Institution
Guy's and St Thomas' NHS Foundation Trust
Healthcare•London, United Kingdom•
About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.
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University of Cape Town1, Guy's and St Thomas' NHS Foundation Trust2, University College London3, University of Würzburg4, University of Pennsylvania5, Newcastle University6, Robert Jones and Agnes Hunt Orthopaedic Hospital7, University of Michigan8, University of Cambridge9, University of Basel10, King's College London11
TL;DR: This work investigated whether RYR1 mutations cause CNM, a rare congenital myopathy characterized by prominence of central nuclei on muscle biopsy that has been associated with mutations in MTM1, DNM2, and BIN1.
Abstract: Objective: Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by prominence of central nuclei on muscle biopsy. CNM has been associated with mutations in MTM1, DNM2, and BIN1 but many cases remain genetically unresolved. RYR1 encodes the principal sarcoplasmic reticulum calcium release channel and has been implicated in various congenital myopathies. We investigated whether RYR1 mutations cause CNM. Methods: We sequenced the entire RYR1 coding sequence in 24 patients with a diagnosis of CNM from South Africa (n ¼ 14) and Europe (n ¼ 10) and identified mutations in 17 patients. The most common genotypes featured compound heterozygosity for RYR1 missense mutations and mutations resulting in reduced protein expression, including intronic splice site and frameshift mutations. Results: The high incidence in South African patients (n ¼ 12/14) in conjunction with recurrent RYR1 mutations associated with common haplotypes suggested the presence of founder effects. In addition to central nuclei, prominent histopathological findings included (often multiple) internalized nuclei and t ype 1f iber predominance and hypotrophy with relative type 2 hypertrophy. Although cores were not typically seen on oxidative stains, electron microscopy revealed subtle abnormalities in most cases. External ophthalmoplegia, proximal weakness, and bulbar involvement were prominent clinical findings. Interpretation: Our findings expand the range of RYR1-related phenotypes and suggest RYR1 mutations as a common cause of congenital myopathies with central nuclei. Corresponding to recent observations in X-linked CNM, these findings indicate disturbed assembly and/or malfunction of the excitation-contraction machinery as a key mechanism in CNM and related myopathies. ANN NEUROL 2010;68:717–726
236 citations
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University of Paris1, Ghent University Hospital2, Medical University of Vienna3, University of Lisbon4, Autonomous University of Barcelona5, Technische Universität München6, Guy's and St Thomas' NHS Foundation Trust7, King's College London8, University of Gothenburg9, Utrecht University10, Humanitas University11
TL;DR: The COVID-19 pandemic has had an overwhelming psychological impact on intensivists and follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
Abstract: The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence of burnout syndrome amongst intensivists facing the COVID-19 outbreak. Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model. Response rate was 20% (1001 completed questionnaires were returned, 45 years [39–53], 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 [1.33–2.55]), working in a university-affiliated hospital (HR 0.58 [0.42–0.80]), living in a city of > 1 million inhabitants (HR 1.40 [1.01–1.94]), and clinician’s rating of the ethical climate (HR 0.83 [0.77–0.90]). Independent determinants of depression included female gender (HR 1.63 [1.15–2.31]) and clinician’s rating of the ethical climate (HR 0.84 [0.78–0.92]). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year [0.97–0.99]) and clinician’s rating of the ethical climate (HR 0.76 [0.69–0.82]). The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
235 citations
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TL;DR: Data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factors.
Abstract: Upon detection of antigen, CD4+ T helper (Th) cells can differentiate into a number of effector types that tailor the immune response to different pathogens Alternative Th1 and Th2 cell fates are specified by the transcription factors T-bet and GATA-3, respectively Only a handful of target genes are known for these two factors and because of this, the mechanism through which T-bet and GATA-3 induce differentiation toward alternative cell fates is not fully understood Here, we provide a genomic map of T-bet and GATA-3 binding in primary human T cells and identify their target genes, most of which are previously unknown In Th1 cells, T-bet associates with genes of diverse function, including those with roles in transcriptional regulation, chemotaxis and adhesion GATA-3 occupies genes in both Th1 and Th2 cells and, unexpectedly, shares a large proportion of targets with T-bet Re-complementation of T-bet alters the expression of these genes in a manner that mirrors their differential expression between Th1 and Th2 lineages These data show that the choice between Th1 and Th2 lineage commitment is the result of the opposing action of T-bet and GATA-3 at a shared set of target genes and may provide a general paradigm for the interaction of lineage-specifying transcription factors
234 citations
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University of Oxford1, University of Bristol2, University of Exeter3, University of Aberdeen4, Maimonides Medical Center5, Radboud University Nijmegen6, St George's, University of London7, Macquarie University8, Guy's and St Thomas' NHS Foundation Trust9, University of Minnesota10, Cornell University11
TL;DR: This article updates and extends the IDEAL Recommendations, identifies areas for future research, and discusses the ethical problems faced by investigators at each IDEAL stage, to widen the practical use of IDEAL.
Abstract: Objective:To update, clarify, and extend IDEAL concepts and recommendations.Background:New surgical procedures, devices, and other complex interventions need robust evaluation for safety, efficacy, and effectiveness. Unlike new medicines, there is no internationally agreed evaluation pathway for gen
234 citations
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University of Cambridge1, Hospital Sant Joan de Déu Barcelona2, Guy's and St Thomas' NHS Foundation Trust3, Boston Children's Hospital4, University of Lyon5, Medical University of Warsaw6, Ghent University Hospital7, University Hospitals Bristol NHS Foundation Trust8, Glenfield Hospital9, King's College London10
TL;DR: Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.
Abstract: Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystem inflammatory syndrome (MIS-C) associated with COVID-19 infection. Methods: A real-time internet-based survey endorsed by the Association for European Paediatric and Congenital Cardiologists (AEPC) Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Inclusion criteria was children 0-18 years admitted to hospital between February 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (IQR 3.8-12.4 years) and 67% were males. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients and a vast majority of children had raised cardiac troponin (cTnT) when checked. The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP, serum ferritin, procalcitonin, NT-proBNP, IL-6 level and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need for intensive care support (p <0.05). Polymerase chain reaction (PCR) for SARS-CoV-2 was positive in 33.6% while IgM and IgG antibodies were positive in 15.7% and IgG 43.6 % cases, respectively when checked. One child died in the study cohort. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with Covid-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.
234 citations
Authors
Showing all 7765 results
Name | H-index | Papers | Citations |
---|---|---|---|
Christopher J L Murray | 209 | 754 | 310329 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Giuseppe Remuzzi | 172 | 1226 | 160440 |
Mika Kivimäki | 166 | 1515 | 141468 |
Simon I. Hay | 165 | 557 | 153307 |
Theo Vos | 156 | 502 | 186409 |
Ali H. Mokdad | 156 | 634 | 160599 |
Steven Williams | 144 | 1375 | 86712 |
Igor Rudan | 142 | 658 | 103659 |
Mohsen Naghavi | 139 | 381 | 169048 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |
Martin McKee | 138 | 1732 | 125972 |
David A. Jackson | 136 | 1095 | 68352 |
Graham G. Giles | 136 | 1249 | 80038 |
Yang Liu | 129 | 2506 | 122380 |