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.
Papers published on a yearly basis
Papers
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TL;DR: The mechanism of action of immune checkpoint inhibitors is described, and the key clinical endocrine‐related consequences of this novel class of immunotherapies are detailed.
Abstract: Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies.
167 citations
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Royal Devon and Exeter Hospital1, University of Exeter2, University of Oxford3, Monash University, Clayton campus4, University of Cambridge5, Royal Adelaide Hospital6, Flinders University7, St. Vincent's Health System8, Royal Derby Hospital9, Liverpool Hospital10, University Hospitals Bristol NHS Foundation Trust11, University Hospital Southampton NHS Foundation Trust12, Karolinska Institutet13, University of Alberta14, University of Queensland15, Glasgow Royal Infirmary16, Örebro University17, Guy's and St Thomas' NHS Foundation Trust18, Western General Hospital19, University of Western Australia20, Queen Mary University of London21, Newcastle University22, West Middlesex University Hospital23, Imperial College Healthcare24, Royal Brisbane and Women's Hospital25, Mount Sinai Hospital, Toronto26, Norwich University27, University of Ioannina28, Groote Schuur Hospital29, University Medical Center Groningen30, University of Kiel31
TL;DR: Strong evidence of association within the class II HLA region is identified within the HLA-DQA1*02:01–HLA-DRB1*07:01 haplotype, with the most significant association identified at rs2647087, with a 9% risk of developing pancreatitis after administration of a thiopurine.
Abstract: Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
167 citations
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TL;DR: Evidence is found that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's Esophagus.
Abstract: Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
167 citations
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University of Bristol1, Great Western Hospital2, Staffordshire University3, North Tees and Hartlepool NHS Foundation Trust4, South Tees Hospitals NHS Trust5, Guy's and St Thomas' NHS Foundation Trust6, University of Manchester7, Lancashire Teaching Hospitals NHS Foundation Trust8, Cambridge University Hospitals NHS Foundation Trust9, Northumbria Healthcare NHS Foundation Trust10, Sherwood Forest Hospitals NHS Foundation Trust11, NHS Ayrshire and Arran12, Worcestershire Acute Hospitals NHS Trust13, United Hospitals14, Aintree University Hospitals NHS Foundation Trust15, Hampshire Hospitals NHS Foundation Trust16, University of Oxford17, North Bristol NHS Trust18, Sir Charles Gairdner Hospital19, University College London20
TL;DR: Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an ind welling catheter alone, with no deleterious effects.
Abstract: Background Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. Methods Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo thr...
166 citations
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University of Tasmania1, Norwegian University of Science and Technology2, Auckland University of Technology3, Royal Hobart Hospital4, St Thomas' Hospital5, Taipei Veterans General Hospital6, Imperial College London7, University College London8, National Institute for Health Research9, Aarhus University Hospital10, Shanghai Jiao Tong University11, Abbott Northwestern Hospital12, Flinders University13, Nagoya City University14, Chiba University15, University of Erlangen-Nuremberg16, Polytechnic Institute of Coimbra17, University of Perugia18, Kumamoto University19, Guy's and St Thomas' NHS Foundation Trust20, State University of New York Upstate Medical University21, Monash University22, University of Auckland23, University of North Carolina at Chapel Hill24, Tokyo Medical University25, VU University Medical Center26, University of Duisburg-Essen27, University of Tokushima28
TL;DR: Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification, indicating that stronger accuracy standards for BP devices may improve cardiovascular risk management.
166 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 |