Cumulative Cardiovascular Polypharmacy Is Associated With the Risk of Acute Kidney Injury in Elderly Patients.

Polypharmacy is common in the elderly due to multimorbidity and interventions. However, the temporal association between polypharmacy and renal outcomes is rarely addressed and recognized. We investigated the association between cardiovascular (CV) polypharmacy and the risk of acute kidney injury (AKI) in elderly patients.We used the Taiwan National Health Insurance PharmaCloud system to investigate the relationship between cumulative CV medications in the 3 months before admission and risk of AKI in the elderly at their admission to general medical wards in a single center. Community-dwelling elderly patients (>60 years) were prospectively enrolled and classified according to the number of preadmission CV medications. CV polypharmacy was defined as use of 2 or more CV medications.We enrolled 152 patients, 48% with AKI (based upon Kidney Disease Improving Global Outcomes [KDIGO] classification) and 64% with CV polypharmacy. The incidence of AKI was higher in patients taking more CV medications (0 drugs: 33%; 1 drug: 50%; 2 drugs: 57%; 3 or more drugs: 60%; P = 0.05) before admission. Patients with higher KDIGO grades also took more preadmission CV medications (P = 0.04). Multiple regression analysis showed that patients who used 1 or more CV medications before admission had increased risk of AKI at admission (1 drug: odds ratio [OR] = 1.63, P = 0.2; 2 drugs: OR = 4.74, P = 0.03; 3 or more drugs: OR = 5.92, P = 0.02), and that CV polypharmacy is associated with higher risk of AKI (OR 2.58; P = 0.02). Each additional CV medication increased the risk for AKI by 30%.We found that elderly patients taking more CV medications are associated with risk of adverse renal events. Further study to evaluate whether interventions that reduce polypharmacy could reduce the incidence of geriatric AKI is urgently needed.

Differential regulation of CHOP translation by phosphorylated eIF4E under stress conditions.

Cells respond to environmental stress by inducing translation of a subset of mRNAs important for survival or apoptosis. CHOP, a downstream transcriptional target of stress-induced ATF4, is also regulated translationally in a uORF-dependent manner under stress. Low concentration of anisomycin induces CHOP expression at both transcriptional and translational levels. To study specifically the translational aspect of CHOP expression, and further clarify the regulatory mechanisms underlying stress-induced translation initiation, we developed a CMV promoter-regulated, uORF(chop)-driven reporter platform. Here we show that anisomycin-induced CHOP expression depends on phosphorylated eIF4E/S209 and eIF2alpha/S51. Contrary to phospho-eIF2alpha/S51, phospho-eIF4E/S209 is not involved in thapsigargin-induced CHOP expression. Studies using various kinase inhibitors and mutants uncovered that both the p38MAPK-Mnk and mTOR signaling pathways contribute to stress-responsive reporter and CHOP expression. We also demonstrated that anisomycin-induced translation is tightly regulated by partner binding preference of eIF4E. Furthermore, mutating the uORF sequence abolished the anisomycin-induced association of chop mRNA with phospho-eIF4E and polysomes, thus demonstrating the significance of this cis-regulatory element in conferring on the transcript a stress-responsive translational inducibility. Strikingly, although insulin treatment activated ERK-Mnk and mTOR pathways, and consequently eIF4E/S209 phosphorylation, it failed to induce phospho-eIF2alpha/S51 and reporter translation, thus pinpointing a crucial determinant in stress-responsive translation.

Prognostic factors for pulmonary metastasectomy in hepatocellular carcinoma.

PURPOSE: To identify the prognostic factors for pulmonary metastasectomy (PM-ectomy) in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We conducted a retrospective review of patients with pulmonary metastases (PM) from HCC who had undergone curative PM-ectomy at National Taiwan University Hospital between 1990 and 2004. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify the significant prognostic factors. RESULTS: In total, 34 patients were eligible for curative PM-ectomy. The overall survival rates (Kaplan-Meier) after PM-ectomy were 65.2% and 27.5% at 2 and 5 years, respectively. High alpha-fetoprotein level, positive hepatic resection margin, and short disease-free interval (DFI) were unfavorable factors for overall survival from univariate analysis, however, only DFI (P = 0.028) was identified as an independently prognostic factor by multivariate analysis. Bilateral distribution and more PMs were unfavorable factors for PM-free survival from univariate analysis, with only PM number identified as an independent prognostic factor by multivariate analysis (P = 0.017). CONCLUSION: Patients with longer DFIs and fewer PMs can benefit from PM-ectomy in HCC.