Resveratrol alleviates the cytotoxicity induced by the radiocontrast agent, ioxitalamate, by reducing the production of reactive oxygen species in HK-2 human renal proximal tubule epithelial cells in vitro.

Radiocontrast-induced nephropathy (RIN) is one of the leading causes of hospital-acquired acute kidney injury (AKI). The clinical strategies currently available for the prevention of RIN are insufficient. In this study, we aimed to determine whether resveratrol, a polyphenol phytoalexin, can be used to prevent RIN. For this purpose, in vitro experiments were performed using a human renal proximal tubule epithelial cell line (HK-2 cells). Following treatment for 48 h, the highly toxic radiocontrast agent, ioxitalamate, exerted cytotoxic effects on the HK-2 cells in a concentration-dependent manner, as shown by MTT assay. The half maximal inhibitory concentration (IC50) was found to be approximately 30 mg/ml. Flow cytometry also revealed a marked increase in the number of apoptotic cells following exposure to ioxitalamate. In addition, the number of necrotic, but not necroptotic cells was increased. However, treatment with resveratrol (12.5 µM) for 48 h significantly alleviated ioxitalamate (30 mg/ml)-induced cytotoxicity, by reducing cytosolic DNA fragmentation, increasing the expression of the anti-apoptotic protein, Bcl-2 (B-cell lymphoma 2), and survivin, activating caspase-3, preventing autophagic death and suppressing the production of reactive oxygen species (ROS). Resveratrol also suppressed the ioxitalamate-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage. N-acetylcysteine (NAC), a ROS scavenger commonly used to prevent RIN, also reduced ioxitalamate-induced cytotoxicity, but at a high concentration of 1 mM. Sirtuin (SIRT)1 and SIRT3 were not found to play a role in these effects. Overall, our findings suggest that resveratrol may prove to be an effective adjuvant therapy for the prevention of RIN.

Effectiveness of neoadjuvant concurrent chemoradiotherapy versus up-front proctectomy in clinical stage II-III rectal cancer: A population-based study.

AIMS: Neoadjuvant concurrent chemoradiotherapy (NCCRT) is currently the preferred treatment for rectal cancer of clinical stage II-III based on its efficacy in clinical trials. The population-based effectiveness of NCCRT is rarely reported on in the literature. The purpose of our study is to investigate the nationwide population-based effectiveness of NCCRT as compared with up-front proctectomy. METHODS: In this retrospective cohort study, we identified the study population by linking datasets including the cancer registry, death registry and other related files in Taiwan. We identified all patients with rectal adenocarcinoma of American Joint Committee on Cancer clinical stage II or III who were diagnosed in 2007 or 2008 and received either NCCRT or up-front proctectomy. We included patients' age, gender, residence, socioeconomic status and clinical stage as covariables. We used overall survival as the measure of effectiveness. The Cox proportional-hazards regression model was used for statistical analyses. We further conducted sensitivity analyses, one in only those who received optimal postoperative chemotherapy and one in two subgroups matched for propensity score. RESULTS: We included 1933 patients (NCCRT: 424; up-front proctectomy: 1509) in the study population. NCCRT was associated with improved survival as compared with up-front proctectomy (adjusted hazard ratio of death 0.656; 95% confidence interval 0.495-0.871). Our results were robust in the sensitivity analyses. CONCLUSION: We demonstrated that the use of neoadjuvant concurrent systemic therapy and radiotherapy is associated with better effectiveness in rectal adenocarcinoma of clinical stage II-III as compared with up-front proctectomy. Further studies are needed to elucidate the subgroups most likely to benefit and to clarify NCCRT's cost-effectiveness.

Increased risks of mortality and atherosclerotic complications in incident hemodialysis patients subsequently with bone fractures: a nationwide case-matched cohort study.

BACKGROUND: Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown. METHODS: Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up. RESULTS: After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx. CONCLUSIONS: The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications.

Long-term outcomes of dialysis patients after coronary revascularization: a population-based cohort study in Taiwan.

BACKGROUND AND AIMS: The outcomes of Chinese patients undergoing dialysis after coronary revascularization are unknown. We examined the outcomes of Taiwanese dialysis patients after coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or coronary stenting. METHODS: Using data from the National Health Research Institute database, we determined the outcomes of 1,287 dialysis patients who underwent initial coronary revascularization between 1997 and 2008. RESULTS: The 7-year overall survival rates were 69 ± 4%, 68 ± 3%, and 57 ± 2% for the CABG, stent, and PTCA patients (p = 0.001), respectively. After demographic and comorbidity adjustment, hazard ratios (HRs) for all-cause death in the CABG (vs. PTCA) and stent (vs. PTCA) patients were 0.695 (p = 0.015) and 0.721 (p = 0.009). Additionally, no significant difference in all-cause death was found between the CABG and stent patients. Moreover, the ≥65-year-old CABG group patients and the <65-year-old coronary stent group patients showed better survival than the PTCA group patients. Compared with the PTCA and CABG groups, the coronary stent group was significantly associated with a higher risk for recurrent acute myocardial infarction (AMI). Based on age stratification, the ≥65-year-old stent group had a higher risk for recurrent AMI than the PTCA group (HR, 1.562; p = 0.026). CONCLUSIONS: Chinese patients undergoing dialysis who underwent CABG or coronary stenting had better survival than those who underwent PTCA. Moreover, being ≥65 years old, CABG shows better survival compared with PTCA; being <65 years old, coronary stenting show better survival compared with PTCA.

Hemorrhagic cholecystitis after anticoagulation therapy.

Hemorrhagic cholecystitis is a rare and potentially fatal complication of biliary tract disease. Nontraumatic hemorrhagic cholecystitis is related to a variety of etiologies. Here, the authors reported an elderly patient who developed hemorrhagic cholecystitis after heparin and aspirin usage for unstable angina. Laparoscopic cholecystectomy was performed with the histopathology report disclosing adenocarcinoma in situ. As demonstrated in this case, underlying malignant changes in its early stage increase the risk of bleeding concomitant with anticoagulation usage.