Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis

AbstractBackgroundTestosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA).MethodsSingle-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal.ResultsMean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass.ConclusionHypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis

Loss of function SETD2 mutations in poorly differentiated metastases from two Hürthle cell carcinomas of the thyroid

Hürthle cell carcinomas (HCC) are rare differentiated thyroid cancers that display low avidity for radioactive iodine and respond poorly to kinase inhibitors. Here, using next-generation sequencing, we analyzed the mutational status of primary tissue and poorly differentiated metastatic tissue from two HCC patients. In both cases, metastatic tissues harbored a mutation of SETD2, each resulting in loss of the SRI and WW domains of SETD2, a methyltransferase that trimethylates H3K36 (H3K36me3) and also interacts with p53 to promote its stability. Functional studies of the novel p.D1890fs6* mutation (case 1) revealed significantly reduced H3K36me3 levels in SETD2-mutated tissue and primary cell cultures and decreased levels of the active form of p53. Restoration of SETD2-wildtype expression in the SETD2-mutant cells significantly reduced the expression of four well-known stemness markers (OCT-4, SOX2, IPF1, Goosecoid). These findings suggest potential roles for SETD2 loss-of-function mutations in HCC progression, possibly involving p53 destabilization and promotion of stemness. Their prevalence and potential treatment implications in thyroid cancer, especially HCC, require further study

β2-Adrenergic receptor stimulation improves endothelial progenitor cell-mediated ischemic neoangiogenesis

Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. β2-Adrenergic receptor (β2AR) plays a critical role in vascular tone regulation and neoangiogenesis

Body Composition Changes in Hemodialysis Patients: Implications for Prognosis

Background: Overhydration, inflammation and protein-energy wasting have been related to all-cause mortality in dialysis patients, being lean mass loss, a poor prognostic factor. Objective: to monitor body composition changes (BCC) in hemodialysis (HD) patients and to relate BCC to mortality. Methods: Prospective follow up study: Bioimpedance spectroscopy (BIS) and nutritional parameters were performed every 6 months during three years. Results : Overall data show a significant loss of weight at 12m, 24m, and 36m, with decrease of lean tissue index and phase angle (PA) in each period measured. Fat tissue index (FTI) diminished in the third year’s measurements. End of first year, 41 % of patients gain weight, them at baseline had lower age, higher serum albumin, lower Extracelular/intracellular water index (ECW/ICW) and higher PA, showing a significant FTI increase. Higher baseline PA was gain weight predictor by binary logistic regression. Cox regression analyses: Age, diabetes, HD technique, albumin, ECW/ICW, and PA were mortality predictors in univariate analysis; being PA the main mortality predictor in multivariate analysis. BCC were not associated with mortality. ROC curve: PA higher than 4.85° is protective for mortality. Conclusions: Lean mass loss was the most important change during follow up; we have not observed association between BCC with mortality. PA was the main mortality predictor.S

Echocardiographic findings in haemodialysis patients according to their state of hydration

AbstractBackgroundChronic fluid overload is frequent in hemodialysis patients (P) and it associates with hypertension, left ventricular hypertrophy (LVH) and higher mortality. Moreover, echocardiographic data assessing fluid overload is limited. Our aim was to evaluate the relationship between fluid overload measured by bioimpedance spectroscopy (BIS) and different echocardiographic parameters.MethodsCross-sectional observational study including 76 stable patients. Dry weight was clinically assessed. BIS and echocardiography were performed. Weekly time-averaged fluid overload (TAFO) and relative fluid overload (FO/ECW) were calculated using BIS measurements.ResultsBased on TAFO three groups were defined: A- dehydrated, TAFO <-0.25 L 32 P (42%); B- normohydrated, TAFO between -0.25 and 1.5 l: 26 (34%); C- overhydrated, TAFO>1.5 l: 18 (24%). We found significant correlation between TAFO and left atrial volume index (LAVI) (r: 0.29; p=0.013) but not with FO/ECW (r 0.06; p=0.61). TAFO, but not FO/ECW kept a significant relationship with LAVI (p=0.03) using One-Way ANOVA test and linear regression methods. LVH was present in 73.7% (concentric 63.2%, eccentric in 10.5%). No differences between groups in the presence of LVH or left ventricular mass index were found.ConclusionsWe found that left atrial volume index determined by echocardiographic Area-length method, but not left ventricle hypertrophy or dimensions of cavities, are related on hydration status based on bioimpedance measured time-averaged fluid overload (TAFO), and not with FO/ECW

What are the Red flags to aid the early detection of metastatic bone disease as a cause of back pain?

Existing high performance work system (HPWS) research has rarely considered cultural influences. This study investigates the relationships between guanxi, HPWS and employee attitudes in China. A data set consisting of 226 employees in a Chinese state-owned enterprise in the railway sector was used to test the hypotheses. Using structural equation modelling as an analytical tool, we found that guanxi was positively related to HPWS and trust. Similar to research in the Western context, HPWS was found to be positively related to trust and job satisfaction. Moreover, the results also revealed that HPWS mediated between guanxi and both trust and job satisfaction. Theoretical and practical implications are both discussed

Adipokines and coronary artery disease

Adipose tissue, besides being an important energetic storage, is also a source of cytokines and hormones which act in a paracrine, autocrine and especially endocrine manner, influencing the cardiometabolic axis. Adipokines are a group of mediators with pleiotropic function, that are involved in many physiological processes, so that a disregulation in their secretion can lead to multiple pathological conditions. In this review our aim was to clarify the role of adipokines in the pathogenesis of atherosclerosis, especially in coronary artery disease, and based on current scientific evidence, to analyze the therapeutic and behavioral strategies that are so far available