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.

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes

Abstract: Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.

A review of 202 periprosthetic fractures--stem revision and allograft improves outcome for type B fractures

Abstract: We report a retrospective review of the outcome of treatment of 202 periprosthetic fractures around total hip arthroplasty (THA) from two specialised arthroplasty centres. Fractures were classified according to the Vancouver classification. The aim was to evaluate treatment methods with respect to stem revision and grafting. Transverse B1 fractures treated with stem revision compared to those treated with open reduction and internal fixation (ORIF) with a plate showed a trend towards improved overall union rate (OR=2, p=0.6, 95% CI:0.14-28.4) and shorter times to union (p=0.038, mean 12 months SD 6.573 for ORIF versus 4.48 months SD 0.757 for stem revision). B2 fractures undergoing stem revision and grafting were significantly more likely to unite compared to ORIF alone (OR=17.3, p=0.018 95%CI:1.63-184.4). B3 fractures presented with significant variation in fracture configuration and bone loss and therefore their treatment was individualised. When treated with stem revision and grafting healing was achieved in a mean time of 7 months (n=81). Periprosthetic fractures of the femur are highly complex and challenging. Stem revision for transverse B1 fractures is now considered as a viable treatment modality as this fracture configuration is difficult to control with single plating, and fixation with a long stem bypassing the distal fracture line is necessary to achieve axial stability and healing. Bone allografting, whether used as a cortical onlay or in morselised impacted form for B2 and B3 fractures enhances fracture healing.

Multifunctional redox catalysts as selective enhancers of oxidative stress

Abstract: Certain cancer cells proliferate under conditions of oxidative stress (OS) and might therefore be selectively targeted by redox catalysts. Among these catalysts, compounds containing a chalcogen and a quinone redox centre are particularly well suited to respond to the presence of OS. These catalysts combine the specific electrochemical features of quinones and chalcogens. They exhibit high selectivity and efficiency against oxidatively stressed rat PC12, human Jurkat and human Daudi cells in cell culture, where their mode of action most likely involves the catalytic activation of existent and the generation of new reactive oxygen species. The high efficiency and selectivity shown by these catalysts makes them interesting for the development of anti-cancer drugs.

Malignant Lymphoma of the Lower Urinary Tract: A Clinicopathological Study with Review of the Literature

Abstract: Summary— The clinical and histopathological findings are reported in 3 primary malignant lymphomas of the lower urinary tract. Two arose in the bladders of a 70-year-old man and a 67-year-old woman. The first was histologically low grade and the patient remains free of disease after more than 7 years. The second was an intermediate grade neoplasm and the patient died after 39 months. The third tumour was found in the urethra of a 76-year-old woman and it appears to represent only the third primary malignant lymphoma described at this site. The bladder is an uncommon primary site of extranodal lymphoma. Most patients present with haematuria and cystoscopy shows 1 or more solid, round, tumour-like masses. Histological grade, particularly follicle formation, appears to have predictive value.