The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. In vitro, we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. In vivo, we demonstrate NLRP3 is activated in urothelia from a genetic type 1 diabetic mouse (Akita) by week 15. We then bred an NLRP3 2/2 genotype into these mice and found this blocked bladder inflammation and cystometric markers of DBD. Analysis of bladder innervation established an NLRP3-dependent decrease in overall nerve density and Ad-fibers in the bladder wall along with an increase in C-fiber populations in the urothelia, which potentially explains the decreased sense of bladder fullness reported by patients and overactivity detected early in DBD. Together, the results demonstrate the role of NLRP3 in the genesis of DBD and suggest specific NLRP3-mediated neuronal changes can produce specific DBD symptoms.
IntroductionConstraints on surgical resident training (work-hour mandates, shorter training programs, etc.) and availability of expert surgical educators may limit the acquisition of prosthetic surgical skills. As a result, training courses are being conducted to augment the prosthetic surgery learning experience.AimTo evaluate the impact of a hands-on cadaver-based teaching program on resident procedural knowledge and procedural confidence with placement of a penile prosthesis.Main Outcome MeasureChanges in procedural knowledge and self-confidence following a focused training program on penile prosthetics.MethodsAs part of the 2017 Society of Urologic Prosthetic Surgeons and the Sexual Medicine Society of North America Annual Meeting, 31 urology residents participated in a simulation lab in prosthetic urology. The lab included didactic lectures and a hands-on cadaveric laboratory. Participants completed surveys before and after the course. Wilcoxon Signed Rank tests for matched pairs were used to compare respondents’ pre- and postcourse knowledge (% questions answered correctly) and confidence ratings. Prior implant experience was assessed.Results31 residents participated in this study. The majority of the participants were 4th- (41.9%) and 5th-year residents (38.7%). Participants showed a significant improvement in procedural knowledge test scores (68.8±13.4 vs 74.2 ± 13.0, P < .05) and self-reported increased median surgical confidence levels (4 vs 3, P value < .001) after completion of the cadaveric course. Subgroup analysis demonstrated that residents with prosthetic surgery experience of <10 cases benefited the most. In addition, improvement in surgical confidence levels observed was greater than the improvement in surgical knowledge. The overall cost of the simulation training course was approximately $1,483 per resident.ConclusionSimulation training in prosthetic surgery seems to improve surgical confidence and knowledge. Further research is needed to better understand the benefits and limitations of simulation training.Lentz AC, Rodríguez D, Davis LG. Simulation training in penile implant surgery: Assessment of surgical confidence and knowledge with cadaveric laboratory training. Sex Med 2018;6:332–338.
BackgroundDue to their location away from the nerve bundles, anterior prostate cancers (APC) represent a rational target for image-guided cryoablation. This report describes the feasibility and short-term outcomes of anterior focal cryosurgery.MethodsA retrospective review between 2012 and 2016 of patients with clinically localized APC treated with anterior gland cryoablation was performed. Descriptive statistics were used to report: age, PSA, prostate volume, prostate cancer grade group (PGG), median time to follow-up, and changes in functional status measured with the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) score.ResultsA total of 17 patients underwent anterior focal cryoablation with a median follow-up of 15 months. Median age and PSA at diagnosis were 67 years and 8.7 ng/mL. Pre-operative PGG1 was identified in 12 (71%) men and PGG2 in 5 (29%) men. Median (IQR) lesion volume was 2 mL(0.86, 3.1). Preoperative median IIEF-5 and IPSS scores were 19.5 and 5, and decreased to 19 and 4, post-operatively. All patients remained continent with no change in sexual function. All post-procedure targeted biopsies of the treated cancers were negative.ConclusionOur pilot study demonstrates the feasibility of treating APCs with image-guided targeted focal cryoablation as a good balance between short-term oncologic control and near complete preservation of genitourinary function. Further follow-up is necessary to examine the potential benefits long-term.
Introduction: Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables. Materials and Methods: We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specifi c data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves. Results: We identifi ed 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P <0.0001) were signifi cantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72. Conclusion: Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.
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