John Radcliffe Hospital

About: John Radcliffe Hospital is a healthcare organization based out in Oxford, Oxfordshire, United Kingdom. It is known for research contribution in the topics: Population & Antigen. The organization has 14491 authors who have published 23670 publications receiving 1459015 citations.

A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer.

Abstract: Background: The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior. Methods: A national database, collated prospectively from 21 regional centres, detailed TEM treatment in 487 subjects with rectal cancer. Data were used to construct a predictive model of local recurrence after TEM using semiparametric survival analyses. The model was internally validated using measures of calibration and discrimination. Results: Postoperative morbidity and mortality were 14·9 and 1·4 per cent respectively. The Cox regression model predicted local recurrence with a concordance index of 0·76 using age, depth of tumour invasion, tumour diameter, presence of lymphovascular invasion, poor differentiation and conversion to radical surgery after histopathological examination of the TEM specimen. Conclusion: Patient selection for TEM is frequently governed by fitness for radical surgery rather than suitable tumour biology. TEM can produce long-term outcomes similar to those published for radical total mesorectal excision surgery if applied to a select group of biologically favourable tumours. Conversion to radical surgery based on adverse TEM histopathology appears safe for p T1 and p T2 lesions.

Native T1 mapping in transthyretin amyloidosis

Abstract: Objectives The aims of the study were to explore the ability of native myocardial T1 mapping by cardiac magnetic resonance to: 1) detect cardiac involvement in patients with transthyretin amyloidosis (ATTR amyloidosis); 2) track the cardiac amyloid burden; and 3) detect early disease. Background ATTR amyloidosis is an underdiagnosed cause of heart failure, with no truly quantitative test. In cardiac immunoglobulin light-chain amyloidosis (AL amyloidosis), T1 has high diagnostic accuracy and tracks disease. Here, the diagnostic role of native T1 mapping in the other key type of cardiac amyloid, ATTR amyloidosis, is assessed. Methods A total of 3 groups were studied: ATTR amyloid patients (n = 85; 70 males, age 73 ± 10 years); healthy individuals with transthyretin mutations in whom standard cardiac investigations were normal (n = 8; 3 males, age 47 ± 6 years); and AL amyloid patients (n = 79; 55 males, age 62 ± 10 years). These were compared with 52 healthy volunteers and 46 patients with hypertrophic cardiomyopathy (HCM). All underwent T1 mapping (shortened modified look-locker inversion recovery); ATTR patients and mutation carriers also underwent cardiac 3,3-diphosphono-1,2-propanodicarboxylicacid (DPD) scintigraphy. Results T1 was elevated in ATTR patients compared with HCM and normal subjects (1,097 ± 43 ms vs. 1,026 ± 64 ms vs. 967 ± 34 ms, respectively; both p Conclusions Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloid, but with lower maximal T1 elevation, and appears to be an early disease marker.

TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

Abstract: Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS), it has been difficult to demonstrate which variants are causal and what role they have in disease. Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation.