Do patients with Peyronie's disease perceive penile curvature in adults and children differently than the general population?

BACKGROUND: As perception of penile curvature varies widely, we sought to understand how adults perceive curvature and how these opinions compare with those of patients with curvature, specifically Peyronie's disease (PD). AIM: To investigate the perspectives of curvature correction from adults with and without PD, as well as differences within demographics. METHODS: A cross-sectional survey was administered to adult patients and nonpatient companions in general urology clinics at 3 institutions across the United States. Men, women, and nonbinary participants were recruited. Patients were grouped as having PD vs andrology conditions without PD vs general urology conditions plus companions. The survey consisted of unlabeled 2-dimensional images of penis models with varying degrees of curvature. Participants selected images that they would want surgically corrected for themselves and their children. Univariable and multivariable analyses were performed to identify demographic variables associated with willingness to correct. OUTCOMES: Our main outcome was to detect differences in threshold to correct curvature between those with and without PD. RESULTS: Participants were grouped as follows: PD (n = 141), andrology (n = 132), and general (n = 302) . Respectively, 12.8%, 18.9%, and 19.9% chose not to surgically correct any degree of curvature (P = .17). For those who chose surgical correction, the mean threshold for correction was 49.7°, 51.0°, and 51.0° (P = .48); for their children, the decision not to correct any degree of curvature was 21.3%, 25.4%, and 29.3% (P = .34), which was significantly higher than correction for themselves (P < .001). The mean threshold for their children's correction was 47.7°, 53.3°, and 49.4° for the PD, andrology, and general groups (P = .53), with thresholds no different vs themselves (P = .93). On multivariable analysis, no differences were seen in demographics within the PD and andrology groups. In the general group, participants aged 45 to 54 years and those who identified as LGBTQ (lesbian, gay, bisexual, transgender, queer) had a higher threshold for correction as compared with their counterparts when factoring other demographic variables (63.2° vs 48.8°, P = .001; 62.1° vs 50.4°, P = .05). CLINICAL IMPLICATIONS: With changing times and viewpoints, this study stresses the importance of shared decision making and balancing risks and benefits to correction of penile curvature. STRENGTHS AND LIMITATIONS: Strengths include the broad population surveyed. Limitations include the use of artificial models. CONCLUSION: No significant differences were seen in the decision to surgically correct curvature between participants with and without PD, with participants being less likely to choose surgical correction for their children.

Concordance of Narrative Comments with Supervision Ratings Provided During Entrustable Professional Activity Assessments.

BACKGROUND: Use of EPA-based entrustment-supervision ratings to determine a learner's readiness to assume patient care responsibilities is expanding. OBJECTIVE: In this study, we investigate the correlation between narrative comments and supervision ratings assigned during ad hoc assessments of medical students' performance of EPA tasks. DESIGN: Data from assessments completed for students enrolled in the clerkship phase over 2 academic years were used to extract a stratified random sample of 100 narrative comments for review by an expert panel. PARTICIPANTS: A review panel, comprised of faculty with specific expertise related to their roles within the EPA program, provided a "gold standard" supervision rating using the comments provided by the original assessor. MAIN MEASURES: Interrater reliability (IRR) between members of review panel and correlation coefficients (CC) between expert ratings and supervision ratings from original assessors. KEY RESULTS: IRR among members of the expert panel ranged from .536 for comments associated with focused history taking to .833 for complete physical exam. CC (Kendall's correlation coefficient W) between panel members' assignment of supervision ratings and the ratings provided by the original assessors for history taking, physical examination, and oral presentation comments were .668, .697, and .735 respectively. The supervision ratings of the expert panel had the highest degree of correlation with ratings provided during assessments done by master assessors, faculty trained to assess students across clinical contexts. Correlation between supervision ratings provided with the narrative comments at the time of observation and supervision ratings assigned by the expert panel differed by clinical discipline, perhaps reflecting the value placed on, and perhaps the comfort level with, assessment of the task in a given specialty. CONCLUSIONS: To realize the full educational and catalytic effect of EPA assessments, assessors must apply established performance expectations and provide high-quality narrative comments aligned with the criteria.

Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism.

PURPOSE: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. MATERIALS AND METHODS: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. RESULTS: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. CONCLUSIONS: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.

