Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.

Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.

Survival and analysis of predictors of mortality in patients undergoing replacement renal therapy: a 20-year cohort.

BACKGROUND: optimal management of end-stage renal disease (ESRD) in hemodialysis (HD) patients should be more studied because it is a serious risk factor for mortality, being considered an unquestionable global priority. METHODS: we performed a retrospective cohort study from the Nephrology Service in Brazil evaluating the survival of patients with ESRD in HD during 20 years. Kaplan-Meier method with the Log-Rank and Cox's proportional hazards model explored the association between survival time and demographic factors, quality of treatment and laboratory values. RESULTS: Data from 422 patients were included. The mean survival time was 6.79 ± 0.37. The overall survival rates at first year was 82,3%. The survival time correlated significantly with clinical prognostic factors. Prognostic analyses with the Cox proportional hazards regression model and Kaplan-Meier survival curves further identified that leukocyte count (HR = 2.665, 95% CI: 1.39-5.12), serum iron (HR = 8.396, 95% CI: 2.02-34.96), serum calcium (HR = 4.102, 95% CI: 1.35-12.46) and serum protein (HR = 4.630, 95% CI: 2.07-10.34) as an independent risk factor for the prognosis of survival time, while patients with chronic obstructive pyelonephritis (HR = 0.085, 95% CI: 0.01-0.74), high ferritin values (HR = 0.392, 95% CI: 0.19-0.80), serum phosphorus (HR = 0.290, 95% CI: 0.19-0.61) and serum albumin (HR = 0.230, 95% CI: 0.10-0.54) were less risk to die. CONCLUSION: survival remains low in the early years of ESRD treatment. The present study identified that elevated values of ferritin, serum calcium, phosphorus, albumin, leukocyte, serum protein and serum iron values as a useful prognostic factor for the survival time.