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In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 &micro, g) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

Purpose: The purpose of this study was to report the feasibility, safety, and benefits of laparoscopic radical cystectomy (LRC) for patients with bladder cancer (BC) who are older than 75 years and with marginal cardiopulmonary function in a regional teaching hospital. Materials and Methods: The charts of thirty patients who underwent LRC between 2013 and 2016 in a community teaching hospital were reviewed. The patients were subgrouped into the age groups ≥75 years and

Objective: To examine the 10-year risk of stroke among patients with acute urinary retention (AUR) in Taiwan, using a population-based dataset. Methods: This retrospective cohort study included 38,433 patients aged > 50 years with AUR, with or without catheterization, and 38,433 matched patients without AUR (controls) sourced from the Longitudinal Health Insurance Database from 2001 to 2010. Cox proportional hazards regression was used to evaluate the association between AUR and the risk of stroke during the subsequent 10-year follow-up period, after adjusting for sociodemographic characteristics, hypertension, diabetes, hyperlipidemia, coronary heart disease, and urinary tract infection. Results: Of the 38,433 patients with AUR, 2805 (7.3%) had strokes during the follow-up period compared with 1077 (2.8%) controls (crude hazard ratio, 2.69; 95% confidence interval, 2.5–2.88). After adjusting for potential confounders, risk of stroke was increased in patients with AUR (hazard ratio, 2.36; 95% confidence interval, 2.19–2.53). There was a significant difference in the 10-year stroke-free survival rate between the patients with and without AUR (p

Background Diet is associated with self-reported indices of sexual health. The mechanisms responsible for these changes remain poorly understood. Aim To investigate the hemodynamic and histological impact of dietary change in a rat model of hyperlipidemia-associated erectile dysfunction. Methods 40 2-month old male Sprague–Dawley rats were divided into 4 groups. 10 rats were fed a diet of standard chow and served as negative controls (N group). The remaining 30 age-matched rats were divided at random into 3 groups: (i) high-fat diet for 5 months starting at age 5 months (H group); (ii) high-fat diet for 5 months starting at age 4 months followed by 1 month of standard chow (H+N1M group); and (iii) high-fat diet for 5 months starting at age 2 months followed by 3 months of standard chow (H+N3M group). All rats underwent erectile function testing and sacrifice at age 10 months. Outcomes Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured to evaluate erectile function. Blood samples were collected to measure serum testosterone and lipid levels, and penile tissue specimens were obtained for histological examination. Results Total body weight, low-density lipoprotein, and serum glucose were significantly higher in the H group compared with the N and H+N3M groups. Serum high-density lipoprotein level was significantly lower in the H group compared with the N and H+N3M groups. The mean ICP/MAP ratio was significantly lower in the H group compared with the N and H+N3M groups (0.33 ± 0.05 vs 0.79 ± 0.07 vs 0.73 ± 0.13; P < .05 for both). Markers for intracorporal neuronal nitric oxide synthase and endothelial cells were more weakly expressed in the H group compared with the N and H+N3M groups. There was no significant difference in smooth muscle content among the groups. Mean cavernosal oxidative stress and the apoptotic index were significantly higher in the H group compared with the N and H+N3M groups. No significant between-group differences were noted with respect to serum testosterone; the H group had significantly higher serum glucose and low-density lipoprotein levels, effects that were partially mitigated in the H +N1M and H+N3M groups. Clinical Translation Administration of a healthy diet is associated with normalization of functional and histological penile defects associated with a high-fat diet. Strengths & Limitations Metabolic changes were clearly linked to functional improvements in penile blood flow. Differences between rat and human lipoprotein metabolism are a limitation of this study. Conclusion Dietary changes may have positive effects on penile hemodynamics in a rat model of hyperlipidemia-associated erectile dysfunction.

