Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

Clinical practice guideline on pregnancy and renal disease

Abstract: Background Chronic kidney disease (CKD) is estimated to affect 3% of pregnant women in high-income countries, (Piccoli et al., 2018, #13860) which equates to between 15,000–20,000 pregnancies per year in England. The prevalence of CKD in pregnancy is predicted to rise in the future due to increasing maternal age and obesity. Although CKD is not a barrier to reproduction in most women, the risk of adverse pregnancy outcomes is increased in women with CKD including pre-eclampsia, fetal growth restriction, preterm delivery and accelerated loss of maternal renal function. CKD impacts on communication, decision-making, and the surveillance and management of women before, during, and after pregnancy. Existing guidance on the management of CKD in pregnancy includes the UK Consensus Group on Pregnancy in Renal Disease (ISBN 978–1,107,124,073) and expert review. Neither Kidney Disease Outcomes Quality Initiative (KDOQI) or National Institute of Health and Care Excellence (NICE) have produced specific guidance on the management of renal disease in pregnancy. Published guidance containing information relevant to the care of women with CKD in pregnancy includes: KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). UK Renal Association Commentary available at: BMC Nephrology 2018; 19: 240. KDOQI Clinical Practice Guideline for Haemodialysis, 2015. KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD, 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis, 2012 KDIGO Guideline for the Care of Kidney Transplant Recipients, 2009. KDIGO Clinical Practice Guidelines for Nutrition in Chronic Renal Failure, 2008. NICE: Intrapartum Care for Women with Existing Medical Conditions or Obstetric Complications and their Babies [NG121], 2019. NICE: Urinary Tract Infection (Lower) Antimicrobial Prescribing [NG109], 2018 NICE: Urinary Tract Infection (Recurrent) Antimicrobial Prescribing [NG112], 2018. NICE: Antenatal Care for Uncomplicated Pregnancies [CG62], 2008, updated 2017. NICE: Vitamin D supplement use in specific population groups [PH56], 2017 NICE: Diabetes in Pregnancy: Management from Pre-conception to the Post-partum Period [NG3], 2015. NICE: Antenatal and postnatal mental health: clinical management and service guidance [CG192], 2014, updated 2018. NICE: Fertility: Assessment and Treatment for People with Fertility Problems, 2013. NICE: Weight management before, during and after pregnancy [PH27], 2010 [additional data from 2017 surveillance available at: https://www.nice.org.uk/guidance/ph11/evidence/appendix-a-summary-of-evidence-from-surveillance-pdf-4671107966] NICE: Hypertension in Pregnancy: Diagnosis and Management [CG107], 2011 (update awaited 2019). UK Renal Association Clinical Practice Guidelines: Undernutrition in Chronic Kidney Disease, June 2019 RCOG: Thrombosis and Embolism During Pregnancy and the Puerperium, Reducing the Risk [Green-Top Guideline 37a], 2015. MBBRACE Confidential Enquiry into Maternal Deaths and Morbidity: lessons learned to inform maternity care (triennial reports) www.european-renal-best-practice.org/content/erbp-documents

Food Allergy: Update on Prevention and Tolerance

Abstract: Of the many possible hypotheses that explain the recent increase in childhood food allergy (FA), the dual-allergen exposure hypothesis has been the most extensively investigated. This chapter serves as a review and update on the prevention of FA and focuses on recently published randomized controlled trials exploring the efficacy of oral tolerance induction in infancy for the prevention of FA. As a result of these RCTs, National Institutes of Health recommendations now actively encourage the early introduction of peanut for the prevention of peanut allergy, and other countries/settings recommend the inclusion of potential common food allergens, including peanut and egg, in complementary feeding regimens commencing at approximately 6 months but not before 4 months of age. Further studies that explore the efficacy of oral tolerance induction to other common food allergens and that focus on optimal timing, duration, and adherence are required.

Infective endocarditis: A contemporary update

Abstract: Infective endocarditis (IE) remains a rare condition but one with high associated morbidity and mortality. With an ageing population and increasing use of implantable cardiac devices and heart valves, the epidemiology of IE has changed. Early clinical suspicion and a rapid diagnosis are essential to enable the correct treatment pathways to be accessed and to reduce complication and mortality rates. In the current review, we detail the latest guidelines for the evaluation and management of patients with endocarditis and its prevention.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

Abstract: Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease

Abstract: Objective: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6 , encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8 , might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN). Methods: A total of 442 probands with CMT type 2 (CMT2) (270) and dHMN (172) were screened for MT-ATP6/8 mutations after exclusion of mutations in known CMT2/dHMN genes. Mutation load was quantified using restriction endonuclease analysis. Blue-native gel electrophoresis (BN-PAGE) was performed to analyze the effects of m.9185T>C on complex V structure and function. Results: Three further probands with CMT2 harbored the m.9185T>C mutation. Some relatives had been classified as having dHMN. Patients could be separated into 4 groups according to their mutant m.9185T>C levels. BN-PAGE demonstrated both impaired assembly and reduced activity of the complex V holoenzyme. Conclusions: We have shown that m.9185T>C in MT-ATP6 causes CMT2 in 1.1% of genetically undefined cases. This has important implications for diagnosis and genetic counseling. Recognition that mutations in MT-ATP6 cause CMT2 enhances current understanding of the pathogenic basis of axonal neuropathy.