Institution
Glenfield Hospital
Healthcare•Leicester, United Kingdom•
About: Glenfield Hospital is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Extracorporeal membrane oxygenation. The organization has 1382 authors who have published 1812 publications receiving 99238 citations. The organization is also known as: Glenfield General Hospital.
Topics: Population, Extracorporeal membrane oxygenation, Asthma, Genome-wide association study, Lung cancer
Papers published on a yearly basis
Papers
More filters
Institute of Cancer Research1, University College London2, Francis Crick Institute3, University College London Hospitals NHS Foundation Trust4, University College Hospital5, The Royal Marsden NHS Foundation Trust6, Peter MacCallum Cancer Centre7, University of Cambridge8, University of Leicester9, Glenfield Hospital10
TL;DR: In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation, and immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.
Abstract: Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1-5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer-stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.
165 citations
Erasmus University Rotterdam1, McMaster University2, University of Washington3, Harvard University4, National Institutes of Health5, Radboud University Nijmegen6, King's College London7, University of Lausanne8, Karolinska Institutet9, VU University Amsterdam10, University of Cambridge11, Cedars-Sinai Medical Center12, University of Oxford13, University of Lübeck14, Wageningen University and Research Centre15, Glenfield Hospital16, University of Münster17, Tufts University18, University of Bergen19, Imperial College London20, University of Pennsylvania21, University of Leicester22, University of Surrey23
TL;DR: Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tH Cy concentrations and tHCy-related pathways for CAD.
159 citations
Utrecht University1, Queen Mary University of London2, University of Michigan3, McMaster University4, Case Western Reserve University5, University of North Carolina at Chapel Hill6, University of California, San Diego7, University of Pennsylvania8, University of Glasgow9, Stanford University10, Cleveland Clinic11, University of Maryland, Baltimore12, University of Oxford13, University of Wisconsin-Madison14, University of Bristol15, University of Florida16, Erasmus University Rotterdam17, Heidelberg University18, University of Groningen19, Lund University20, University of Leicester21, Glenfield Hospital22, University of Minnesota23, Columbia University24, University College London25, Tulane University26, Harvard University27, University of Cambridge28, University of Washington29, University of Dundee30, Merck & Co.31, Cedars-Sinai Medical Center32, Dalhousie University33, University College Dublin34, VU University Amsterdam35, Fred Hutchinson Cancer Research Center36, Boston University37, Imperial College London38, University of Mississippi39, Johns Hopkins University40, University of Amsterdam41, University of Texas Health Science Center at Houston42, University of London43, University of Pittsburgh44, Hannover Medical School45, University of Ulm46, Medical University of Graz47, Icahn School of Medicine at Mount Sinai48, Royal College of Surgeons in Ireland49, Brigham and Women's Hospital50
TL;DR: The findings extend the understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification and provide support for a putative role in hypertension of several genes.
Abstract: Blood pressure (BP) is a heritable risk factor for cardiovascular disease To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis We replicated findings in an independent set of 68,368 individuals of European ancestry Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2 Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules In summary, we identified previously unknown loci associated with BP Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification
158 citations
Geisinger Medical Center1, Stellenbosch University2, deCODE genetics3, Utrecht University4, University of Leicester5, Glenfield Hospital6, Pennsylvania State University7, Mayo Clinic8, Marshfield Clinic9, Polish Academy of Sciences10, Icahn School of Medicine at Mount Sinai11, Vanderbilt University12, Northwestern University13, Auckland City Hospital14, University of Washington15, Case Western Reserve University16, Group Health Cooperative17, Temple University18, Waikato Hospital19, University of Otago20, Wellcome Trust Sanger Institute21, Queen's University Belfast22, British Heart Foundation23, St George's, University of London24, Alfaisal University25, University of Leeds26, University of Western Australia27, University of Iceland28, Maastricht University29, VU University Amsterdam30, University of Groningen31, Radboud University Nijmegen32, University of Southern Denmark33, University of Cambridge34, Queensland Health35, Imperial College London36, University College London37, University of Liège38, University of Pittsburgh39, Karolinska Institutet40, Technical University of Denmark41, Uppsala University42, University of Tartu43, Wayne State University44, Paracelsus Private Medical University of Salzburg45
TL;DR: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
Abstract: RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
158 citations
TL;DR: The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy.
Abstract: The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 – 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation).
158 citations
Authors
Showing all 1385 results
| Name | H-index | Papers | Citations |
|---|---|---|---|
| Nilesh J. Samani | 149 | 779 | 113545 |
| Daniel I. Chasman | 134 | 484 | 72180 |
| Massimo Mangino | 116 | 369 | 84902 |
| Ian D. Pavord | 108 | 575 | 47691 |
| Christopher E. Brightling | 103 | 552 | 44358 |
| Ulf Gyllensten | 100 | 368 | 59219 |
| Pim van der Harst | 99 | 517 | 42777 |
| Andrew J. Wardlaw | 92 | 311 | 33721 |
| Kenneth J. O'Byrne | 87 | 629 | 39193 |
| Paul Burton | 85 | 418 | 42766 |
| Bryan Williams | 82 | 454 | 40798 |
| Marylyn D. Ritchie | 80 | 459 | 32559 |
| John R. Thompson | 78 | 202 | 50475 |
| Maria G. Belvisi | 73 | 269 | 16021 |
| Martin D. Tobin | 72 | 218 | 34028 |