemic therapy, Malignant transformation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, oral potentially malignant disorders, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell [DISEASES], risk factors and etiology, neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::carcinoma de células escamosas [ENFERMEDADES], ddc:610, molecular alterations, Boca - Càncer - Diagnòstic, Survival rate, RC254-282, Neoplasms::Neoplasms by Site::Head and Neck Neoplasms::Mouth Neoplasms [DISEASES], treatment, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030206 dentistry, Immunotherapy, medicine.disease, Càncer - Detecció precoç, Radiation therapy, stomatognathic diseases, morphological features, 030220 oncology & carcinogenesis, neoplasias::neoplasias por localización::neoplasias de cabeza y cuello::neoplasias de la boca [ENFERMEDADES], business, Diagnosis::Early Diagnosis::Early Detection of Cancer [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract: Simple Summary Oral potentially malignant disorders (OPMDs) include a group of oral mucosal diseases with different morphological characteristics that are able to progress to oral squamous cell carcinoma (OSCC). Given OSCC’s poor prognosis and high mortality, early diagnosis is a priority step in OSCC. Extrinsic and intrinsic risk factors and etiologies are involved in developing and malignant transformation of oral lesions, and different molecular alterations have been described in early lesions associated with a potential malignant behavior. This review summarizes the information about clinical, morphological and molecular features of OPMDs, with an emphasis on the early detection techniques and an overview of the surgical and systemic therapies’ effectiveness. Abstract Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs’ development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combination), has suffered a dramatic change in last years, especially with the introduction of immunotherapy. However, most cases are diagnosed during the advanced stage of the disease, decreasing drastically the survival rate of the patients. Hence, early diagnosis of premalignant conditions (OPMDs) is a priority in oral cancer, as well as a massive education about risk factors, the understanding of mechanisms involved in malignant progression and the development of specific and more efficient therapies. The aim of this article is to review epidemiological, clinical, morphological and molecular features of OPMDs, with the purpose to lay the foundation for an exhaustive comprehension of these lesions and their ability of malignant transformation and for the development of more effective and personalized treatments.
Published: 2021

14. Management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation: a consensus document of the ESC Working Group on Thrombosis and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration with the ESC Council on Valvular Heart Disease

Author: Diana A. Gorog, Erik Lerkevang Grove, Dariusz Dudek, Andrea Rubboli, Julinda Mehilli, Jurriën M. ten Berg, Gemma Vilahur, Julia Grapsa, Lucia Torracca, Bianca Rocca, Adam Witkowski, Anna Sonia Petronio, Eric Van Belle, Patrizio Lancellotti, Jean-Philippe Collet, Dirk Sibbing, Martine Gilard, Bernard Chevalier, Cardiologie, RS: Carim - B04 Clinical thrombosis and Haemostasis, St. Antonius Hospital [Nieuwegein], Ludwig-Maximilians-Universität München [LMU], German Center for Cardiovascular Research [DZHK], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] [Unicatt], Institut Coeur Poumon [CHU Lille], Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011], Hôpital Privé Jacques Cartier [Massy], CHU Pitié-Salpêtrière [AP-HP], Groupe Action, Hôpital de la Cavale Blanche, Université de Brest [UBO], Imperial College London, University of Hertfordshire [Hatfield] [UH], Aarhus University Hospital, Centre Hospitalier Universitaire de Liège [CHU-Liège], University of Pisa - Università di Pisa, Hospital de la Santa Creu i Sant Pau, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Ludwig-Maximilians-Universität München (LMU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), CHU Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), Sorbonne Université (SU), Jagiellonian University - Medical College (JUMC), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Maria Cecilia Hospital [Cotignola], Université de Brest (UBO), University of Hertfordshire [Hatfield] (UH), Guy's and St Thomas' NHS Foundation Trust [London, UK], Centre Hospitalier Universitaire de Liège (CHU-Liège), and National Institute of Cardiology [Varsovie, Pologne]
Subjects: medicine.medical_specialty, Percutaneous, Consensus, Settore BIO/14 - FARMACOLOGIA, [SDV]Life Sciences [q-bio], Heart Valve Diseases, 030204 cardiovascular system & hematology, Lower risk, law.invention, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Antithrombotic treatment, Transcatheter aortic valve implantation, Aged, Aortic Valve, Fibrinolytic Agents, Humans, Treatment Outcome, Aortic Valve Stenosis, Heart Valve Prosthesis Implantation, Thrombosis, Randomized controlled trial, law, Internal medicine, Antithrombotic, medicine, 030212 general & internal medicine, Adverse effect, Aortic Valve/surgery, ANTIPLATELET THERAPY, business.industry, Fibrinolytic Agents/therapeutic use, valvular heart disease, Thrombosis/drug therapy, medicine.disease, Stenosis, Aortic Valve Stenosis/drug therapy, Transcatheter Aortic Valve Replacement/adverse effects, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Transcatheter aortic valve implantation (TAVI) is effective in older patients with symptomatic severe aortic stenosis, while the indication has recently broadened to younger patients at lower risk. Although thromboembolic and bleeding complications after TAVI have decreased over time, such adverse events are still common. The recommendations of the latest 2017 ESC/EACTS Guidelines for the management of valvular heart disease on antithrombotic therapy in patients undergoing TAVI are mostly based on expert opinion. Based on recent studies and randomized controlled trials, this viewpoint document provides updated therapeutic insights in antithrombotic treatment during and after TAVI.
Published: 2021

15. Affordable Three-Dimensional Printed Heart Models

Author: Gorka Gómez-Ciriza, Tomás Gómez-Cía, José Antonio Rivas-González, Mari Nieves Velasco Forte, Israel Valverde, [Gómez-Ciriza,G, Gómez-Cía,T, Rivas-González,JA] Fabrication Laboratory, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (IBIS), Seville, Spain. [Gómez-Cía,T] Plastic Surgery and Burns Unit, Virgen del Rocio University Hospital, Seville, Spain. [Velasco Forte,MN, Valverde,I] Division of Imaging Sciences and Biomedical Engineering, King’s College London, The Rayne Institute, St. Thomas’ Hospital, London, United Kingdom. [Valverde,I] Cardiovascular Pathology Unit, Institute of Biomedicine of Seville (IBIS), Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Hospital Virgen de Rocio/Consejo Superior de Investigaciones Científicas/University of Seville, Seville, Spain. [Valverde,I] Department of Congenital Heart Disease, Evelina London Children’s Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom., This work has been partially funded by Instituto de Salud Carlos III, Spanish Ministry of Health, PI14/00180 3D printed cardiovascular models for congenital heart disease surgical planning, and by Andalusian Ministry of Health PIN-213-2018 3D printing laboratory for the Andalusian Health Service., Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología, and Instituto de Salud Carlos III
Subjects: Medical education, interventional planning, Heart models, Modelos cardiovasculares, Information Science::Information Science::Communication [Medical Subject Headings], Engineering drawing, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Assisted Circulation::Heart-Assist Devices [Medical Subject Headings], affordable 3d printing, Computer science, Process (engineering), education, Procedimientos quirúrgicos vasculares, 3D printing, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Slicing, Surgical planning, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Surgical Equipment::Surgical Mesh [Medical Subject Headings], 030218 nuclear medicine & medical imaging, Impresión tridimensional, Planificación hospitalaria, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], surgical planning, 03 medical and health sciences, 0302 clinical medicine, Diseases::Cardiovascular Diseases::Heart Diseases::Heart Defects, Congenital [Medical Subject Headings], Educación médica, Methods, Diseases of the circulatory (Cardiovascular) system, Image acquisition, Segmentation, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception [Medical Subject Headings], Corazón, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Imaging, Three-Dimensional [Medical Subject Headings], Point (typography), business.industry, Production cost, Affordable 3d printing, Interventional planning, heart models, Technology and Food and Beverages::Technology, Industry, and Agriculture::Technology::Educational Technology::Audiovisual Aids::Models, Structural::Models, Anatomic [Medical Subject Headings], RC666-701, Cardiology and Cardiovascular Medicine, business, medical education
Abstract: This is a 7-years single institution study on low-cost cardiac three-dimensional (3D) printing based on the use of free open-source programs and affordable printers and materials. The process of 3D printing is based on several steps (image acquisition, segmentation, mesh optimization, slicing, and three-dimensional printing). The necessary technology and the processes to set up an affordable three-dimensional printing laboratory are hereby described in detail. Their impact on surgical and interventional planning, medical training, communication with patients and relatives, patients' perception on care, and new cardiac device development was analyzed. A total of 138 low-cost heart models were designed and printed from 2013 to 2020. All of them were from different congenital heart disease patients. The average time for segmentation and design of the hearts was 136 min; the average time for printing and cleaning the models was 13.5 h. The average production cost of the models was €85.7 per model. This is the most extensive series of 3D printed cardiac models published to date. In this study, the possibility of manufacturing three-dimensional printed heart models in a low-cost facility fulfilling the highest requirements from a technical and clinical point of view is demonstrated.
Published: 2021

16. Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

Author: Enrique Grande, A. Loehr, Petros Grivas, Dale L. Nepert, Yohann Loriot, Sumati Gupta, Daleen Thomas, Nicholas J. Vogelzang, Min Yuen Teo, Nabil Adra, Alejo Rodriguez-Vida, Rachel L. Dusek, Simon Chowdhury, S. Srinivas, Yousef Zakharia, Andrew Simmons, Andrea Necchi, Ajjai Alva, Susan Feyerabend, Kenton Wride, Rafael Morales-Barrera, Debra H. Josephs, University of Washington [Seattle], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Passeig Vall d'Hebron [Barcelona, Spain], Memorial Sloane Kettering Cancer Center [New York], University of Iowa [Iowa City], Studienpraxis Urologie [Nürtingen, Germany], Comprehensive Cancer Centers [Las Vegas, NV, USA], MD Anderson Cancer Center [Madrid, Spain], Indiana State University, Department of Internal Medicine and Computational Medicine and Bioinformatics [Ann Arbor, MI, USA], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Human Tumor Immunobiology Unit [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], IMIM-Hospital del Mar, Generalitat de Catalunya, Huntsman Cancer Institute [Salt Lake City], University of Utah, Guy's and St Thomas NHS Foundation Trust [London], Stanford University School of Medicine [CA, USA], Clovis Oncology, Inc. [Boulder, CO, USA], Malbec, Odile, Institut Català de la Salut, [Grivas P] Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA 98109, USA. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Seattle Cancer Care Alliance, Seattle, WA 98109, USA. [Loriot Y] Department of Medicine, Gustave Roussy Cancer Campus, INSERM U981, Université Paris-Saclay, 94800 Villejuif, France. [Morales-Barrera R] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Teo MY] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Zakharia Y] Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA. [Feyerabend S] Studienpraxis Urologie, 72622 Nürtingen, Germany, Vall d'Hebron Barcelona Hospital Campus, Grivas, P., Loriot, Y., Morales-Barrera, R., Teo, M. Y., Zakharia, Y., Feyerabend, S., Vogelzang, N. J., Grande, E., Adra, N., Alva, A., Necchi, A., Rodriguez-Vida, A., Gupta, S., Josephs, D. H., Srinivas, S., Wride, K., Thomas, D., Simmons, A., Loehr, A., Dusek, R. L., Nepert, D., and Chowdhury, S.
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Indoles, DNA Repair, [SDV]Life Sciences [q-bio], Administration, Oral, Loss of Heterozygosity, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Clinical endpoint, Inhibidors enzimàtics - Ús terapèutic - Eficàcia, RC254-282, BRCA1 Protein, Bladder cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Bufeta - Càncer - Tractament, Other subheadings::Other subheadings::/administration & dosage [Other subheadings], Female, Urothelial carcinoma, medicine.symptom, Research Article, medicine.medical_specialty, Metastatic Urothelial Carcinoma, Anemia, Nausea, Urinary Bladder, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Poly(ADP-ribose) Polymerase Inhibitors, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Poly(ADP-ribose) Polymerase Inhibitors [CHEMICALS AND DRUGS], Adverse effect, Rucaparib, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms [DISEASES], Response Evaluation Criteria in Solid Tumors, Aged, BRCA2 Protein, Genomic biomarkers, Carcinoma, Transitional Cell, Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias de la vejiga [ENFERMEDADES], business.industry, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de poli(ADP-ribosa) polimerasas [COMPUESTOS QUÍMICOS Y DROGAS], medicine.disease, PARP inhibitor, 030104 developmental biology, Urinary Bladder Neoplasms, chemistry, business, Follow-Up Studies
Abstract: BackgroundATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).MethodsPatients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks.ResultsOf 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleteriousBRCA1orBRCA2alteration.ConclusionsRucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.Trial registrationThis trial was registered inClinicalTrials.gov(NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017–004166-10).
Published: 2021

17. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanism of olfactory dysfunction in COVID-19 and its association with enhanced survival

Author: Claire Hopkins, Jerome R. Lechien, Sven Saussez, Guy's and St Thomas' NHS Foundation Trust [London, UK], King's College London Guy's Hospital [UK], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Mons [Belgium] (UMONS), Department of Otolaryngology - Head and Neck Surgery, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and We have not received any funding to support this work.
Subjects: 0301 basic medicine, Olfactory system, Olfactory loss, Anosmia, [SDV]Life Sciences [q-bio], Sensory system, Biology, Models, Biological, Severity of Illness Index, T-Lymphocytes, Regulatory, Olfactory Receptor Neurons, Article, 03 medical and health sciences, Olfactory mucosa, Olfaction Disorders, 0302 clinical medicine, Olfactory Mucosa, medicine, Humans, Progenitor cell, Disease severity, COVID, SARS-CoV-2, COVID-19, General Medicine, Virus Internalization, medicine.disease, Magnetic Resonance Imaging, Olfactory Bulb, Neuropilin-1, Olfactory bulb, Smell, 030104 developmental biology, medicine.anatomical_structure, nervous system, Neurotropism, Axoplasmic transport, Neuropilin, Angiotensin-Converting Enzyme 2, medicine.symptom, Cytokine storm, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Three mechanisms have been proposed to account for COVID-19 associated olfactory dysfunction; obstruction of the olfactory cleft; epithelial injury and infection of the sustentacular supporting cells, which are known to express ACE2, or injury to the olfactory bulb due to axonal transport through olfactory sensory neurones. The absence of ACE2 expression by olfactory sensory neurones has led to the neurotropic potential of COVID-19 to be discounted. While an accumulating body of evidence supports olfactory epithelial injury as an important mechanism, this does not account for all the features of olfactory dysfunction seen in COVID-19; for example the duration of loss in some patients, evidence of changes within the olfactory bulb on MRI imaging, identification of viral particles within the olfactory bulb in post-mortem specimens and the inverse association between severity of COVID-19 and the prevalence of olfactory loss. The recent identification of a second route of viral entry mediated by NRP1 addresses many of these inconsistencies. Expression by the olfactory sensory neurones and their progenitor cells may facilitate direct injury and axonal transport to the olfactory bulb as well as a mechanism for delayed or absent recovery. Expression by regulatory T cells may play a central role in the cytokine storm. Variability in expression by age, race or gender may explain differing morbidity of infection and inverse association between anosmia and severity; in the case of higher expression there may be a higher risk of olfactory function but greater activation of regulatory T cells that may suppress the cytokine storm.
Published: 2021
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18. Cystinuria: clinical practice recommendation

Author: Servais, Aude, Thomas, Kay, Dello Strologo, Luca, Sayer, John A, Bekri, Soumeya, Bertholet-Thomas, Aurelia, Bultitude, Matthew, Capolongo, Giovanna, Cerkauskiene, Rimante, Daudon, Michel, Doizi, Steeve, Gillion, Valentine, Gràcia-Garcia, Silvia, Halbritter, Jan, Heidet, Laurence, van den Heijkant, Marleen, Lemoine, Sandrine, Knebelmann, Bertrand, Emma, Francesco, Levtchenko, Elena, Metabolic Nephropathy Workgroup of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Guy's and St Thomas NHS Foundation Trust [London], Children's Hospital Bambino Gesù IRCCS [Rome], University of the Study of Campania Luigi Vanvitelli, Vilnius University [Vilnius], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cliniques Universitaires Saint-Luc [Bruxelles], Fundación Puigvert [Barcelona, Spain], University of Leipzig [Leipzig, Allemagne], University Medical Center [Utrecht], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, Department of Development and Regeneration, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, CarMeN, laboratoire, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] (MARHEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Leipzig University, Servais, Aude, Thomas, Kay, Dello Strologo, Luca, A Sayer, John, Bekri, Soumeya, Bertholet-Thomas, Aurelia, Bultitude, Matthew, Capolongo, Giovanna, Cerkauskiene, Rimante, Daudon, Michel, Doizi, Steeve, Gillion, Valentine, Gràcia-Garcia, Silvia, Halbritter, Jan, Heidet, Laurence, van den Heijkant, Marleen, Lemoine, Sandrine, Knebelmann, Bertrand, Emma, Francesco, and Levtchenko, Elena
Subjects: Adult, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Consensus, Urinary system, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, MEDLINE, potassium citrate, tiopronin, Disease, Kidney, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, cystinuria, medicine, Humans, d-penicillamine, urolithiasis, Child, cystine, Cystinuria, business.industry, D-penicillamine, Evidence-based medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Systematic review, Nephrology, Quality of Life, Cystine, tiopronin and urolithiasis, business
Abstract: Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment. ispartof: KIDNEY INTERNATIONAL vol:99 issue:1 pages:48-58 ispartof: location:United States status: published
Published: 2021

19. Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic : An EAACI statement

Author: Paula Kauppi, Andrea Matucci, Sevim Bavbek, Adam Chaker, Ioana Agache, Davide Firinu, Marek Jutel, Oscar Palomares, Eva Untersmayr, Barbara Rogala, Thomas Eiwegger, Mübeccel Akdis, Onur Boyman, Alexia Chatzipetrou, Susan Chan, Apostolos Bossios, Wojciech Feleszko, Antonios G.A. Kolios, Cezmi A. Akdis, Jean Bousquet, Ludger Klimek, Akash Kothari, Marek L. Kowalski, Oliver Pfaar, Alessandra Vultaggio, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Helsinki University Hospital Area, University of Zurich, Eiwegger, Thomas, Careggi University Hospital [Florence, Italie], Transylvania University of Brasov, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Ankara University School of Medicine [Turkey], Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University hospital of Zurich [Zurich], University Hospital of the Technical University Munich, Guy's and St Thomas NHS Foundation Trust [London], University General Hospital ' Attikon ' [Athens, Greece], Medical University of Warsaw - Poland, University of Cagliari, Wrocław Medical University, ALL-MED Medical Research Institute, Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Centre for Rhinology and Allergy, CHU Montpellier, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), The Hospital for sick children [Toronto] (SickKids), Medical University of Łódź (MUL), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Philipps Universität Marburg = Philipps University of Marburg, Medical University of Silesia (SUM), Medizinische Universität Wien = Medical University of Vienna, University of Toronto, and Salvy-Córdoba, Nathalie
Subjects: 0301 basic medicine, Eaaci Position Paper, Disease, GUIDELINES, IMMUNOLOGY, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 10183 Swiss Institute of Allergy and Asthma Research, Pandemic, MESH: COVID-19, Immunology and Allergy, Nasal polyps, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Academies and Institutes, Atopic dermatitis, 3. Good health, Europe, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2723 Immunology and Allergy, medicine.symptom, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, MESH: Pandemics, medicine.medical_specialty, MESH: Biological Products, MESH: Hypersensitivity, MESH: Academies and Institutes, 610 Medicine & health, Inflammation, 03 medical and health sciences, OMALIZUMAB, medicine, Hypersensitivity, Humans, IGE, Intensive care medicine, Pandemics, Asthma, 2403 Immunology, Biological Products, MESH: Humans, business.industry, Outbreak, COVID-19, medicine.disease, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, 10033 Clinic for Immunology, ASTHMA, MESH: Europe, Cytokine storm, business, RESPONSES
Abstract: International audience; The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
Published: 2020

20. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Daniel R. Barnes, Matti A. Rookus, Lesley McGuffog, Goska Leslie, Thea M. Mooij, Joe Dennis, Nasim Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M. Blanco, Marinus J. Blok, Bernardo Bonanni, Susanne E. Boonen, Åke Borg, Aniko Bozsik, Angela R. Bradbury, Paul Brennan, Carole Brewer, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Lise Lotte Christensen, Wendy K. Chung, Kathleen B.M. Claes, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Antonis Antoniou, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D. Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-ren Ong, Lucy Side, Aoife O’Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Mary B. Daly, Miguel de la Hoya, Robin de Putter, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Cecilia M. Dorfling, Martine Dumont, Bent Ejlertsen, Christoph Engel, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan Friedman, Patricia A. Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Anna González-Neira, Mark H. Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Julia Hentschel, Frans B.L. Hogervorst, Maartje J. Hooning, Judit Horvath, Chunling Hu, Peter J. Hulick, Evgeny N. Imyanitov, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Catherine Noguès, Claudine Isaacs, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Karin Kast, Torben A. Kruse, Ava Kwong, Yael Laitman, Conxi Lazaro, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Jennifer T. Loud, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Austin Miller, Marco Montagna, Semanti Mukherjee, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Laura Papi, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto, Paolo Peterlongo, Georg Pfeiler, Karolina Prajzendanc, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Gad Rennert, Harvey A. Risch, Mark Robson, Karina Rønlund, Ritu Salani, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy E. Side, Christian F. Singer, Thomas P. Slavin, Penny Soucy, Melissa C. Southey, Amanda B. Spurdle, Doris Steinemann, Zoe Steinsnyder, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Darcy L. Thull, Silvia Tognazzo, Amanda E. Toland, Alison H. Trainer, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N. Weitzel, Siddhartha Yadav, Xin Yang, Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J. Couch, Rita K. Schmutzler, Jacques Simard, Douglas F. Easton, Antonis C. Antoniou, Pediatric surgery, Human genetics, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Chapel Allerton Hospital, Great Ormond Street Hospital for Children [London] (GOSH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto (University of Toronto), Christian-Albrechts University of Kiel, The University of Texas M.D. Anderson Cancer Center [Houston], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CIBER de Enfermedades Raras (CIBERER), Spanish National Cancer Research Center (CNIO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Pomeranian Medical University [Szczecin] (PUM), University of California (UC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], European Institute of Oncology IRCCS [Milan, Italy] (EIO), Zealand University Hospital [Roskilde, Denmark], Lund University [Lund], National Institute of Oncology [Budapest, Hungary], Abramson Cancer Center [philadelphia], University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Royal Devon & Exeter Hospital, Exeter, UK, Catalan Institute of Oncology [Barcelone, Espagne], Huntsman Cancer Institute [Salt Lake City], University of Utah, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Pisa University Hospital, Peter MacCallum Cancer Centre [Melbourne, Australie], University of Melbourne, Aarhus University Hospital, Columbia University [New York], Ghent University Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sheffield Children's NHS Foundation Trust, Fox Chase Cancer Center, Queen Elizabeth University Hospital (Glasgow), Centre hospitalier universitaire de Nantes (CHU Nantes), Leiden University Medical Center (LUMC), Beckman Research Institute of the City of Hope, Abramson Cancer Center, University of Pretoria [South Africa], Centre Hospitalier Universitaire de Québec Research Center [Canada], Royal Marsden NHS Foundation Trust, Copenhagen University Hospital, Leipzig University, University of Manchester [Manchester], Manchester Academic Health Science Centre (MAHSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Masaryk Memorial Cancer Institute (MMCI), Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research 'Demokritos' (NCSR), NHMRC Clinical Trials Centre [Camperdown NSW 2050, Australie], Chaim Sheba Medical Center, Tel Aviv University (TAU), Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Dana-Farber Cancer Institute [Boston], University of Würzburg, Rigshospitalet [Copenhagen], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Hospices Civils de Lyon (HCL), University of Kansas [Kansas City], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Medizinische Universität Wien = Medical University of Vienna, University of Cologne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Lancashire NHS Foundation Trust, University Hospital Leipzig, Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Mayo Clinic, NorthShore University HealthSystem [Evanston, IL, USA], The University of Chicago Medicine [Chicago], N. N. Petrov Institute of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Guy's and St Thomas' NHS Foundation Trust [London, UK], Peter MacCallum Cancer Center, East Melbourne, Peter MacCallum Cancer Center, Vilnius University [Vilnius], The State Scientific Research Institute Nature Research Centre, Vilnius, Lithuania, Stanford University School of Medicine [CA, USA], Memorial Sloane Kettering Cancer Center [New York], Cedars-Sinai Medical Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Medical Center [Utrecht], Odense University Hospital [Odense, Denmark], The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Hong Kong Sanatorium and Hospital [Hong Kong] (HKSH), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], 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), David Geffen School of Medicine [Los Angeles], Fondation MINES ParisTech, Karolinska Institutet [Stockholm], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Amsterdam UMC - Amsterdam University Medical Center, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Radboud University Medical Center [Nijmegen], Roswell Park Cancer Institute [Buffalo], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], University of Toronto, University Health Network, University Hospital Düsseldorf, Latvian Biomedical Research and Study Centre [Rīga], 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Chicago, Birmingham Women's and Children's NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), Charité Campus Virchow-Klinikum (CVK), Università degli Studi di Firenze = University of Florence (UniFI), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), Seoul National University [Seoul] (SNU), QIMR Berghofer Medical Research Institute, Aalborg University [Denmark] (AAU), IRCCS Istituto Nazionale dei Tumori [Milano], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Klinikum rechts der Isar [Munich, Germany], University of New South Wales [Sydney] (UNSW), Garvan Institute of medical research, Technion Faculty of Medicine [Haifa, Israel], Yale School of Medicine [New Haven, Connecticut] (YSM), Vejle Hospital [Danemark], Ohio State University [Columbus] (OSU), Centre de lutte contre le cancer Paul-Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas Medical Center [Kansas City, KS, USA], Princess Anne Hospital, City of Hope Comprehensive Cancer Center [Duarte], Monash University [Clayton], Cancer Council Victoria [Melbourne, VIC, Australia], Hannover Medical School [Hannover] (MHH), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Heidelberg University Hospital [Heidelberg], Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Malaysia and University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), McGill University = Université McGill [Montréal, Canada], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Gent = Ghent University (UGENT), Oxford University Hospitals NHS Trust, University of Oxford, Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital of Cologne [Cologne], Mayo Clinic [Rochester], Collaborators : Pascaline Berthet, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Julian Adlard, Munaza Ahmed, Antonis Antoniou, Daniel Barrowdale, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-Ren Ong, Lucy Side, Aoife O'Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Peter Devilee, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Nadine Andrieu, Catherine Noguès, Dupuis, Christine, Institut Català de la Salut, [Barnes DR, McGuffog L, Leslie G, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Rookus MA, Mooij TM] The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Barnes, Daniel [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Mavaddat, Nasim [0000-0003-0307-055X], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI), Medical Oncology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, University of Helsinki, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Pomeranian Medical University, University of California, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Leipzig [Leipzig, Allemagne], Masaryk Memorial Cancer Institute (RECAMO), Tel Aviv University [Tel Aviv], University of California-University of California, University of Münster, Amsterdam UMC, Technical University of Munich (TUM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Garvan Institute of Medical Research [Sydney, Australia], Yale University School of Medicine, Vejle Hospital, University of Kansas Medical Center [Lawrence], Université Paris Descartes (Paris 5), University of Malaya [Kuala Lumpur, Malaisie], Universiteit Gent = Ghent University [Belgium] (UGENT), and University of Oxford [Oxford]
Subjects: 0301 basic medicine, Oncology, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], [SDV]Life Sciences [q-bio], Càncer d'ovari, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], MODIFIERS, Diàtesi, SUSCEPTIBILITY, Carcinoma, Ovarian Epithelial, PRS, 0302 clinical medicine, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Medicine and Health Sciences, Medicine, Genetics(clinical), genetics, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], BRCA1 Protein, Hazard ratio, Absolute risk reduction, 1184 Genetics, developmental biology, physiology, article, ASSOCIATION, neoplasias::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas::carcinoma epitelial de ovario [ENFERMEDADES], ddc, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Heterozygote, Population, 3122 Cancers, Single-nucleotide polymorphism, Breast Neoplasms, MUTATION CARRIERS, Ovaris - Càncer - Aspectes genètics, Càncer de mama, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, Ovarian cancer, BRCA1/2, Internal medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], BRCA2 Protein, IDENTIFICATION, business.industry, Neoplasms::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms::Carcinoma, Ovarian Epithelial [DISEASES], Retrospective cohort study, ALLELES, medicine.disease, BRCA1, BRCA2, MODEL, PATHOLOGY, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, 3111 Biomedicine, business
Abstract: Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access) PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Published: 2020

21. A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group

Author: Zain Kassam, Alexander Link, Eero Mattila, Chris J. J. Mulder, Josbert J. Keller, Christoph Högenauer, Ed J. Kuijper, Maurizio Sanguinetti, Gianluca Laniro, Maria J G T Vehreschild, Elisabeth M. Terveer, Ajit Sood, Patrizia Kump, Simon D. Goldenberg, Oleksiy Gridnyev, Simon Mark Dahl Baunwall, Olena Gubska, Giovanni Cammarota, Simone C. Lieberknecht, Cyriel Y. Ponsioen, Francis Mégraud, Andrey Dorofeev, Shiv Kumar Sarin, Antonio Gasbarrini, Reetta Satokari, Herbert Tilg, Christian Lodberg Hvas, Horace R T Williams, Rogier E. Ooijevaar, Laurent Alric, Radislav Nakov, Hein W. Verspaget, Abraham Goorhuis, Ramesh P. Arasaradnam, Georgina L. Hold, Lorenza Putignani, Perttu Arkkila, Sergiy Tkatch, Juozas Kupcinskas, Harry Sokol, Megraud, Francis, Haaglanden Medical Center [La Haye, Pays-Bas] (HMC), Leiden University Medical Center (LUMC), University of Amsterdam [Amsterdam] (UvA), Aarhus University Hospital, Frankfurt University Hospital, Medical University Graz, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Group of Fecal Microbiota Transplantation [Paris] (GFTF), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Tsaritsa Yoanna University Hospital = Queen Giovanna University Hospital [Sofia], King‘s College London, Guy's and St Thomas NHS Foundation Trust [London], Ukranian Scientific and Practical Center of Endocrine Surgery [Kyiv], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Medical Academy of Postgraduate Education n.a. P.L. Shupic [Kiev], Bogomolets national medical university, University Hospital Coventry Warwickshire (UHCW), University Hospital Coventry, Institute of Liver and Biliary Sciences [New Delhi], Dayanand Medical College and Hospital [Ludhiana], IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), VU University Medical Center [Amsterdam], Lithuanian University of health Sciences [Kaunas], Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Leids Universitair Medisch Centrum [Leiden], University of New South Wales [Sydney] (UNSW), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Finch Therapeutics Group, ESCMID Study Group for Host and Microbiota Interaction [Basel] (ESGHAMI), Imperial College London, University of Cologne, German Centre for Infection Research (DZIF), University of Helsinki, Tsaritsa Yoanna University Hospital [Sofia], Fondazione Policlinico Universitario Agostino Gemelli IRCCS [Rome], Fondazione Policlinico Universitario Agostino Gemelli [Rome], CHU Toulouse [Toulouse], Otto-von-Guericke University [Magdeburg] (OVGU), Innsbruck Medical University [Austria] (IMU), Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, HUS Abdominal Center, Department of Medicine, Clinicum, Gastroenterologian yksikkö, Reetta Maria Satokari / Principal Investigator, HUMI - Human Microbiome Research, Research Programs Unit, Faculty of Medicine, and HUS Internal Medicine and Rehabilitation
Subjects: Quality Assurance, Health Care, Small Bowel, Fecal microbiota transplantation, Feces, 0302 clinical medicine, fluids and secretions, Recurrence, Procedure, Multidisciplinary approach, stool bank, Medicine, 030212 general & internal medicine, faecal microbiota transplantation, Biological Specimen Banks, Informed Consent, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microbiota, Clostridium infections, microbiology, therapy, Clostridium difficile, isolation&purification, Donor selection, Consensus, digestive, oral, and skin physiology, Age Factors, Gastroenterology, 3. Good health, Oncology, Original Article, 030211 gastroenterology & hepatology, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, legislation, Faecal microbiota transplantation, Donor Selection, Specimen Handling, Contraindications, Procedure, Immunocompromised Host, 03 medical and health sciences, Internal medicine, Humans, business.industry, Clostridioides difficile, Contraindications, Settore MED/09 - MEDICINA INTERNA, Fecal bacteriotherapy, Health Care, Transplantation, 3121 General medicine, internal medicine and other clinical medicine, Clostridium Infections, 616.9-022.363. [udc], Quality Assurance, business, Clostridioides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.
Published: 2020

22. Trials on oxygen supplementation in sepsis: better late than never

Author: Audrey De Jong, Anders Perner, Manu Shankar-Hari, Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Copenhagen University Hospital, 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), Guy's and St Thomas' NHS Foundation Trust, London, SE17EH, UK., School of Immunology and Microbial Sciences, Kings College, London, SE1 9RT, UK, and MORNET, Dominique
Subjects: Oxygen inhalation therapy, medicine.medical_specialty, Oxygen supplementation, business.industry, Pain medicine, [SDV]Life Sciences [q-bio], MEDLINE, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, medicine.disease, Sepsis, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Respiration, medicine, 030212 general & internal medicine, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

23. Permanent prostate brachytherapy: Dosimetric results and analysis of a learning curve with a dynamic dose-feedback technique

Author: Beaney, Ronald [Department of Clinical Oncology, Guy's and St. Thomas' NHS Foundation Trust, London (United Kingdom)]
Published: 2006
Full Text: View/download PDF

24. ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases

Author: Asterios Kampouras, Sarah Crook, Jana De Brandt, Richard Casaburi, Danilo C. Berton, Zafeiris Louvaris, Roberto A Rabinovich, Pierantonio Laveneziana, Martijn A. Spruit, Georgios Kaltsakas, Yvonne M J Goërtz, Helge Hebestreit, Ioannis Vogiatzis, Milo A. Puhan, Jeanette Boyd, Sauwaluk Dacha, J. Alberto Neder, Samuel Verges, Frits M.E. Franssen, Don S. Urquhart, Dimitris Kontopidis, Thomy Tonia, Ernst Eber, Thierry Troosters, Dionne C.W. Braeken, Chris Burtin, Thomas Radtke, Daniel Langer, Pulmonologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Afdeling Onderwijs FHML, University of Zurich, Hebestreit, Helge, Universität Zürich [Zürich] = University of Zurich (UZH), University hospital of Zurich [Zurich], Guy's and St Thomas' NHS Foundation Trust [London, UK], National and Kapodistrian University of Athens (NKUA), University Hospitals Leuven [Leuven], Technologie campus Gent - KU Leuven (KU Leuven), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Royal Hospital for Sick Children [Edinburgh], 424 General Military Training Hospital [Thessaloniki, Greece] (424 GMTH), University of Edinburgh, Royal Infirmary of Edinburgh, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Hellenic Cystic Fibrosis Association [Athens, Greece] (HCFA), The European Lung Foundation (ELF), University of Bern, Hasselt University (UHasselt), CIRO [Horn, The Netherlands], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Chiang Mai University (CMU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Medical University of Graz, University Hospital Gasthuisberg [Leuven], Queen's University [Kingston, Canada], Harbor UCLA Medical Center [Torrance, Ca.], University of Northumbria at Newcastle [United Kingdom], University Hospital of Würzburg, and SALAS, Danielle
Subjects: Lung Diseases, [SDV]Life Sciences [q-bio], Medical Physiology, Respiratory System, PULSE-OXIMETRY, 030204 cardiovascular system & hematology, Cochrane Library, 0302 clinical medicine, Clinical Protocols, Medicine, Treadmill, 610 Medicine & health, Lung, Cardiopulmonary exercise testing, [SDV] Life Sciences [q-bio], Europe, VISUAL ANALOG SCALES, Respiratory, NONINVASIVE ASSESSMENT, 360 Social problems & social services, Recovery phase, Pulmonary and Respiratory Medicine, medicine.medical_specialty, MEDLINE, RESPIRATORY GAS-EXCHANGE, Work rate, OBSTRUCTIVE PULMONARY-DISEASE, 03 medical and health sciences, Clinical Research, Humans, lcsh:RC705-779, Task force, business.industry, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), lcsh:Diseases of the respiratory system, HEART-RATE RECOVERY, C600, PHYSIOLOGICAL-RESPONSES, SCIENTIFIC STATEMENT, 030228 respiratory system, 2740 Pulmonary and Respiratory Medicine, Chronic Disease, Physical therapy, Exercise Test, Diagnostic assessment, OXYGEN-UPTAKE, business, MAXIMAL VOLUNTARY VENTILATION
Abstract: The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data. Funding was received from the European Respiratory Society, grant number TF-2016-12. The research of Jana De Brandt is financially supported by FWO (grant #11B4718N) and the research of Chris Burtin is partially sponsored by Limburg Kankerfonds. Funding information for this article has been deposited with the Crossref Funder Registry. Hebestreit, H (reprint author), Univ Kinderklin, ERN LUNG, Josef Schneider Str 2, D-97080 Wurzburg, Germany. hebestreit@uni-wuerzburg.de
Published: 2019

25. Visualization of coronary arteries in paediatric patients using whole-heart coronary magnetic resonance angiography: comparison of image-navigation and the standard approach for respiratory motion compensation

Author: Srinivas Ananth Narayan, Israel Valverde, Reza Razavi, Kuberan Pushparajah, Tarique Hussain, Nanda Prabhu, Markus Henningsson, Teresa Correia, Aaron Bell, Sujeev Mathur, Mari Nieves Velasco Forte, Instituto de Biomedicina de Sevilla (IBIS), [Velasco Forte,MN, Valverde,I, Correia,T, Narayan,SA, Razavi,R, Hussain,T, Pushparajah,K, Henningsson,M] Division of Biomedical Engineering and Imaging Sciences, King's College London, London, UK. [Velasco Forte,MN, Prabhu,N, Bell,A, Mathur,S, Pushparajah,K] Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London, UK. [Velasco Forte,MN, Valverde,I] Cardiovascular Pathology Unit, Institute of Biomedicine of Seville, IBIS, Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain. [Hussain,T] Department of Pediatrics, University of Texas Southwestern Medical Center, 1935 Medical District Drive, Dallas, USA. [Henningsson,M] Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden., and This work was supported by the National Institute for Health Research (NIHR) Cardiovascular Healthcare Technology Cooperative (HTC) and Biomedical Research Centre (BRC) awarded to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London. This work was additionally supported by the Wellcome/EPSRC Centre for Medical Engineering at King’s College London [WT 088641/Z/09/Z) as well as the BHF Centre of Excellence (British Heart Foundation award RE/08/03).
Subjects: Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Time Factors, Image quality, Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings], Respiratory motion compensation, Contrast Media, Image-based navigation, Coronary artery disease, Magnetic resonance angiography, Workflow, 030218 nuclear medicine & medical imaging, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Respiratory Physiological Phenomena::Respiratory Physiological Processes::Respiration [Medical Subject Headings], Child, Information Science::Information Science::Systems Analysis::Workflow [Medical Subject Headings], Persons::Persons::Age Groups::Infant [Medical Subject Headings], Radiological and Ultrasound Technology, medicine.diagnostic_test, Respiration, Anatomy::Cardiovascular System::Blood Vessels::Arteries::Coronary Vessels [Medical Subject Headings], Coronary Vessels, 3. Good health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], medicine.anatomical_structure, Child, Preschool, Right coronary artery, Chemicals and Drugs::Organic Chemicals::Organometallic Compounds [Medical Subject Headings], Female, Artifacts, Cardiology and Cardiovascular Medicine, Artery, Radiology, Nuclear Medicine and Medical Imaging, Heart Defects, Congenital, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging::Magnetic Resonance Imaging, Cine [Medical Subject Headings], medicine.medical_specialty, Adolescent, Enfermedad de la arteria coronaria, Check Tags::Male [Medical Subject Headings], Magnetic Resonance Imaging, Cine, Diaphragmatic breathing, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], 03 medical and health sciences, Meglumine, Predictive Value of Tests, medicine.artery, Organometallic Compounds, medicine, Humans, Persons::Persons::Age Groups::Child [Medical Subject Headings], Radiology, Nuclear Medicine and imaging, Angiology, Coronary magnetic resonance angiography, Chemicals and Drugs::Organic Chemicals::Alcohols::Sugar Alcohols::Sorbitol::Meglumine [Medical Subject Headings], business.industry, Research, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Artifacts [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Cardiovascular::Angiography::Magnetic Resonance Angiography [Medical Subject Headings], Infant, Reproducibility of Results, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Diagnostic Uses of Chemicals::Contrast Media [Medical Subject Headings], medicine.disease, Coronary arteries, Check Tags::Female [Medical Subject Headings], lcsh:RC666-701, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Reproducibility of Results [Medical Subject Headings], Angiografía por resonancia magnética, Diseases::Cardiovascular Diseases::Cardiovascular Abnormalities::Heart Defects, Congenital [Medical Subject Headings], Radiologi och bildbehandling, business, Nuclear medicine, Persons::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], Magnetic Resonance Angiography
Abstract: AimsTo investigate the use of respiratory motion compensation using image-based navigation (iNAV) with constant respiratory efficiency using single end-expiratory thresholding (CRUISE) for coronary magnetic resonance angiography (CMRA), and compare it to the conventional diaphragmatic navigator (dNAV) in paediatric patients with congenital or suspected heart disease.MethodsiNAV allowed direct tracking of the respiratory heart motion and was generated using balanced steady state free precession startup echoes. Respiratory gating was achieved using CRUISE with a fixed 50% efficiency. Whole-heart CMRA was acquired with 1.3mm isotropic resolution. For comparison, CMRA with identical imaging parameters were acquired using dNAV. Scan time, visualization of coronary artery origins and mid-course, imaging quality and sharpness was compared between the two sequences.ResultsForty patients (13 females; median weight: 44kg; median age: 12.6, range: 3months-17years) were enrolled. 25 scans were performed in awake patients. A contrast agent was used in 22 patients. The scan time was significantly reduced using iNAV for awake patients (iNAV 7:481:26 vs dNAV 9:48 +/- 3:11, P=0.01) but not for patients under general anaesthesia (iNAV=6:55 +/- 1:50 versus dNAV=6:32 +/- 2:16; P=0.32). In 98% of the cases, iNAV image quality had an equal or higher score than dNAV. The visual score analysis showed a clear difference, favouring iNAV (P=0.002). The right coronary artery and the left anterior descending vessel sharpness was significantly improved (iNAV: 56.8%+/- 10.1% vs dNAV: 53.7%+/- 9.9%, Pamp;lt;0.002 and iNAV: 55.8%+/- 8.6% vs dNAV: 53%+/- 9.2%, P=0.001, respectively).Conclusion p id=Par4 iNAV allows for a higher success-rate and clearer depiction of the mid-course of coronary arteries in paediatric patients. Its acquisition time is shorter in awake patients and image quality score is equal or superior to the conventional method in most cases. Funding Agencies|National Institute for Health Research (NIHR) Cardiovascular Healthcare Technology Cooperative (HTC); Biomedical Research Centre (BRC); Kings College London; Wellcome/EPSRC Centre for Medical Engineering at Kings College London [WT 088641/Z/09/Z]; BHF Centre of Excellence (British Heart Foundation) [RE/08/03]
Published: 2019

26. European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD

Author: Jean-Louis Pépin, Raffaele Scala, Manel Luján, Bram Rochwerg, Jeanette Boyd, Annalisa Carlucci, Wolfram Windisch, Mark W. Elliott, Lara Pisani, Jésus Gonzalez-Bermejo, Jan Hendrik Storre, Nicholas Hart, Michelle Chatwin, Enrico Clini, Simon Oczkowski, Thomy Tonia, Stefano Nava, Peter J. Wijkstra, Jacek Nasiłowski, Begüm Ergan, Ergan B., Oczkowski S., Rochwerg B., Carlucci A., Chatwin M., Clini E., Elliott M., Gonzalez-Bermejo J., Hart N., Lujan M., Nasilowski J., Nava S., Pepin J.L., Pisani L., Storre J.H., Wijkstra P., Tonia T., Boyd J., Scala R., Windisch W., Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), McMaster University [Hamilton, Ontario], Istituti Clinici Scientifici Maugeri [Pavia] (IRCCS Pavia - ICS Maugeri), Royal Brompton Hospital, University - Hospital of Modena and Reggio Emilia [Modena, Italy], St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Guy's and St Thomas' NHS Foundation Trust [London, UK], King‘s College London, Universitat Autònoma de Barcelona (UAB), Medical University of Warsaw - Poland, Alma Mater Studiorum University of Bologna (UNIBO), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Groningen [Groningen], University of Bern, The European Lung Foundation (ELF), Civile - M.P.Arezzo Hospital, Universität Witten Herdecke, and SALAS, Danielle
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MEDLINE, Context (language use), OBSTRUCTIVE PULMONARY-DISEASE, CARBON-DIOXIDE, copd NONINVASIVE VENTILATION META-ANALYSIS GUIDELINES, medicine, Respiratory system, HIGH-INTENSITY, Intensive care medicine, Mechanical ventilation, RANDOMIZED CROSSOVER TRIAL, COPD, POSITIVE-PRESSURE VENTILATION, business.industry, STABLE HYPERCAPNIC COPD, NASAL VENTILATION, Evidence-based medicine, PHYSIOLOGICAL EVALUATION, medicine.disease, MECHANICAL VENTILATION, [SDV] Life Sciences [q-bio], Breathing, medicine.symptom, business, Hypercapnia, DIFFERENT MODES
Abstract: BackgroundWhile the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients.Materials and methodsThe European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients.ResultsThe task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode.ConclusionsManaging hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.
Published: 2019

27. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Author: Christian F. Singer, Louise Izatt, Yen Y. Tan, Emmanuelle Mouret-Fourme, Embrace, Genepso, Bcfr, Hebon, kConFab, Marie Navratilova, Lucy Side, Trinidad Caldés, Rosemarie Davidson, Kelly-Anne Phillips, Saundra S. Buys, Dominique Leroux, Mary B. Daly, Melissa C. Southey, Marian J.E. Mourits, Brita Arver, Theo A. M. van Os, Anne-Marie Gerdes, Douglas F. Easton, Marie-José Roos-Blom, Michael Friedlander, Lieske H. Schrijver, David E. Goldgar, Anna Jakubowska, Roger L. Milne, Håkan Olsson, Lisa Walker, Ros Eeles, Flora E. van Leeuwen, Mary Porteous, Sue-Anne McLachlan, Pascaline Berthet, Lenka Foretova, Catherine Noguès, Matti A. Rookus, Debra Frost, Daniel Barrowdale, Esther M. John, Julian Adlard, Encarna B. Gomez Garcia, Nadine Andrieu, Laurence Venat-Bouvet, Anita Bane, John L. Hopper, Mary Beth Terry, Jacques Simard, Ana Osorio, Antonis C. Antoniou, Christoph Engel, Wendy K. Chung, Karin Kast, Ibccs, D. Gareth Evans, Valérie Bonadona, Edith Olah, Steve Ellis, Christi J. van Asperen, T.M. Mooij, Human Genetics, APH - Methodology, APH - Quality of Care, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Skane University Hospital [Lund], Lund University [Lund], University of Melbourne, Columbia Mailman School of Public Health, University of Utah School of Medicine [Salt Lake City], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Department of Clinical Sciences [Lund], University of Leipzig [Leipzig, Allemagne], Chapel Allerton Hospital, University of Cambridge [UK] (CAM), Queen Elizabeth University Hospital (Glasgow), Royal Marsden NHS Foundation Trust, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Western General Hospital [Edinburgh, UK], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire [Grenoble] (CHU), hôpital couple-enfant [CHU Grenoble Alpes], Hôpital René HUGUENIN (Saint-Cloud), Hôpital Dupuytren [CHU Limoges], Huntsman Cancer Institute [Salt Lake City], University of Utah, Monash University [Melbourne], Stanford University School of Medicine [CA, USA], California Sciences Institute, Columbia University [New York], Fox Chase Cancer Center, McMaster University [Hamilton, Ontario], Karolinska Institutet [Stockholm], Leiden University Medical Center (LUMC), School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center Groningen [Groningen] (UMCG), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, St. Vincent's Hospital, Sydney, Medizinische Universität Wien = Medical University of Vienna, Masaryk Memorial Cancer Institute (RECAMO), University Hospital of Cologne [Cologne], Copenhagen University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Université Laval [Québec] (ULaval), National Institute of Oncology [Budapest, Hungary], Pomeranian Medical University [Szczecin, Poland] (PMU), Spanish National Cancer Centre, 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), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], Melbourne School for Population and Global Health-University of Melbourne, Leipzig University, Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Masaryk Memorial Cancer Institute (MMCI), Pomeranian Medical University [Szczecin] (PUM), Mines Paris - PSL (École nationale supérieure des mines de Paris), University of Melbourne-Melbourne School for Population and Global Health, Malbec, Odile, Universiteit Leiden, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Life Course Epidemiology (LCE), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, OVARIAN-CANCER, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Prospective cohort study, skin and connective tissue diseases, Pregnancy, Proportional hazards model, Obstetrics, business.industry, Hazard ratio, CONSORTIUM, WOMEN, medicine.disease, PREVENTION, Confidence interval, KCONFAB, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, Cohort study
Abstract: Background For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed. Results For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002). Conclusions Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.
Published: 2018

28. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota

Author: Glenn R. Gibson, Thomas Aranias, Julien Chilloux, Lesley Hoyles, Dominique Gauguier, Antonis Myridakis, Francois Brial, Jeremy D. Sanderson, Anne L. McCartney, Christophe Magnan, Jeremy K. Nicholson, Marc-Emmanuel Dumas, M.L. Jiménez-Pranteda, 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), Commission of the European Communities, Medical Research Council, Medical Research Council (MRC), Imperial College London, University of Reading (UOR), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Guy's and St Thomas' NHS Foundation Trust [London, UK], King‘s College London, and ORANGE, Colette
Subjects: Male, Magnetic Resonance Spectroscopy, HIGH-FAT DIET, Gut-liver axis, [SDV]Life Sciences [q-bio], Microbial metabolism, URINARY, Trimethylamine, Trimethylamine N-oxide, Gut flora, GLUCOSE, chemistry.chemical_compound, Tandem Mass Spectrometry, PHOSPHATIDYLCHOLINE, Co-metabolic axis, Lactic acid bacteria, Chromatography, High Pressure Liquid, In Situ Hybridization, Fluorescence, 0303 health sciences, biology, INDUCED OBESITY, Enterobacteriaceae, Lactic acid, L-CARNITINE, [SDV] Life Sciences [q-bio], Biochemistry, ESCHERICHIA-COLI, Metabolome, lcsh:QR100-130, Female, Life Sciences & Biomedicine, Adult, DIET-INDUCED OBESITY, ANAEROBIC RESPIRATION, FATE, Microbiology, digestive system, lcsh:Microbial ecology, Methylamines, 03 medical and health sciences, IMPAIRED GLUCOSE-TOLERANCE, INTESTINAL MICROBIOTA, Animals, Humans, Metabolomics, Gut–liver axis, 030304 developmental biology, Science & Technology, Bacteria, IDENTIFICATION, 030306 microbiology, Research, biology.organism_classification, Gastrointestinal Microbiome, MICE, chemistry, Fermentation, CHOLINE
Abstract: BACKGROUNDThe dietary methylamines choline, carnitine and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes.RESULTSA feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO, but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture.CONCLUSIONSReduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium.Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.
Published: 2018

29. Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL)

Author: Nicolas Lévy, Sahar Elouej, Jean-Pierre Desvignes, Christophe Béroud, Shehla Mohammed, Richard Caswell, Ana Beleza-Meireles, Kevin Colclough, Annachiara De Sandre-Giovannoli, Sian Ellard, Génétique Médicale et Génomique Fonctionnelle (GMGF), 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)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical Genetics [London, UK], Guy's and St Thomas' NHS Foundation Trust [London, UK], Institute of Biomedical and Clinical Science [Exeter, UK], University of Exeter Medical School [UK], Department of Molecular Genetics [Exeter, UK], Royal Devon and Exeter NHS Foundation Trust [UK], Département de génétique médicale [Hôpital de la Timone - APHM], 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), 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 National de la Recherche Scientifique (CNRS), University of Exeter, 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), and DESVIGNES, Jean-Pierre
Subjects: 0301 basic medicine, Premature aging, Male, Lipodystrophy, Endocrinology, Diabetes and Metabolism, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Deafness, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Bioinformatics, Barrier to autointegration factor 1, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Germline mutation, Progeria, Sequence Analysis, Protein, medicine, Missense mutation, Humans, Exome, Age of Onset, Child, Exome sequencing, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], DNA Polymerase III, Genetics, POLD1, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Exons, Syndrome, medicine.disease, 3. Good health, Mandibuloacral dysplasia, 030104 developmental biology, ERCC8, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, ZnF2, Whole-exome sequencing, Mutation, Female, MDPL syndrome, POLD1 gene, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, Gene Deletion
Abstract: Background Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Twelve unrelated patients carried a recurrent in-frame deletion of a single codon (p.Ser605del) and two other patients carried a novel heterozygous mutation in exon 13 (p.Arg507Cys). Additionally and interestingly, germline mutations of the same gene have been involved in familial polyposis and colorectal cancer (CRC) predisposition. Patients and Methods We describe a male and a female patient with MDPL respectively affected with mild and severe phenotypes. Both of them showed mandibular hypoplasia, a beaked nose with bird-like facies, prominent eyes, a small mouth, growth retardation, muscle and skin atrophy, but the female patient showed such a severe and early phenotype that a first working diagnosis of Hutchinson-Gilford Progeria was made. The exploration was performed by direct sequencing of POLD1 gene exon 15 in the male patient with a classical MDPL phenotype and by whole exome sequencing in the female patient and her unaffected parents. Results Exome sequencing identified in the latter patient a de novo heterozygous undescribed mutation in the POLD1 gene (NM_002691.3: c.3209T > A), predicted to cause the missense change p.Ile1070Asn in the ZnF2 (Zinc Finger 2) domain of the protein. This mutation was not reported in the 1000 Genome Project, dbSNP and Exome sequencing databases. Furthermore, the Isoleucine1070 residue of POLD1 is highly conserved among various species, suggesting that this substitution may cause a major impairment of POLD1 activity. For the second patient, affected with a typical MDPL phenotype, direct sequencing of POLD1 exon 15 revealed the recurrent in-frame deletion (c.1812_1814del, p.S605del). Conclusion Our work highlights that mutations in different POLD1 domains can lead to phenotypic variability, ranging from dominantly inherited cancer predisposition syndromes, to mild MDPL phenotypes without lifespan reduction, to very severe MDPL syndromes with major premature aging features. These results also suggest that POLD1 gene testing should be considered in patients presenting with severe progeroid features.
Published: 2017

30. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition

Author: Beverley J. Hunt, Radko Komadina, Timothy J Coats, Vladimir Cerny, Arthur Schultz, Yves Ozier, Enrique Fernández-Mondéjar, Jean Louis Vincent, Jacques Duranteau, Giuseppe Nardi, Daniela Filipescu, Louis Riddez, Rolf Rossaint, Donat R. Spahn, Edmund Neugebauer, Bertil Bouillon, University of Zurich, Spahn, Donat R, [Rossaint,R] Department of Anaesthesiology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. [Bouillon,B] Department of Trauma and Orthopaedic Surgery, Witten/Herdecke University, Cologne-Merheim Medical Centre, Cologne, Germany. [Cerny,V] Department of Anaesthesiology, Perioperative Medicine and Intensive Care, J.E. Purkinje University, Masaryk Hospital, Usti nad Labem, Czech Republic. Department of Research and Development, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic. Department of Anaesthesiology and Intensive Care, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic. Department of Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, QE II Health Sciences Centre, Halifax, Canada. [Coats,TJ] Emergency Medicine Academic Group, University of Leicester, Leicester, UK. [Duranteau,J] Department of Anaesthesia and Intensive Care, Hôpitaux Universitaires Paris Sud, University of Paris, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, Cedex, France. [Fernández-Mondéjar,E] Servicio de Medicina Intensiva, Complejo Hospitalario Universitario de Granada, Granada, Spain. [Filipescu,D] Department of Cardiac Anaesthesia and Intensive Care, C. C. Iliescu Emergency Institute of Cardiovascular Diseases, Bucharest, Romania. [Hunt,BJ] King’s College, Departments of Haematology, Pathology and Lupus, Guy’s and St Thomas’ NHS Foundation Trust,London, UK. [Komadina,R] Department of Traumatology, General and Teaching Hospital Celje, Celje, Slovenia. [Nardi,G] Shock and Trauma Centre, S. Camillo Hospital, Rome, Italy. [Neugebauer,EAM] Faculty of Health - School of Medicine, Witten/Herdecke University, Cologne, Germany. [Ozier,Y] Division of Anaesthesia, Intensive Care and Emergency Medicine, Brest University Hospital, Brest, France. [Riddez,L] Department of Surgery and Trauma, Karolinska University Hospital, Solna, Sweden. [Schultz,A] Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Lorenz Boehler Trauma Centre, Vienna, Austria. [Vincent,JL] Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. [Spahn,DR] Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland., and The development of this guideline was initiated and performed by the authors as members of the Task Force for Advanced Bleeding Care in Trauma. Members of the task force were compensated for their presence at one face-to-face meeting, but not for the time invested in developing and reviewing the recommendations or manuscript. Meeting organisation and medical writing support for literature searches and manuscript preparation were provided by Physicians World Europe GmbH (Mannheim, Germany). Costs incurred for medical writing support, travel, hotel accommodation, meeting facilities, honoraria and publication were supported by unrestricted grants from CSL Behring GmbH (Marburg, Germany) and LFB Biomédicaments (Courtaboeuf, France).
Subjects: Guiding Principles, Trastornos de la coagulación sanguínea, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Coagulation Disorders [Medical Subject Headings], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Scientific evidence, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Hemorragia, Disease management (health), Metas, Resucitación, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Anticoagulants [Medical Subject Headings], Evidence-Based Medicine, Algoritmos, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Disease Management, Health Care::Health Services Administration::Organization and Administration::Safety Management [Medical Subject Headings], Blood Coagulation Disorders, Humanos, Europe, Consenso, Health Care::Health Care Quality, Access, and Evaluation::Quality Assurance, Health Care::Guidelines as Topic [Medical Subject Headings], Centros Traumatológicos, Medical emergency, Safety management systems, 2706 Critical Care and Intensive Care Medicine, medicine.medical_specialty, Phenomena and Processes::Mathematical Concepts::Algorithms [Medical Subject Headings], 10216 Institute of Anesthesiology, 610 Medicine & health, Guidelines as Topic, Hemorrhage, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Hemorrhage [Medical Subject Headings], Permissive hypotension, Health Care::Health Care Economics and Organizations::Social Control, Formal::Jurisprudence::Expert Testimony [Medical Subject Headings], 03 medical and health sciences, Testimonio de experto, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Motivation::Goals [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Emergency Treatment::Resuscitation [Medical Subject Headings], medicine, Humans, Europa (Continente), Emergency Treatment, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Group Processes::Consensus [Medical Subject Headings], business.industry, Research, Généralités, 030208 emergency & critical care medicine, Evidence-based medicine, Guideline, medicine.disease, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Administration::Hospital Departments::Emergency Service, Hospital::Trauma Centers [Medical Subject Headings], Anticoagulantes, Clinical trial, Emergency medicine, Wounds and Injuries, Guías como asunto, business, Gestión de la seguridad
Abstract: Background: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. Results: The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. Conclusions: A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2016

31. Testing Validity of the MOGAD Diagnostic Criteria in Children and Adults.

Author: Rossor T and Hacohen Y
Subjects: Adult, Child, Humans, Inflammation diagnosis, Central Nervous System Diseases diagnosis, Immune System Diseases diagnosis
Published: 2024
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32. BASHH UK guidelines for the management of syphilis 2024.

Author: Kingston M, Apea V, Evans C, Fifer H, Foster K, Patrick P, Grant A, Manns V, Ramsden S, Sinka K, Sukthankar A, Sullivan A, and Tyler S
Abstract: The 2024 UK guidelines for the management of syphilis are in line with current evidence and practice within the UK. Key updates are detailed at the start of the article. These guidelines are accompanied by the first UK guidelines for the management of syphilis in pregnant people and children, 2024., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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33. Correction: Mechanical power ratio threshold for ventilator-induced lung injury.

Author: D'Albo R, Pozzi T, Nicolardi RV, Galizia M, Catozzi G, Ghidoni V, Donati B, Romitti F, Herrmann P, Busana M, Gattarello S, Collino F, Sonzogni A, Camporota L, Marini JJ, Moerer O, Meissner K, and Gattinoni L
Published: 2024
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34. Ethical debates amidst flawed healthcare artificial intelligence metrics.

Author: Gallifant J, Bitterman DS, Celi LA, Gichoya JW, Matos J, McCoy LG, and Pierce RL
Published: 2024
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35. Codesign of a Quality Improvement Tool for Adults With Prolonged Critical Illness: A Modified Delphi Consensus Study.

Author: Allum L, Pattison N, Connolly B, Apps C, Cowan K, Flowers E, Hart N, and Rose L
Subjects: Humans, Adult, United Kingdom, Intensive Care Units standards, Female, Male, Length of Stay, Surveys and Questionnaires, Middle Aged, Critical Care standards, Critical Care methods, Delphi Technique, Critical Illness therapy, Quality Improvement, Consensus
Abstract: Objectives: Increasing numbers of patients experience a prolonged stay in intensive care. Yet existing quality improvement (QI) tools used to improve safety and standardize care are not designed for their specific needs. This may result in missed opportunities for care and contribute to worse outcomes. Following an experience-based codesign process, our objective was to build consensus on the most important actionable processes of care for inclusion in a QI tool for adults with prolonged critical illness., Design: Items were identified from a previous systematic review and interviews with former patients, their care partners, and clinicians. Two rounds of an online modified Delphi survey were undertaken, and participants were asked to rate each item from 1 to 9 in terms of importance for effective care; where 1-3 was not important, 4-6 was important but not critical, and 7-9 was critically important for inclusion in the QI tool. A final consensus meeting was then moderated by an independent facilitator to further discuss and prioritize items., Setting: Carried out in the United Kingdom., Patients/subjects: Former patients who experienced a stay of over 7 days in intensive care, their family members and ICU staff., Interventions: None., Measurements and Main Results: We recruited 116 participants: 63 healthcare professionals (54%), 45 patients (39%), and eight relatives (7%), to Delphi round 1, and retained 91 (78%) in round 2. Of the 39 items initially identified, 32 were voted "critically important" for inclusion in the QI tool by more than 70% of Delphi participants. These were prioritized further in a consensus meeting with 15 ICU clinicians, four former patients and one family member, and the final QI tool contains 25 items, including promoting patient and family involvement in decisions, providing continuity of care, and structured ventilator weaning and rehabilitation., Conclusions: Using experience-based codesign and rigorous consensus-building methods we identified important content for a QI tool for adults with prolonged critical illness. Work is underway to understand tool acceptability and optimum implementation strategies., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
Published: 2024
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36. A Mysterious Rash Following Cardiothoracic Surgery: A Not So Sweet Ending.

Author: Daoud A, Rajani R, Androshchuk V, and Montarello N
Abstract: A male in his 70s, with a recent history of aortic valve replacement, mitral valve repair, and permanent pacemaker implantation (PPM), developed a fever, raised inflammatory markers, and a disseminated rash. Despite being attributed a diagnosis of an unspecified connective tissue disorder and erythema nodosum at his local hospital, his symptoms continued to deteriorate. A subsequent urgent admission was arranged to his original cardiothoracic centre for the exclusion of infective endocarditis (IE). Although this was subsequently ruled out by echocardiography and microbiological evaluation, a diagnosis of Sweet syndrome (SS) was made following a punch biopsy of a skin lesion. This was later attributed to myelodysplastic syndrome following a bone marrow biopsy. In this report, we firstly describe our diagnostic algorithm for reaching this diagnosis and the characteristic skin lesions associated with this condition. We furthermore review the history of SS, its known associations, and treatment options., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Daoud et al.)
Published: 2024
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37. Acquired motor speech disorders in childhood epilepsy.

Author: Eyre M, Rose S, Gwynn R, Pressler RM, and Clark M
Abstract: Aim: To evaluate a group of children with epilepsy and motor speech regression, with the aim of characterizing their speech disorders, electrographic features, and outcomes., Method: Children referred to a tertiary developmental epilepsy clinic with epilepsy and motor speech regression were identified retrospectively. A clinical history was taken, and longitudinal speech and cognitive data were recorded. Speech samples were scored for severity and speech features. Seizure frequency and epileptiform discharges in the interictal electroencephalogram were analysed., Results: Eighteen children (10 female) were evaluated, including seven with Landau-Kleffner syndrome and six with Rasmussen syndrome. Speech regression occurred at a mean age of 5 years (SD = 2 years 6 months), which was concurrent with seizure onset or peak seizure burden in eight children. Speech features included dysarthria (n = 13), phonological errors (n = 7), and dyspraxia (n = 6). Electrographic abnormalities occurred most frequently in the left centrotemporal and right frontal regions. Among children who were followed up, intelligibility of speech was affected in 13 at baseline and seven at follow-up (p = 0.03). Expressive language standardized scores increased from a mean (SD) of 50.0 (11.3) to 91.4 (27.8) in children with Landau-Kleffner syndrome (mean change = 41.4, 95% confidence interval [CI] 0.04-82.8, p = 0.0498) and decreased from 75.2 (15.3) to 59.0 (9.8) in children with Rasmussen syndrome (mean change -16.2, 95% CI -9.0 to -23.4, p = 0.002) over the follow-up., Interpretation: Motor speech disorders in epilepsy were severe, multifarious, and often fluctuated with seizure burden. Symptoms typically improved, especially in children with Landau-Kleffner syndrome, but rarely fully resolved., (© 2024 Mac Keith Press.)
Published: 2024
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38. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis.

Author: Gerds AT, Harrison C, Kiladjian JJ, Mesa R, Vannucchi AM, Komrokji R, Bose P, Kremyanskaya M, Mead AJ, Gotlib J, Rose S, Sanabria F, Marsousi N, Giuseppi AC, Jiang H, Palmer JM, McCaul K, Ribrag V, and Passamonti F
Subjects: Humans, Female, Male, Aged, Middle Aged, Treatment Outcome, Activin Receptors, Type II therapeutic use, Aged, 80 and over, Pyrazoles therapeutic use, Pyrazoles adverse effects, Anemia drug therapy, Anemia etiology, Primary Myelofibrosis drug therapy, Primary Myelofibrosis complications, Recombinant Fusion Proteins therapeutic use, Recombinant Fusion Proteins adverse effects, Immunoglobulin Fc Fragments therapeutic use, Immunoglobulin Fc Fragments adverse effects
Abstract: Abstract: The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Published: 2024
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39. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial.

Author: Harrison CN, Mesa R, Talpaz M, Al-Ali HK, Xicoy B, Passamonti F, Palandri F, Benevolo G, Vannucchi AM, Mediavilla C, Iurlo A, Kim I, Rose S, Brown P, Hernandez C, Wang J, and Kiladjian JJ
Abstract: Background: Most patients with myelofibrosis develop ruxolitinib intolerance or disease that is relapsed or refractory, and survival rates after ruxolitinib discontinuation are poor. We aimed to evaluate the safety and efficacy of fedratinib versus best available therapy (BAT) in patients with myelofibrosis previously treated with ruxolitinib., Methods: FREEDOM2 was a multicentre, open-label, randomised, controlled, phase 3 trial in 86 clinics in 16 countries, in which patients aged at least 18 years with intermediate-2 or high-risk myelofibrosis that was relapsed or refractory or intolerant to ruxolitinib with Eastern Cooperative Oncology Group performance status 0-2 were stratified by spleen size by palpation, platelet count, and previous ruxolitinib treatment, and randomly assigned 2:1 by interactive response technology to receive fedratinib 400 mg per day (4 × 100 mg capsules orally once daily, open-label) or BAT. Patients received prophylactic antiemetics and thiamine supplementation, and symptomatic antidiarrhoeals as required. Primary endpoint was proportion of patients reaching spleen volume reduction (SVR) of at least 35% (SVR35) at end of cycle 6 in the intention-to-treat population. This manuscript reports the primary analysis of the trial; follow-up is ongoing. This trial is registered at clinicaltrials.gov, NCT03952039., Findings: Between Sept 9, 2019 and June 24, 2022, of 316 patients screened, 201 were randomly assigned and treated (134 to fedratinib, 67 to BAT [including 52 receiving ruxolitinib]); 46 patients from the BAT group crossed over to fedratinib. Approximately half of enrolled patients were male (fedratinib 75 [56%] of 134; BAT 30 [45%] of 67) and most were White (fedratinib 106 [79%] of 134; BAT 58 [87%] of 67). At data cutoff (Dec 27, 2022), median survival follow-up was 64·5 weeks (IQR 37·9-104·9). SVR35 at end of cycle 6 was seen in 48 (36%) of 134 patients receiving fedratinib versus four (6%) of 67 patients receiving BAT (30% difference; 95% CI 20-39; one-sided p-value <0·0001). During the first six cycles 53 (40%) of 134 patients in the fedratinib group and 8 (12%) of 67 patients in the BAT group had grade 3 or greater treatment-related adverse events, most frequently anaemia (fedratinib 12 [9%] of 134; BAT 6 [9%] of 67) and thrombocytopenia (fedratinib 16 [12%] of 134; BAT 2 [3%] of 67); one patient in the fedratinib group died from acute kidney injury suspected to be related to study drug (no treatment-related deaths in the BAT group). Gastrointestinal adverse events occurred more frequently in the fedratinib group compared with the BAT group, but were mostly grade 1-2 in severity and more frequent in early cycles, and were less frequent than in prior clinical trials. A total of 28 (21%) of 134 patients in the fedratinib group and 3 (4%) of 67 patients in the BAT group had thiamine levels below lower limit of normal per central laboratory assessment, with only one case of low thiamine in the fedratinib arm after the introduction of prophylactic thiamine supplementation., Interpretation: Findings from FREEDOM2 support fedratinib as a second-line Janus kinase inhibitor option to reduce spleen size after ruxolitinib failure or intolerance in patients with myelofibrosis, and shows effective strategies for management of gastrointestinal adverse events and low thiamine concentrations through prophylaxis, monitoring, and treatment., Funding: Bristol Myers Squibb., Competing Interests: Declaration of interests CNH reports research funding from Bristol Myers Squibb, Constellation–Morphosys, and Novartis; consulting fees from Galecto, Geron, and GlaxoSmithKline; honoraria from AbbVie, AOP Health, Bristol Myers Squibb–Celgene, CTI BioPharma, Galacteo, Geron, Gilead, IMAGO, Janssen, Keros, Novartis, Promedior, Roche, Shire, and Sierra; participation on a data safety monitoring board or advisory board with Galacteo and Keros; and leadership at the European Hematology Association. RM reports honoraria from AbbVie, Blueprint, Bristol Myers Squibb, CTI BioPharma, Genentech, Geron, GlaxoSmithKline, Incyte, Morphosys, Novartis, Sierra Oncology, and Telios. MT reports research funding from Bristol Myers Squibb; travel support from Sumitomo; participation on a data safety monitoring board or advisory board with Bristol Myers Squibb, Novartis, and Sumitomo; and leadership in the Society of Hematologic Oncology. HKA-A reports research funding from Bristol Myers Squibb, Incyte, and Novartis; travel support from AbbVie and Bristol Myers Squibb; and participation on a data safety monitoring board or advisory board with AbbVie, AOP Health, Blueprint, Bristol Myers Squibb, Novartis, and SGK. FPas reports research funding from Bristol Myers Squibb–Celgene; consulting fees from AbbVie, AOP Health, Bristol Myers Squibb–Celgene, Kartos, Karyopharma, Kyowa Kirin–MEI, Novartis, Roche, Sierra Oncology, and Sumitomo; and honoraria from AbbVie, AOP Health, Bristol Myers Squibb–Celgene, Novartis, and Roche. FPal reports research funding from Bristol Myers Squibb; honoraria from AbbVie, Amgen, AOP Health, Bristol Myers Squibb, CTI BioPharma, GlaxoSmithKline, Kartos, Novartis, and Telios; travel support from AbbVie and Novartis; and participation on a data safety monitoring board or advisory board with AbbVie, AOP Health, Bristol Myers Squibb, CTI BioPharma, GlaxoSmithKline, and Novartis. GB reports honoraria and participation on a data safety monitoring board or advisory board with Bristol Myers Squibb, Janssen, and Novartis. AMV reports honoraria from AbbVie, Bristol Myers Squibb, Geron, GlaxoSmithKline, Incyte, and Novartis; and participation on a data safety monitoring board or advisory board with Bristol Myers Squibb, Geron, Incyte, and Novartis. CM reports research funding from AbbVie and Bristol Myers Squibb; and honoraria from AbbVie, Bristol Myers Squibb, and Novartis. AI reports honoraria from Bristol Myers Squibb, GlaxoSmithKline, Incyte, Novartis, and Pfizer; and participation on a data safety monitoring board or advisory board with AOP Health, Bristol Myers Squibb, Incyte, Novartis, and Pfizer. PB reports employment and stock or stock options with Bristol Myers Squibb. CH reports employment with Bristol Myers Squibb. SR reports employment and stock or stock options with Bristol Myers Squibb. JW reports employment with Bristol Myers Squibb. J-JK reports consulting fees from AbbVie and GlaxoSmithKline; honoraria from AOP Health and Novartis; and participation on a data safety monitoring board or advisory board with Bristol Myers Squibb and Incyte. BX and IK report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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40. Iron replacement in anthracycline-related cardiac dysfunction: fuel on the fire?

Author: Nazir MS, Lyon AR, and Southworth R
Subjects: Humans, Iron adverse effects, Cardiotoxicity etiology, Anthracyclines adverse effects
Published: 2024
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41. An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024.

Author: Ardern-Jones MR, Brown SJ, Flohr C, Hossain P, Irvine AD, Johnston GA, Lane M, Langan SM, Laws P, O'Driscoll D, O'Kane D, Payne A, Petrof G, Pink AE, Rauz S, Robbie S, Gore SK, Shah M, Woolf RT, Wang C, Tumbeva S, and Mohd Mustapa MF
Abstract: Background: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise., Objectives: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD)., Methods: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on., Results: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications., Conclusions: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab., (© British Association of Dermatologists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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42. A Prognostic Model to Predict Hearing Recovery in Patients With Idiopathic Sudden Onset Sensorineural Hearing Loss.

Author: Mandavia R, Joshi N, Hannink G, Ahmed MN, Parmar D, Di Bonaventura S, Gomes P, Iqbal I, Lyles J, Schilder AGM, and Mehta N
Abstract: Importance: The prognosis of idiopathic sudden onset sensorineural hearing loss (iSSNHL) is uncertain, which creates challenges in clinical decision-making for ear, nose, and throat (ENT) physicians and adds to the burden of the condition experienced by patients., Objective: To develop and internally validate a prognostic model for hearing recovery among patients with iSSNHL to support ENT surgeons in making informed and individualized treatment decisions., Design, Settings, and Participants: This prognostic study and model used cohort data from the Sudden Onset Sensorineural Hearing Loss study, which included 812 patients (age ≥16 years) diagnosed with iSSNHL at 76 National Health Service ENT departments in the UK from December 2019 to May 2022. Nine variables previously reported as independent prognostic factors for complete recovery of patients with iSSNHL were selected for inclusion. The final model was internally validated using bootstrapping with 500 repetitions, then coefficients were adjusted for the degree of optimism in the model. The model intercept was reassessed after adjustment of model coefficients. Impact of individual predictors was evaluated by estimating odds ratios with corresponding 95% CIs. Model performance was re-evaluated after internal validation and expressed by discrimination, calibration, and clinical utility. Data analyses were performed from March 2022 to April 2024., Intervention: Routine treatment (per National Health Service standards), including oral steroids and intratympanic steroid injections., Main Outcome and Measures: Complete hearing recovery defined as a return to within 10 dB of the patient's before iSSNHL hearing levels at all frequencies in the affected ear at 6 to 16 weeks after iSSNHL symptom onset., Results: The study sample included 498 patients (mean [SD] age, 58.7 [16.0] years; 215 [46.9%] females and 243 [53.1%] males) who met the criteria for inclusion in the model. Of those, 210 (46%) were classified as having experienced complete hearing recovery. Five variables were found to be independent predictors for complete hearing recovery: steroid treatment within 7 days from symptom onset (OR, 5.23 vs no treatment ), lower severity of hearing loss at presentation (OR, 0.19 if loss is mild), absence of vertigo (OR, 0.56 vs no vertigo), younger patient age (OR, 0.64 per year), and a history of cardiovascular disease (OR, 1.84 vs no cardiovascular disease). The model showed good performance after internal validation with a c-index of 0.77 (95% CI, 0.7-0.81). Predictions for complete recovery aligned well with observed complete recovery rates, and greater clinical utility than treat all or treat none strategies was shown., Conclusion and Relevance: This prognostic model evaluated in this study may be able to assist ENT surgeons in making informed treatment decisions for individual patients with iSSNHL. It is available online at no cost.
Published: 2024
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43. Deep learning method with integrated invertible wavelet scattering for improving the quality of in vivo cardiac DTI.

