Thiazide use and skeletal microstructure: Results from a multi-ethnic study.

Background: Thiazide diuretics, a commonly used class of anti-hypertensives, have been associated with increased areal bone mineral density (aBMD). Data regarding effects on fracture are conflicting and no information is available regarding effects on skeletal microstructure and mechanical competence. Methods: We compared skeletal microstructure, volumetric BMD (vBMD), stiffness and prevalent fractures in current thiazide diuretic users and non-users from a population-based multiethnic cohort of elderly adults age ≥ 65 years (N = 599) with high resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis. Results: Female current thiazide diuretic users had higher weight and BMI and were more likely to be non-Caucasian compared to non-users. There were no differences in age, historical fractures or falls between female users and non-users. Female thiazide users tended to have lower calcium and vitamin d intake compared to non-users. After adjusting for age, weight, race and other covariates, 1/3-radius mean aBMD by dual energy x-ray absorptiometry (DXA) was 3.2% (p = 0.03) higher in female users vs. non-users. By HRpQCT, adjusted mean cortical vBMD was 2.4% (p = 0.03) higher at the radius in female users vs. non-users, but there was no difference in stiffness. DXA results were similar in the subset of Black females. There was no difference in any adjusted aBMD or cortical skeletal parameters by DXA or HRpQCT respectively in males. Conclusions: Thiazide use was associated with a modestly higher aBMD at the predominantly cortical 1/3-radius site and radial cortical vBMD by HRpQCT in females. The effect on cortical bone may offer skeletal benefits in women taking thiazides for other indications such as hypertension, hypercalciuria or recurrent nephrolithiasis.

Coronavirus disease 2019, vitamin D and kidney function.

PURPOSE OF REVIEW: The purpose of this review is to summarize the emerging studies analyzing the association between vitamin D and risk of COVID-19 infection and severity, as well as the early interventional studies investigating the protective effect of vitamin D supplementation against COVID-19. RECENT FINDINGS: Studies investigating the association between vitamin D levels and risk of COVID-19 infection and risk of severe disease and mortality among those infected have yielded mixed results. Thus far, the majority of studies investigating the association between vitamin D and COVID-19 have been observational and rely on vitamin D levels obtained at the time of admission, limiting causal inference. Currently, clinical trials assessing the effects of vitamin D supplementation in individuals with COVID-19 infection are extremely limited. Randomized, interventional trials may offer more clarity on the protective effects of vitamin D against COVID-19 infection and outcomes. SUMMARY: Decreased levels of vitamin D may amplify the inflammatory effects of COVID-19 infection, yet, data regarding the mortality benefits of vitamin D supplementation in COVID-19-infected individuals are still limited. Current observational data provides the impetus for future studies to including randomized controlled trials to determine whether vitamin D supplementation in COVID-19-infected individuals with kidney disease can improve mortality outcomes.

Corynebacterium Striatum Bacteremia in End-Stage Renal Disease: A Case Series and Review of Literature.

Corynebacterium striatum is emerging as an opportunistic pathogen in immunocompromised hosts. End-stage renal disease remains an underappreciated state of immunocompromise. We present a series of individuals with end-stage kidney disease on hemodialysis who developed Corynebacterium striatum bacteremia, which was initially thought to be a contaminant, but eventually recognized as the culprit pathogen. We review the bacteriology of C. striatum, increasing resistance, as well as known cases of C. striatum bacteremia in the setting of end-stage renal disease. These cases highlight the importance of a high index of suspicion when interpreting bacterial cultures in patients with end-stage renal disease.

Enteric neurons synthesize netrins and are essential for the development of the vagal sensory innervation of the fetal gut.

During fetal life, vagal sensory fibers establish a reproducible distribution in the gut that includes an association with myenteric ganglia. Previous work has shown that netrin is expressed in the bowel wall and, by acting on its receptor, deleted in colorectal cancer (DCC), mediates the guidance of vagal sensory axons to the developing gut. Because the highest concentration of netrins in fetal bowel is in the endoderm, we tested the hypothesis that the ingrowth of vagal afferents to the gut would be independent of the presence of enteric neurons, although enteric neurons might influence the internal distribution of these fibers. Surprisingly, experiments indicated that the vagal sensory innervation is intrinsic neuron-dependent. To examine the vagal innervation in the absence of enteric ganglia, fetal Ret -/- mice were labeled by applying DiI bilaterally to nodose ganglia. In Ret -/- mice, DiI-labeled vagal sensory axons descended in paraesophageal trunks as far as the proximal stomach, which contains neurons, but did not enter the aganglionic bowel. To determine whether neurons produce netrins, enteric neural-crest-derived cells (ENCDCs) were immunoselected from E15 rat gut. Transcripts encoding netrin-1 and -3 were not detected in the ENCDCs, but appeared after they had given rise to neurons. When these neurons were cocultured with cells expressing c-Myc-tagged netrin-1, the neurons displayed netrin-1, but not c-Myc, immunoreactivity. Enteric neurons thus synthesize netrins. The extent to which neuronal netrin accounts for the dependence of the vagal sensory innervation on intrinsic neurons, remains to be determined.