Anabolic steroid misuse is an important reversible cause of cardiomyopathy: a case report.

Background: Anabolic steroid misuse is very common and has been linked to the development of a severe cardiomyopathy, arrhythmias, and sudden death. Case summary: A 46-year-old miner presented to hospital with subacute dyspnoea and palpitations. Investigations revealed atrial fibrillation and a severe dilated cardiomyopathy with left ventricular ejection fraction of 12%. The patient had a history of longstanding exogenous testosterone administration. Haematological investigations demonstrated a marked polycythaemia, with haematocrit of 0.60 L/L (normal 0.40-0.54 L/L). Hormonal investigations revealed an elevated testosterone level of 46.4 nmol/L (normal 8.0-30.0 nmol/L) and suppressed luteinizing and follicle-stimulating hormones, consistent with excess testosterone use. The patient was referred to the endocrinology specialty team for support with ceasing excess testosterone use, while commencing guideline-directed heart failure therapy. At 6 months of follow-up, the patient's left ventricular ejection fraction had normalized and he was asymptomatic. Biochemical indicators of testosterone excess had also normalized. Discussion: Anabolic steroids are widely misused, particularly among young and middle-aged males. Cardiovascular complications include a potentially reversible severe cardiomyopathy, accelerated coronary disease, dyslipidaemia, arrhythmias, and sudden death. It is important to identify a history of anabolic steroid misuse when investigating cardiomyopathy and be alert for indicators such as polycythaemia. Cessation of anabolic steroid misuse may lead to complete reversal of cardiomyopathy but should be undertaken in close partnership with the patient and endocrinologists.

Impact of weekend admission and changes in treating team on patient flow and outcomes in adults admitted to hospital with community-acquired pneumonia.

BACKGROUND: The effect of workflow factors, such as timing of admission and changes in treating team, on patient outcomes remains inconclusive. AIMS: To investigate the impact of weekend admission and changes in treating team on four pre-defined outcomes in patients admitted to hospital with community-acquired pneumonia (CAP). METHODS: We performed an observational cohort study by utilising prospective longitudinal data collected during the IMPROVE-GAP trial, a stepped-wedge randomised study investigating an evidence-based bundle of care in the management of CAP. We assessed the effect of two exposure variables, day of admission and change of treating team, on four pre-specified outcomes: (i) length of stay; (ii) time to clinical stability; (iii) readmission within 30 days; and (iv) mortality at 30 days. Our analysis was restricted to patients with a primary diagnosis of CAP and employed multivariable Cox regression and logistic regression to adjust for potential measured confounders. RESULTS: Of 753 participants, 224 (29.7%) were admitted on the weekend and 71 (9.4%) changed treating team during admission. Weekend admissions had significantly longer hospital stays than weekday admissions (hazard ratio (95% confidence interval; P-value) 0.82 (0.70-0.98; 0.03)) and took longer to reach clinical stability (0.80 (0.68-0.95; 0.01)). Change of treating team doubled the odds of readmission at 30 days (odds ratio 1.95 (1.08-3.58; 0.03)). CONCLUSIONS: These results suggest workflow factors can negatively impact both health service and patient outcomes. Systems interventions aimed at improving out of hours service and reducing changes in treating team should be considered.

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm3 [-2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm3 [-3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm3 [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm2 [0.07 to 0.13]), p < 0.001), and total hip (0.04 g/cm2 [0.03 to 0.05], p < 0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX -176 ng/L [-275 to -76], p < 0.001; P1NP -18 mg/L [-32 to -5], p < 0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. © 2020 American Society for Bone and Mineral Research.

Persisting adverse body composition changes 2 years after cessation of androgen deprivation therapy for localised prostate cancer.

OBJECTIVE: Hypogonadism from androgen deprivation therapy (ADT) for prostate cancer causes adverse body composition changes associated with insulin resistance and decreased quality of life (QoL). Our objective was to assess whether adverse body composition changes improve after cessation of ADT. DESIGN: Prospective case-control study in a tertiary referral hospital. Thirty-four men newly commencing ADT (cases, median age: 67.6 years (interquartile range: 64.6-72.0)) and 29 age-matched (70.6 years (65.3-72.9)) prostate cancer controls not on ADT were assessed 2 years after cessation of ADT (median: 4.4 years). METHODS: Serum testosterone, body composition, handgrip strength, frailty and QoL were measured. Using a mixed model, the mean adjusted differences (MADs (95% CI)) between groups from baseline to study end are reported. RESULTS: Twenty-seven cases and 19 controls completed the study. Median duration of ADT was 2.3 years (interquartile range: 1.8-3.1). Two years after cessation of ADT, total testosterone remained lower (MAD: -3.4 nmol/L (-6.3 to -0.5), P < 0.022), fat mass (2214 g (490-3933), P = 0.025) and insulin resistance (homeostasis model assessment of insulin resistance: 0.69 (0.31-1.07), P < 0.001) remained higher in cases, whereas lean mass (-1450 g (-2259 to -640), P < 0.001) and physical component of QoL remained lower than controls (-11.9 (-16.4 to -7.4), P < 0.001). CONCLUSION: Two years after ADT cessation, metabolically adverse changes in body composition, increased insulin resistance and reduced QoL persisted. This may be related to incomplete testosterone recovery. Persisting adverse effects need to be considered in the risk to benefit assessment of ADT and proactive mitigation should continue after cessation of treatment.

A role for smoothened during murine lens and cornea development.

Various studies suggest that Hedgehog (Hh) signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci. 2012; 53, 3316-30) showed that conditionally activating Hh signals promotes murine lens epithelial cell proliferation and disrupts fibre differentiation. In this study we examined the expression of the Hh pathway and the requirement for the Smoothened gene in murine lens development. Expression of Hh pathway components in developing lens was examined by RT-PCR, immunofluorescence and in situ hybridisation. The requirement of Smo in lens development was determined by conditional loss-of-function mutations, using LeCre and MLR10 Cre transgenic mice. The phenotype of mutant mice was examined by immunofluorescence for various markers of cell cycle, lens and cornea differentiation. Hh pathway components (Ptch1, Smo, Gli2, Gli3) were detected in lens epithelium from E12.5. Gli2 was particularly localised to mitotic nuclei and, at E13.5, Gli3 exhibited a shift from cytosol to nucleus, suggesting distinct roles for these transcription factors. Conditional deletion of Smo, from ∼E12.5 (MLR10 Cre) did not affect ocular development, whereas deletion from ∼E9.5 (LeCre) resulted in lens and corneal defects from E14.5. Mutant lenses were smaller and showed normal expression of p57Kip2, c-Maf, E-cadherin and Pax6, reduced expression of FoxE3 and Ptch1 and decreased nuclear Hes1. There was normal G1-S phase but decreased G2-M phase transition at E16.5 and epithelial cell death from E14.5-E16.5. Mutant corneas were thicker due to aberrant migration of Nrp2+ cells from the extraocular mesenchyme, resulting in delayed corneal endothelial but normal epithelial differentiation. These results indicate the Hh pathway is required during a discrete period (E9.5-E12.5) in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. Defective corneal development occurs secondary to defects in lens and appears to be due to defective migration of peri-ocular Nrp2+ neural crest/mesenchymal cells.