Royal Devon and Exeter Hospital

About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.

How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum

Abstract: MLL2 mutations are detected in 55 to 80% of patients with Kabuki syndrome (KS) In 20 to 45% patients with KS, the genetic basis remains unknown, suggesting possible genetic heterogeneity Here, we present the largest yet reported cohort of 116 patients with KS We identified MLL2 variants in 74 patients, of which 47 are novel and a majority are truncating We show that pathogenic missense mutations were commonly located in exon 48 We undertook a systematic facial KS morphology study of patients with KS at our regional dysmorphology meeting Our data suggest that nearly all patients with typical KS facial features have pathogenic MLL2 mutations, although KS can be phenotypically variable Furthermore, we show that MLL2 mutation-positive KS patients are more likely to have feeding problems, kidney anomalies, early breast bud development, joint dislocations and palatal malformations in comparison with MLL2 mutation-negative patients Our work expands the mutation spectrum of MLL2 that may help in better understanding of this molecule, which is important in gene expression, epigenetic control of active chromatin states, embryonic development and cancer Our analyses of the phenotype indicates that MLL2 mutation-positive and -negative patients differ systematically, and genetic heterogeneity of KS is not as extensive as previously suggested Moreover, phenotypic variability of KS suggests that MLL2 testing should be considered even in atypical patients

Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment.

Abstract: OBJECTIVE--To determine the age related incidence of advanced chronic renal failure in two areas of England. DESIGN--Prospective study of patients newly identified as having advanced chronic renal failure within a two year period; subsequent monitoring of patients' clinical course for a further 26 months. SETTING--Devon and Blackburn. SUBJECTS--Those patients in a population of 708,997 who developed advanced chronic renal failure (serum creatinine concentration greater than 500 mumol/l) for the first time during a two year period. MAIN OUTCOME MEASURES AND RESULTS--210 Patients (148 per million population per year) developed advanced chronic renal failure, 117 (51%) of whom were over 70. The age related incidence rose from 58 per million per year in those aged 20-49 to 588 per million per year in those aged 80 or over. Only 54% (113) of patients were referred to a nephrologist; 120 patients (57%) needed dialysis or died within three months of presenting without receiving dialysis, and 187 (89%) died or needed dialysis within three years. After those unsuitable for further treatment had been excluded, 78 patients per million population per year aged under 80 needed to start long term renal replacement treatment. CONCLUSIONS--Many patients suitable for renal replacement treatment are still not referred for nephrological opinion and are denied treatment. If the treatment rate in the United Kingdom rose from the 1988 rate of 55.1 per million per year to 78 per million per year then the number of patients receiving treatment would rise to about 800 per million. This is double the present number and has considerable but predictable resource implications for the NHS.

A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management?

Abstract: Aim The aim of the study was to assess the outcome of patients who received chemoradiotherapy (CRT) for locally advanced rectal cancer, specifically those with complete clinical response (CCR) and who were then managed nonoperatively with a ‘Watch and Wait’ follow-up protocol. Method A retrospective study was carried out of patients undergoing preoperative CRT for rectal cancer, conducted in a district general hospital managing rectal cancer through the multidisciplinary team process. Results Forty-nine patients received preoperative CRT over a 5-year period (2004–2009). Twelve (24%) were considered potentially to have had a complete response on MRI. Of these, six subsequently had clinical evidence of residual disease, leading to surgery (mean time to surgery, 24 weeks; range, 12–36 weeks). The remaining six had CCR, avoiding surgery (mean follow up, 26 months; range, 12–45 months), with all six patients disease free to date. A further six patients had complete pathological response (CPR) following surgery after comprehensive histopathological assessment of the specimen. Conclusion In this consecutive series of patients with locally advanced rectal cancer treated with CRT, 12% demonstrated a CCR and have been actively managed conservatively, thereby avoiding surgery. With further improvements in diagnostic assessment of response to CRT, this figure may rise.

Exacerbation frequency and course of COPD

Abstract: Background Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.