Objective Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Design 70 treatment-naïve patients were randomized to 4 weeks of ribavirin (1000–1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were also randomized to a liver biopsy 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results After four weeks of ribavirin monotherapy, HCV levels decreased by 0.5±0.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting ISG induction by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion Ribavirin is a weak antiviral but its clinical effect seems to be mediated by a separate, indirect mechanism, which may act to reset interferon-responsiveness in HCV-infected liver.

ObjectivesTo incorporate and validate clinically relevant performance metrics of simulation (CRPMS) into a hydrogel model for nerve-sparing robot-assisted radical prostatectomy (NS-RARP). Materials and MethodsAnatomically accurate models of the human pelvis, bladder, prostate, urethra, neurovascular bundle (NVB) and relevant adjacent structures were created from patient MRI by injecting polyvinyl alcohol (PVA) hydrogels into threedimensionally printed injection molds. The following steps of NS-RARP were simulated: bladder neck dissection; seminal vesicle mobilization; NVB dissection; and urethrovesical anastomosis (UVA). Five experts (caseload >500) and nine novices (caseload <50) completed the simulation. Force applied to the NVB during the dissection was quantified by a novel tension wire sensor system fabricated into the NVB. Post-simulation margin status (assessed by induction of chemiluminescent reaction with fluorescent dye mixed into the prostate PVA) and UVA weathertightness (via a standard 180-mL leak test) were also assessed. Objective scoring, using Global Evaluative Assessment of Robotic Skills (GEARS) and Robotic Anastomosis Competency Evaluation (RACE), was performed by two blinded surgeons. GEARS scores were correlated with forces applied to the NVB, and RACE scores were correlated with UVA leak rates. Incorporating clinical metrics in a RARP model sparing radical prostatectomy and fruit for simple prostatectomy. Korean J Urol 2011; 52: 130-5 34 Clarebrough E, Christidis D, Lindner U, Fernandes K, Fleshner N, Lawrentschuk N. Analysis of a practical surgical skills laboratory for nerve sparing radical prostatectomy. World J Urol 2019; 37: 799-804

Intermittent hypoxia in obstructive sleep apnea causes oxidative stress with ultrastructural and functional changes in the bladder. Sleep apnea related nocturia/voiding symptoms could be the result of these direct changes. Untreated sleep apnea has significant health consequences. Identifying urinary oxidative stress products in patients with nocturia may be useful as an economical noninvasive biomarker to identify undiagnosed obstructive sleep apnea.