The Queen Elizabeth Hospital Charity exists to support medical and health research, and to encourage excellence in healthcare for patients and their care givers, wholly or mainly through the services provided by University Hospital Birmingham NHS Foundation Trust. It raises money for campaigns that are over and above what the NHS can provide. QEH Charity was formed in 2001, however there has been an official charity associated with the Queen Elizabeth Hospital since the creation of the NHS in 1948. The charity will become independent in April 2016..
Background:Major adverse cardiovascular events (MACE) are common early after liver transplantation (LT) as reported in the United States, but incidence is not well described in a European cohort. With lower MACE rates reported after kidney transplantation in the United Kingdom versus the United States, it is important to determine if a similar incongruity exists after LT. Methods:In this large retrospective, population cohort study, we studied all LT procedures performed in England between 1st April 2002 and 31st March 2023 (n = 10,213). MACE data was obtained from Hospital Episode Statistics, an administration data warehouse for any hospitalization to English NHS hospital, and defined as any of the following: myocardial infarction, stroke, unstable angina, heart failure, any coronary revascularization procedure and any cardiovascular-defined death. Findings:MACE-related 1-year mortality was low at 0.1% (n = 11). Overall, MACE occurred in 268 (2.6%) LT recipients within the first year after LT, of which 125 (1.2%) occurred within the first month. The commonest observed MACE was stroke (n = 129, 1.3%), followed by myocardial infarction (n = 89, 0.9%). After adjustment, MACE within the first year was associated with increased risk for long-term all-cause mortality (Hazard Ratio 1.37, 95% CI 1.05-1.79, p = 0.021). In a competing risk regression model, with non-cardiac death a competing risk, the following were independently associated with increased risk of MACE after LT: increasing age, male sex, diabetes, and higher Charlson co-morbidity score. Interpretation:MACE and cardiovascular death are uncommon within the first-year post LT in England. However, liver transplant recipients with non-fatal MACE have inferior long-term survival. Further work is warranted to determine the best strategy to mitigate cardiac risk stratification for LT candidates and evidence-based strategies to mitigate cardiovascular risk after LT must be encouraged. Funding:Nothing to disclose.
Background We conducted a single-arm interventional study, to explore mucosal changes associated with clinical remission under oral vancomycin (OV) treatment, in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD); NCT05376228.Methods Fifteen patients with PSC and active colitis (median fecal calprotectin 459 mu g/g; median total Mayo score 5) were treated with OV (125 mg QID) for 4 weeks and followed-up for a further 4 weeks of treatment withdrawal (8 weeks, end-of-study). Colonic biopsies were obtained at baseline and Week 4. Clinical assessments, and serum and stool samples (metagenomics, metatranscriptomics, and metabolomics) were collected at Weeks 0, 2, 4, and 8. The primary efficacy outcome measure was the induction of clinical remission.Results Oral vancomycin resulted in clinical remission in 12/15 patients and significant reductions in fecal calprotectin. Oral vancomycin was associated with reduced abundances of Lachnospiraceae, genera Blautia and Bacteroides; and enrichment of Enterobacteriaceae, and genera Veillonella, Akkermansia, and Escherichia. Oral vancomycin treatment was associated with the downregulation of multiple metatranscriptomic pathways (including short-chain fatty acid [SCFA] metabolism and bile acid [BA] biotransformation), along with host genes and multiple pathways involved in inflammatory responses and antimicrobial defence; and an upregulation of genes associated with extracellular matrix repair. Oral vancomycin use resulted in the loss of specific fecal SCFAs and secondary BAs, including lithocholic acid derivatives. Colitis activity relapsed following OV withdrawal, with host mucosal and microbial changes trending toward baseline.Conclusions Four weeks of OV induces remission in PSC-IBD activity, associated with a reduction in gut bacterial diversity and compositional changes relating to BA and SCFA homeostasis.
BACKGROUND:Bronchiectasis guidelines are inconsistent with regard to the effectiveness of mucoactive agents, and their use varies geographically. Large trials are needed to assess safety and effectiveness. METHODS:For this open-label, randomized, two-by-two factorial trial at 20 sites in the United Kingdom, we enrolled participants with non-cystic fibrosis bronchiectasis who had frequent pulmonary exacerbations and daily sputum production. Current smokers and persons who had recently received mucoactive treatments were excluded. All participants received standard care and were also assigned either to one of three mucoactive-drug groups - hypertonic saline (the hypertonic-saline group), hypertonic saline and carbocisteine (the combination group), or carbocisteine (the carbocisteine group) - or to standard care alone. The comparisons were between hypertonic saline and no hypertonic saline and between carbocisteine and no carbocisteine, with each category consisting of two groups. The primary outcome was the number of pulmonary exacerbations over a 52-week period. Key secondary outcomes were scores on disease-specific health-related quality-of-life assessments, time to next pulmonary exacerbation, and safety. RESULTS:A total of 288 participants underwent randomization. No treatment interactions were found. The mean number of adjudicated fully qualifying pulmonary exacerbations over the 52-week period was 0.76 (95% confidence interval [CI], 0.58 to 0.95) with hypertonic saline as compared with 0.98 (95% CI, 0.78 to 1.19) with no hypertonic saline (adjusted between-group difference in the means, -0.25 [95% CI, -0.57 to 0.07; P = 0.12]) and 0.86 (95% CI, 0.66 to 1.06) with carbocisteine as compared with 0.90 (95% CI, 0.70 to 1.09) with no carbocisteine (adjusted between-group difference in the means, -0.04 [95% CI, -0.36 to 0.28; P = 0.81]). Secondary outcomes and the incidence of adverse events, including serious adverse events, were similar across the groups. CONCLUSIONS:In participants with bronchiectasis, neither hypertonic saline nor carbocisteine significantly reduced the mean incidence of pulmonary exacerbations over a period of 52 weeks. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme and others; ISRCTN Registry number, ISRCTN89040295.).