Author: Deng Z, Wang L, Kuai Z, Chen Q, Ye C, Scott AD, Nielles-Vallespin S, and Zhu Y
Subjects: Signal-To-Noise Ratio, Humans, Wavelet Analysis, Heart diagnostic imaging, Heart physiology, Diastole, Diffusion Tensor Imaging methods, Deep Learning, Image Processing, Computer-Assisted methods
Abstract: Objective. Respiratory motion, cardiac motion and inherently low signal-to-noise ratio (SNR) are major limitations of in vivo cardiac diffusion tensor imaging (DTI). We propose a novel enhancement method that uses unsupervised learning based invertible wavelet scattering (IWS) to improve the quality of in vivo cardiac DTI. Approach. Our method starts by extracting nearly transformation-invariant features from multiple cardiac diffusion-weighted (DW) image acquisitions using multi-scale wavelet scattering (WS). Then, the relationship between the WS coefficients and DW images is learned through a multi-scale encoder and a decoder network. Using the trained encoder, the deep features of WS coefficients of multiple DW image acquisitions are further extracted and then fused using an average rule. Finally, using the fused WS features and trained decoder, the enhanced DW images are derived. Main result. We evaluate the performance of the proposed method by comparing it with several methods on three in vivo cardiac DTI datasets in terms of SNR, contrast to noise ratio (CNR), fractional anisotropy (FA), mean diffusivity (MD) and helix angle (HA). Comparing against the best comparison method, SNR/CNR of diastolic, gastric peristalsis influenced, and end-systolic DW images were improved by 1%/16%, 5%/6%, and 56%/30%, respectively. The approach also yielded consistent FA and MD values and more coherent helical fiber structures than the comparison methods used in this work. Significance. The ablation results verify that using the transformation-invariant and noise-robust wavelet scattering features enables us to effectively explore the useful information from the limited data, providing a potential mean to alleviate the dependence of the fusion results on the number of repeated acquisitions, which is beneficial for dealing with the issues of noise and residual motion simultaneously and therefore improving the quality ofinvivocardiac DTI. Code can be found inhttps://github.com/strawberry1996/WS-MCNN., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
Published: 2024
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44. Oral and dental health promotion for children's nurses.

Author: Najim S, Ali M, and Bhujel N
Subjects: Humans, Dental Caries prevention & control, Child, Breast Feeding methods, Oral Hygiene methods, Oral Hygiene standards, Nurses, Pediatric, Toothbrushing methods, Infant, Health Promotion methods, Oral Health standards
Abstract: Tooth decay remains one of the most common preventable oral health concerns in children. After birth, advice to caregivers predominantly focuses on medical health with little attention paid to dental health. Before discharge from the maternity unit and during future hospital and community appointments, opportunistic dental advice should be provided by midwives, nurses and health visitors where possible, with the aim of preventing early onset dental disease. Registering with a dentist at birth is crucial due to long NHS dental waiting lists. Simple advice on toothbrushing should be offered, including brushing twice a day with a soft toothbrush using an age-appropriate amount of fluoride toothpaste. Mothers should be provided with information on the benefits of breastfeeding for oral health alongside tailored preventive care. Appropriate advice on bottle-feeding and weaning is required, including minimising the use of added sugar, drinking from free-flow cups after six months of age, and discouraging the use of milk bottles at bedtime and in general after one year of age. Written visual summaries can be shared with parents to consolidate verbal advice on oral and dental health., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)
Published: 2024
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45. Tocilizumab in acute necrotizing encephalopathy (ANE): How much, how soon, and will it improve outcomes beyond survival?

Author: Han VX and Lim M
Published: 2024
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46. Risk Stratification in Older Intensively Treated Patients With AML.

Author: Versluis J, Metzner M, Wang A, Gradowska P, Thomas A, Jakobsen NA, Kennedy A, Moore R, Boertjes E, Vonk CM, Kavelaars FG, Rijken M, Gilkes A, Schwab C, Beverloo HB, Manz M, Visser O, Van Elssen CHMJ, de Weerdt O, Tick LW, Biemond BJ, Vekemans MC, Freeman SD, Harrison CJ, Cook JA, Dennis M, Knapper S, Thomas I, Craddock C, Ossenkoppele GJ, Löwenberg B, Russell N, Valk PJM, and Vyas P
Abstract: Purpose: AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment., Methods: We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRI-AML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215)., Results: The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated TP53 (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% ± 4%, intermediate: 38% ± 2%, poor: 21% ± 2%, very poor: 4% ± 1%; [2] 54% ± 9%, 43% ± 4%, 27% ± 4%, 4% ± 3%; and [3] 54% ± 10%, 33% ± 6%, 14% ± 5%, 0% ± 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT., Conclusion: The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT.
Published: 2024
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47. The association of vascular loops within the internal auditory meatus or contacting the vestibulo-cochlear nerve with audio-vestibular symptoms. A systematic review and meta-analysis.

Author: Cowen JE, Tehrani MS, and Connor SE
Abstract: Background: Intrameatal vascular loops (IVL) entering the internal auditory meatus (IAM) and neurovascular contact (NVC) with the vestibulo-cochlear nerve (CN VIII) have been proposed to have a relationship with audio-vestibular symptoms., Purpose: This systematic review and meta-analysis aimed to determine whether the presence of IVLs and CN VIII NVC on magnetic resonance imaging (MRI) is associated with tinnitus, sensorineural hearing loss (SNHL) or vertigo and any specific subtypes., Data Sources: All studies comparing the presence of IVL or CN VIII NVC in ears with these audio-vestibular symptoms and controls were identified through MEDLINE, EMBASE, Web of Science Core Collection, Scopus and Cochrane Register of Controlled Trials databases., Study Selection: 16 studies and 3,455 ears (1526 symptomatic ears and 1929 control ears) were included., Data Analysis: Meta-analysis was performed using a bivariate random effects model. Pooled odds ratios (ORs) were calculated, and heterogeneity was evaluated with Cochran's Q test with statistical significance defined as p<0.05., Data Synthesis: There was no significant association between the presence of undefined tinnitus or SNHL and that of IVL (OR 0.90 95% CI 0.47, 1.70; OR 0.67, 95% CI 0.36, 1.25) or CN VIII NVC (OR 1.15, 95% CI 0.68, 1.95; OR 0.89, 95% CI 0.33, 2.40). However, the subgroup of sudden onset SNHL was associated with IVL (OR 1.34, 95% CI 1.04, 1.73) (p=0.02). There was no significant difference in the prevalence of IVL (OR 0.97, 95% CI 0.64, 1.48) or CN VIII NVC (OR 0.99, 95% CI 0.42, 2.32) between ears with undefined vertigo and control ears. However, there was an association between the presence of CN VIII NVC and the specific diagnosis of vestibular paroxysmia (OR 13.19, 95% CI 2.09, 83.16) (p=0.006)., Limitations: Our meta-analysis is limited by selection bias, small number of eligible studies and moderate heterogeneity., Conclusions: IVL or CN VIII NVC on MRI are unrelated to symptoms of undefined tinnitus, SNHL and vertigo. However, CN VIII NVC is associated with vestibular paroxysmia whilst IVL is associated with sudden onset SNHL., Abbreviations: AICA = anterior inferior cerebellar artery, CI = confidence interval, CN = cranial nerve, CPA = cerebellopontine angle, IAM = internal auditory meatus, NVC = neurovascular contact, OR = odds ratio, SNHL = sensorineural hearing loss, SoSNHL = sudden onset sensorineural hearing loss., (© 2024 by American Journal of Neuroradiology.)
Published: 2024
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48. Eftilagimod Alpha (Soluble LAG3 Protein) Combined with Pembrolizumab as Second-Line Therapy for Patients with Metastatic Head and Neck Squamous Cell Carcinoma.

Author: Forster M, Brana I, Pousa AL, Doger B, Roxburgh P, Bajaj P, Peguero J, Krebs M, Carcereny E, Patel G, Mueller C, Brignone C, and Triebel F
Subjects: Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck pathology, Squamous Cell Carcinoma of Head and Neck mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Lymphocyte Activation Gene 3 Protein, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms pathology, Antigens, CD
Abstract: Purpose: Eftilagimod alpha (efti), a soluble LAG3 protein, activates antigen-presenting cells (APC) and downstream T cells. TACTI-002 (part C) evaluated whether combining efti with pembrolizumab led to strong antitumor responses in patients with second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) while demonstrating good tolerability., Patients and Methods: In this multinational phase II trial using Simon's two-stage design, patients who were PD-L(1)-naïve with R/M HNSCC who had failed first-line platinum-based therapy, unselected for PD-L1, received intravenous pembrolizumab (200 mg, once every 2 weeks) combined with subcutaneous efti (30 mg once every 2 weeks for 24 weeks and once every 3 weeks thereafter). The primary endpoint was objective response rate per RECIST 1.1 modified for immune-based therapy by investigator assessment. Additional endpoints included duration of response, progression-free survival, overall survival, and tolerability. Pharmacodynamic effects (absolute lymphocyte count) and Th1 cytokine biomarkers (IFNγ/CXCL10)] were evaluated in liquid biopsies., Results: Between March 2019 and January 2021, 39 patients were enrolled; 37 were evaluated for response. All patients received prior chemotherapy, and 40.5% were pretreated with cetuximab; 53.1% of patients had PD-L1 combined positive score <20. With a median follow-up of 38.8 months, the objective response rate was 29.7%, including 13.5% complete responders. The median duration of response was not reached. Rapid and sustained absolute lymphocyte count increase was observed in patients who had an objective response. Th1 biomarkers increased sustainably after first treatment. No unexpected safety signals were observed., Conclusions: Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in patients with second-line head and neck squamous cell carcinoma (HNSCC), thus supporting further evaluation of this combination in earlier treatment lines., (©2024 American Association for Cancer Research.)
Published: 2024
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49. Real-World Analysis of Survival and Treatment Efficacy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

Author: Josephides E, Dunn R, Henry AR, Pilling J, Harrison-Phipps K, Patel A, Ahmad S, Skwarski M, Spicer J, Georgiou A, Ghosh S, Van Hemelrijck M, Karapanagiotou E, Smith D, and Bille A
Abstract: Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials., Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed., Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups ( p = 0.99)., Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.
Published: 2024
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50. Clinical cases referring to the 2023 EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ.

Author: Czerny M, Berger T, Della Corte A, Kreibich M, Lescan M, Mestres CA, Quintana E, Rylski B, Schönhoff F, Czerny M, Grabenwöger M, Berger T, Aboyans V, Della Corte A, Chen EP, Desai N, Dumfarth J, Elefteriades JA, Etz CD, Kim KM, Kreibich M, Lescan M, Di Marco L, Martens A, Mestres CA, Milojevic M, Nienaber CA, Piffaretti G, Preventza O, Quintana E, Rylski B, Schlett CL, Schoenhoff F, Trimarchi S, and Tsagakis K
Subjects: Humans, Acute Disease, Chronic Disease, Aortic Diseases diagnosis, Aortic Diseases therapy, Male, Female, Syndrome, Practice Guidelines as Topic
Abstract: Clinical cases referring to the EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ aim to assist physicians in selecting the best management strategies for individual patients with a given condition. These expert opinions consider the impact on patient outcomes as well as the risk-benefit ratio of different diagnostic or therapeutic methods. These cases serve as a vital tool to aid physicians in making decisions in their daily practice. However, in essence, although these recommendations serve as a valuable resource to guide clinical practice, their application should be tailored to the needs of the individual patient. Each patient's case is unique, presenting its own set of variables and circumstances. This editorial is a tool designed to support, but not supersede, the decision-making process of physicians, based on their knowledge, expertise and understanding of their patients' individual situations. Furthermore, these clinical cases are based on the EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ but should not be interpreted as legally binding documents. The legal responsibilities of healthcare professionals remain firmly grounded in applicable laws and regulations, and the guidelines and the clinical cases presented in this document do not alter these obligations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
Published: 2024
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