BackgroundAlthough the optimal timing of initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury has been extensively studied in the past, it is still unclear.MethodsIn this systematic review, we searched all related randomized controlled trials (RCTs) that directly compared earlier and later RRT published prior to June 25, 2016, from PubMed, MEDLINE, and EMBASE. We extracted the study characteristics and outcomes of all-cause mortality, RRT dependence, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsWe identified 51 published relevant studies from 13,468 screened abstracts. Nine RCTs with 1627 participants were included in this meta-analysis. Earlier RRT was not associated with benefits in terms of mortality [relative risk (RR) 0.88, 95% confidence interval (CI) 0.68–1.14, p = 0.33] and RRT dependence (RR 0.81, 95% CI 0.46–1.42, p = 0.46). There were also no significant differences in the ICU and hospital LOS between patients who underwent earlier versus later RRT [standard means difference −0.08 (95% CI −0.26 to 0.09) and −0.11 (95% CI −0.37 to 0.16) day, respectively]. In subgroup analysis, earlier RRT was associated with a reduction in the in-hospital mortality among surgical patients (RR 0.78, 95% CI 0.64–0.96) and patients who underwent continuous renal replacement therapy (CRRT) (RR 0.80, 95% CI 0.67–0.96).ConclusionsCompared with later RRT, earlier initiation of RRT did not show beneficial impacts on patient outcomes. However, a lower rate of death was observed among surgical patients and in those who underwent CRRT. The included literature is highly heterogeneous and, therefore, potentially subject to bias. Further high-quality RCT studies are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0265-6) contains supplementary material, which is available to authorized users.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Although statin treatment is recommended for patients with chronic kidney disease (CKD) stages I–IV, its potential benefits have not been reported in advanced CKD patients. Non-diabetic patients with advanced CKD (pre-dialysis patients, estimated glomerular filtration rate <15 mL/min/1.73 m2) were enrolled from a National Health Insurance Research Database with a population of 23 million. Statin users and non-users were matched using propensity scoring and analyzed using Cox proportional hazards models, taking mortality as a competing risk with subsequent end-stage renal disease (ESRD) and statin doses as time-dependent variables. A total of 2551 statin users and 7653 matched statin non-users were identified from a total 14,452 patients with advanced CKD. Taking mortality as a competing risk, statin use did not increase the risk of new-onset diabetes mellitus (NODM) or decrease the risk of de novo major adverse cardiovascular events (MACE), but reduced all-cause mortality (hazard ratio (HR) = 0.59 [95% CI 0.42–0.84], p = 0.004) and sepsis-related mortality (HR = 0.53 [95% CI 0.32–0.87], p = 0.012). For advanced CKD patients, statin was neither associated with increased risks of developing NODM, nor with decreased risk of de novo MACE occurrence, but with a reduced risk of all-cause mortality, mainly septic deaths.

Due to high prevalence and mortality and the lack of effective therapies, prostate cancer is one of the most crucial health problems in men. Drug resistance aggravates the situation, not only in human prostate cancer but also in other cancers. In this study, we report for the first time that cardiac glycosides (e.g. ouabain and digitoxin) induced resistance of human prostate cancer cells (PC-3) in vitro to tubulin-binding anticancer drugs, such as paclitaxel, colchicine, vincristine and vinblastine. Cardiac glycosides exhibited amazing ability to reverse the G2/M arrest of the cell cycle and cell apoptosis induced by tubulin-binding agents. However, neither ionomycin (a Ca²⁺ ionophore) nor veratridine (a Na⁺ ionophore) mimicked the preventive action of cardiac glycosides, indicating that elevation of the intracellular Ca²⁺ concentration and Na⁺ accumulation were not involved in the cardiac glycoside action. Furthermore, cardiac glycosides showed little influence on the effects induced by actinomycin D, anisomycin and doxorubicin, suggesting selectivity for microtubule-targeted anticancer drugs. Using in situ immunofluorescent detection of mitotic spindles, our data showed that cardiac glycosides diminished paclitaxel-induced accumulation of microtubule spindles; however, in a non-cell assay system, cardiac glycosides had little influence on colchicine- and paclitaxel-induced microtubule dynamics. Using an isotope-labeled assay method, we found that ouabain modestly but significantly inhibited the transport of [¹⁴C]paclitaxel from the cytosol into the nucleus. It is suggested that cardiac glycosides inhibit the G2/M arrest induced by tubulin-binding anticancer drugs via an indirect blockade on microtubule function. The decline in transport of these drugs into the nucleus may partly explain the action of cardiac glycosides.

The purpose of this study was to compare the accuracy of pretransplant test-dose pharmacokinetic (PK) profiling after administration of the microemulsion (CsA-ME; Neoral) versus the corn oil-based (CsA-GC; Sandimmune) gel capsule formulations of cyclosporin A (CsA) to estimate posttransplant CsA bioavailability and to individualize starting drug doses. The absolute oral bioavailability (F), clearance rate (CL), average blood concentration (C[av]), peak concentration (Cmax), and time to Cmax (tmax) values were calculated from paired intravenous and oral pretransplant PK profiles of renal transplant candidates, using CsA-GC (n = 70) or CsA-ME (n = 70) administration. The initial posttransplant oral CsA dose was estimated by linear extrapolation of the observed pretransplant value to the target concentration. Because higher mean F (P < 0.0001), but not CL, values were observed in end-stage renal disease patients after CsA-ME compared with CsA-GC treatment, the predicted starting doses for each therapy were markedly different (P < 0.01). From posttransplant days 5 to 7, 54% of patients treated with CsA-ME had a mean dose-normalized C(av) (C(av)/dose, D) value within 20% of the target concentration, compared with 42% of patients treated with CsA-GC (P = 0.03). Administration of the predicted oral dose of CsA-ME produced a Cmax > 700 ng/ml in 90% of patients from days 2 to 4, and in 97% from days 5 to 7, whereas administration of the predicted oral dose of CsA-GC produced a Cmax > 700 ng/ml in only 64 and 82% of patients during these same time periods, respectively (both P < 0.05). The mean estimated posttransplant F value of CsA-ME was significantly higher than that of CsA-GC; even at postoperative day 5 the value for CsA-GC was significantly lower than the pretransplant estimate (P < 0.01). Therefore, CsA-ME pretransplant PK profiles yield more accurate predictions for appropriate starting drug doses than those of CsA-GC.

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We report an unusual case of simultaneous ureteroiliac fistula and common iliac artery occlusion, managed with an endovascular approach. A 69-year-old woman with ureteral transition cell carcinoma, who had a double J tube insertion for her left hydroureter for years, developed sudden onset of massive hematuria. CT scan showed a left common iliac artery-ureteric fistula and right common iliac artery occlusion. This was successfully treated with covered stents.

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