Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Pre-discharge, but not admission, levels of NT-proBNP predict adverse prognosis following acute LVF

Abstract: Background: Circulating natriuretic peptide levels provide prognostic information following acute coronary syndromes and in chronic heart failure. Little evidence exists of their utility following hospitalisation with acute left ventricular failure (LVF). Aims: To examine the relative prognostic value of admission and pre-discharge plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) following hospitalisation with acute heart failure. Methods: NT-proBNP was measured at admission in 96 patients hospitalised with acute LVF. In a subset of 34 patients, NT-proBNP was also measured prior to discharge. Multivariate analysis was performed of the clinical and serological predictors of a combined primary endpoint of death or heart failure (hospitalisation or as an outpatient). Results: During follow up (median 350 days, range 2–762), 37 (38.5%) patients died (n=16, 16.7%), or experienced at least 1 heart failure event (n=21, 21.9%). For the entire cohort of 96 patients, only a prior history of heart failure was associated with the primary endpoint (OR 3.5 [1.10–11.08], P=0.034). Admission plasma NT-proBNP was not predictive (OR 1.84 [0.75–4.51], P=0.185). In the 34 patients for whom both admission and pre-discharge NT-proBNP was available, 19 (55.9%) died (n=8, 23.5%) or experienced heart failure (n=11, 32.4%). Only pre-discharge plasma NT-proBNP (OR 15.30 [95% CI: 1.4–168.9], P=0.026) was independently predictive of the composite endpoint. The area under the receiver–operator-characteristic (AUC ROC) curve for pre-discharge NT-proBNP was superior to that for admission NT-proBNP for prediction of death or heart failure (AUC ROC 0.87 cf 0.70), for death (0.79 cf 0.66), LVF hospitalisation (0.78 cf 0.70) or heart failure as an outpatient (0.71 cf 0.61). Conclusions: Plasma NT-proBNP measured pre-discharge provides useful prognostic information following hospitalisation with acute LVF.

An evaluation of the revised seven-point checklist for the early diagnosis of cutaneous malignant melanoma.

Abstract: The seven-point checklist has been widely advocated as a sensitive screening test for malignant melanoma. A number of groups have questioned the sensitivity of this system, especially in the detection of early lesions. We have assessed the sensitivity and specificity of the revised seven-point checklist when applied to lesions seen in our department over a 26-month period and compared it with the American ABCDE evaluation system. All melanomas (n = 65) were detected using the revised seven-point checklist and all were found to have at least one of the three major criteria defined by that system. Five (7.7%) melanomas were not picked up by the ABCDE checklist. Of 100 randomly selected patients who attended the clinic during the same period, with clinically diagnosed benign pigmented lesions, 63 had at least one major feature of the revised seven-point checklist. Forty (62%) of the melanomas, compared with only (4%) of the benign lesions, had more than one major feature. This study confirms the sensitivity of the revised seven-point checklist in the diagnosis of cutaneous malignant melanoma.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Abstract: Summary Background Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Methods We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p −8 ). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches—including functional annotation databases and gene-based and pathway-based methods—to identify pathophysiologically relevant cellular mechanisms. Findings Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10 −10 ), MSRA (rs17749155; p=5·2 × 10 −10 ), LINC00208 and BLK (rs10108511; p=2·1 × 10 −9 ), KHDRBS2 (rs62423175; p=3·0 × 10 −9 ), TPPP and CEP72 (rs9918259; p=3·2 × 10 −9 ), TMOD1 (rs7852462; p=1·5 × 10 −8 ), SATB2 (rs139606545; p=2·0 × 10 −8 ), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10 −8 ). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10 −8 ) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p −6 ) belonged to muscle cell differentiation and to mesenchyme development and differentiation. Interpretation Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. Funding US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kroner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

Abstract: Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappa B (NF kappa B) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NF kappa B, inhibitory-kappa B kinase (IKK)-gamma, IKK beta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P < 0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NF kappa B, IKK beta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NF kappa B and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue. (J Clin Endocrinol Metab 94: 261-267, 2009)

Cardiovascular responses to insertion of the laryngeal mask.

Abstract: We have compared, in 40 healthy patients, the cardiovascular responses induced by laryngoscopy and intubation with those produced by insertion of a laryngeal mask. Anaesthesia was induced with thiopentone and maintained with enflurane and nitrous oxide in oxygen; vecuronium was used for muscle relaxation. Arterial pressure was measured with a Finapres monitor. The mean maximum increase in systolic arterial pressure after laryngoscopy and tracheal intubation was 51.3% compared with 22.9% for laryngeal mask insertion (p less than 0.01). Increases in maximum heart rate were similar, (26.6% v 25.7%) although heart rate remained elevated for longer after tracheal intubation. We conclude that insertion of the laryngeal mask airway is accompanied by smaller cardiovascular responses than those after laryngoscopy and intubation and that its use may be indicated in those patients in whom a marked pressor response would be deleterious.