Long-term outcomes of liver transplant recipients followed up in non-transplant centres: Care closer to home.

INTRODUCTION: Increasing rates of liver transplantation and improved outcomes have led to greater numbers of transplant recipients followed up in non-transplant centres. Our aim was to document long-term clinical outcomes of liver transplant recipients managed in this 'hub-and-spoke' healthcare model. METHODS: A retrospective analysis of all adult patients who underwent liver transplantation between 1987 and 2016, with post-transplant follow-up in two non-transplant centres in the UK (Nottingham) and Canada (Ottawa), was performed. RESULTS: The 1-, 5-, 10- and 20-year patient survival rates were 98%, 95%, 87% and 62%, and 100%, 96%, 88% and 62% in the Nottingham and Ottawa groups, respectively (p=0.87). There were no significant differences between the two centres in 1-, 5-, 10- and 20-year cumulative incidence of death-censored graft-survival (p=0.10), end-stage renal disease (p=0.29) or de novo cancer (p=0.22). Nottingham had a lower incidence of major cardiovascular events (p=0.008). CONCLUSION: Adopting a new model of healthcare provides a means of delivering post-transplant patient care close to home without compromising patient survival and long-term clinical outcomes.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

A hitherto unrecognised case of progressive multifocal leukoencephalopathy.

A 65-year-old man presented with a 6-week history of increasing confusion with associated cognitive decline. Empirical antibiotic cover for a urinary tract infection was prescribed with no response. After exhaustive radiological and pathological investigations were carried out, a diagnosis of John Cunningham virus encephalopathy was made. This case report describes the varied clinical presentation of symptoms and their management options, along with the latest clinical opinions behind them.

Clinical outcomes for cancer patients using complementary and alternative medicine.

CONTEXT: Over half of cancer patients in Singapore use some form of complementary or alternative medicine (CAM) to improve their immunity and general health status. The effectiveness of CAM, however, in reducing acute complications is currently unknown. Concerns also exist as to whether CAM may cause toxic effects in patients with cancer. OBJECTIVE: To investigate the changes in general health status, immunity, and organ function over a 6-month period in CAM and non-CAM users with cancer. DESIGN: The authors designed a single-center, retrospective cohort study. The patients had participated previously in a cross-sectional prevalence survey about the types of oral CAM they were using in addition to chemotherapy. The authors used the data from the survey and clinical and medication-use information from patients' medical and pharmaceutical records to complete the current study. SETTING: The study occurred at the National Cancer Centre Singapore (NCCS), which is the largest ambulatory cancer center in Singapore and treats two-thirds of the solid-tumor patients in Singapore. The study excluded patients if their medical records were incomplete and/or if the patients had not received any cytotoxic or targeted therapies at the time of survey. PARTICIPANTS: The authors reviewed the records of a total of 403 patients and excluded 46 patients because their records were missing (n=20) or because they had not received any form of anticancer treatment at the time of survey (n=26). They included 357 patients in the current study. The authors did not contact patients for this follow-up study. OUTCOME MEASURES: The authors collected data on clinical characteristics for each patient and assessed the differences between each characteristic at baseline (at the time of the survey) and at 6 months after baseline measurement. The authors evaluated clinical characteristics using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3. RESULTS: As a whole, CAM use provided an absolute reduction of infection episodes by 11.9% (P=.045) and of antibiotic use by 10.3% (P=.022). Subgroup analysis showed a reduction of documented infection by 17.9% (P=.02) and a 13% decrease in hospitalizations due to infections (P=.043) among metastatic cancer patients who used CAM. CAM usage was not associated with significant changes of hepatic and renal function. CONCLUSION: CAM use in patients with cancer was associated with a reduction in hospitalizations and requirements for antibiotics. CAM use was not associated with significant changes in hepatic and renal function. There is a need for well-designed, prospective clinical studies to confirm these findings.

Prognostic impact of bleomycin-induced pneumonitis on the outcome of Hodgkin's lymphoma.

Bleomycin-induced pneumonitis (BIP) has been well described in Hodgkin's lymphoma (HL) patients. The impact of BIP on patients uniformly treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) is not clear; previous studies have included patients treated with both ABVD and hybrid regimens. We reviewed our experience with BIP in HL to better understand the impact of BIP on overall survival. One hundred and eighty four consecutive patients who were treated with ABVD for newly diagnosed HL were eligible for retrospective review. BIP was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates on chest X-ray, computed tomography or presence of lung fibrosis on transbronchial lung biopsy, and the absence of infection. Patients were required to meet all three criteria to be included in the BIP group. BIP was observed in 28 patients (15%). A low albumin level and the use of colony granulocyte stimulating factor were associated with a higher risk of developing BIP. Age, smoking history, and underlying lung function were not predictive of BIP. Importantly, patients with BIP had similar rates of 5-year overall survival compared to unaffected patients. There were no deaths from BIP. Omission of bleomycin from subsequent treatment did not adversely affect the outcomes.