Objective The purpose of this study was to report the feasibility, safety, and benefits of laparoscopic radical cystectomy (LRC) for patients with bladder cancer who are older than 75 years and with marginal cardiopulmonary function in a regional teaching hospital. Materials and methods The charts of 30 patients who underwent LRC between 2013 and 2016 in a community teaching hospital were reviewed. The patients were sub-grouped into the age groups ≥75 years and Results A significant difference was observed in the data of the group ≥75 years group compared with the p = 0.0007) and higher rate of marginal cardiopulmonary function (80% vs. 26.7%, p = 0.0092). No significant difference was observed in sex, CCI score (3.93 vs. 3.27), Body Mass Index (BMI) (24.8 vs. 24.4), ejection fraction (69% vs. 70.97%), operation time (473 vs. 465 min), blood loss (503 vs. 380 mL), urinary diversion type, intensive care unit care (1.13 vs. 0.6 days), interval to ambulation (2 vs. 1.8 days), interval to oral food intake (3.2 vs. 2.6 days), interval to normal bowel function (4.6 vs. 3.6 days), post-op hospitalization (15.67 vs. 11.67 days), and blood transfusion rate (33.3% vs. 26.7%) between the two groups. No conversion to open surgery or mortality was observed. Surgical complications occurred in 15 patients, with a complication rate of 50%. No surgical mortality was noted in 30 or 90 days. Most pathological cases revealed urothelial carcinoma. Conclusions LRC is a safe option with favorable outcomes in bladder cancer patients older than 75 years with marginal cardiopulmonary function in a regional teaching hospital.

INTRODUCTION AND OBJECTIVES: Radium Ra 223 dichloride (Ra-223), an intravenous alpha-emitting radioisotope, is a calcium mimetic, forming complexes with hydroxyapatite at sites of bone metastasis for castration-resistant prostate cancer (mCRPC) patients. Abiraterone Acetate (AA), an oral androgen biosynthesis inhibitor, decreases serum testosterone for mCRPC patients. This study evaluates safety and quality of life of concurrent use of these FDA approved CRPC therapies, and is the largest cohort of subjects reported to date. METHODS: This open-label, phase II study (NCT02097303), enrolled subjects with symptomatic bone mCRPC. Subjects were assessed at baseline, day 1 of each of 6 cycles and 30 days post final Ra-223 treatment. Primary objectives were quality of life and bone pain measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Bone Pain Index Short Form (BPI-SF). Secondary objectives were adverse events (AE), disease progression, performance status, total alkaline phosphatase, prostate specific antigen, skeletal related events, and more antineoplastic therapy. Safety data were analyzed for all with >/1⁄4 1 infusion of Ra-223. RESULTS: 31 of 37 enrolled subjects completed the study and received Ra-223 every 4 weeks x 6 doses. + 28/37 received AA 1000 mg QD; 3/37 required dose reduction. All subjects received prednisone 5 mg BID. Median AA use before first Ra-223 dose was 31 days [95% CI 24.2-37.8]. Subjects had significant improvements in FACT-P Prostate subscales and no significant increases in pain. They reported significant pain relief from treatment. 19/31 had radiographic disease improvement or stability. Secondary endpoints also showed benefit of the combined treatment. ECOG scores remained stable. Subjects reported 72 AEs related to treatment; 44, 26, and 2 were grade 1, 2, and 3, respectively. Common AEs were fatigue and gastrointestinal issues. 4 SAEs were reported; 1 abdominal pain possibly related to AA and 3 non-related to treatment, including one death. CONCLUSIONS: This prospective trial of Radium 223 and Abiraterone Acetate confirms an overall improvement in Quality of Life, and demonstrates tolerability of synergistic use of the approved mCRPC agents. Source of Funding: Bayer Healthcare Pharmaceuticals, Inc. Statistical Analysis Provided By: Department of Data Management & Statistical Analysis, American Urological Association.

Objectives: Atherosclerosis may lead to chronic bladder ischemia, which eventually results in lower urinary tract symptoms (LUTS). Patients with venous thromboembolism (VTE) have a higher prevalence of atherosclerosis. Methods: A total of 31,559 patients had been diagnosed with or without LUTS between 2000 and 2010 in Taiwan National Health Insurance Research Database, each was enrolled in the LUTS and non-LUTS cohorts, respectively. The risk of VTE in LUTS and non-LUTS cohorts was calculated by Cox proportional hazards regression model. Results: After adjustment for age, sex, and comorbidities, the risk of subsequent VTE was 1.34-fold higher in the LUTS than in the non-LUTS cohort. The adjusted risk of VTE was highest in patients with LUTS with any comorbidity. The age-specific relative risk of VTE was significantly higher in patients aged ≥50 years, particularly in those aged 50–64 years, in the LUTS than in the non-LUTS cohort. Conclusions: LUTS is a risk factor for VTE. Physicians should consider the possibility of underlying VTE in patients aged ≥50 years having cardiovascular comorbidities.