What is the Role of the Oncology Nurse in Fertility Preservation Counseling and Education for Young Patients?

Oncology nurses are uniquely positioned to offer fertility preservation counseling and education for cancer patients of reproductive age, yet there is a dearth of research that focuses on current practice and perceptions of nursing role. In 2013, the American Society of Clinical Oncology extended the duties of fertility preservation counseling among patients of reproductive age undergoing cancer treatment to include registered nurses and other allied health professionals as active partners in the counseling and education process. This study used a cross-sectional descriptive survey to assess current practices, role perceptions, and barriers to fertility preservation counseling among registered nurses working in an academic care setting with outpatient and inpatient services. There were significant gaps in current practices and perceptions of roles regarding fertility preservation counseling. Many nurses expressed the perception that fertility preservation counseling was important, but it was outside the scope of their practice to perform this education. This preliminary work defined need for an interdisciplinary fertility preservation team, communication surrounding educational practice norms, and designated oncofertility navigator.

A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

PURPOSE: We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. MATERIALS AND METHODS: In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. RESULTS: Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. CONCLUSIONS: The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism.

Prognostic implications of immediate PSA response to early salvage radiotherapy.

INTRODUCTION: Up to 25% of men with prostate cancer who undergo radical prostatectomy will recur. In this setting, salvage radiotherapy may cure patients with local recurrence, but is unable to cure those with occult metastatic disease. The objective of this study is to examine how prostate-specific antigen (PSA) response to radiotherapy predicts subsequent disease progression and survival. MATERIALS AND METHODS: Using a prospectively populated database of 3089 men who underwent open radical prostatectomy, 212 patients (7%) were identified who received early salvage radiotherapy for biochemical recurrence. The main outcome was time to disease progression after salvage radiotherapy. Patients were stratified by PSA response after radiotherapy: 1) PSA < 0.1 ng/mL, 2) persistently detectable PSA, and 3) rising PSA. RESULTS: Patients received salvage radiotherapy at a median PSA of 0.20 ng/mL (IQR 0.10-0.30 ng/mL). At a median follow up of 47.3 months, a total of 52 (25%) patients experienced disease progression. On multivariable analysis, both persistent PSA (HR 5.12; 95% CI 1.98-13.23) and rising PSA (HR 16.55; 95% CI 6.61-41.48) were associated with increased risk of disease progression compared to those with PSA < 0.1 ng/mL after adjusting for pre-radiotherapy PSA, Gleason score, margin status, stage, and time to radiotherapy. Only rising PSA was associated with an increased risk of cancer-specific and all-cause mortality. CONCLUSIONS: PSA response is associated with the risk of disease progression following salvage radiotherapy. This information can be used to counsel patients on the potential need for additional therapy and identify those at greatest risk for progression and cancer-related mortality.

Alterations in microRNA expression in a murine model of diet-induced vasculogenic erectile dysfunction.

INTRODUCTION: MicroRNAs (miRs) are noncoding, endogenous RNA molecules that regulate gene expression and play roles in response to vascular injury. AIM: The aim of this study was to identify miRs expressed in corporal tissue (CT) and to determine whether miRs demonstrate differential expression in a mouse model of diet-induced erectile dysfunction (ED). METHODS: RNA was isolated from the CT from control mice and mice with diet-induced ED. A quantifiable miR profiling technique (NanoString) was used to determine the expression of over 600 miRs. MAIN OUTCOME MEASURES: Differential expression analysis was performed using a negative binomial regression model for count-based data. Mean expression levels, fold change, and false discovery-corrected P values were determined. Candidate miRs were validated via quantitative polymerase chain reaction (Q-PCR). RESULTS: In control mice, NanoString analysis revealed that 181 miRs were expressed above background levels and 5 miRs were expressed at high levels. Diet-induced ED resulted in the up-regulation of 6 miRs and the down-regulation of 65 miRs in the CT compared with mice on control diet. Focusing on the upregulated miRs, we chose five for Q-PCR validation. Of these five, two (miR-151-5p and miR-1937c) demonstrated significance via Q-PCR, whereas the other three (miR-720, miR-1937a, miR-205) trended in the correct direction. CONCLUSIONS: MiRs may play a significant role in mRNA regulation in CT and specific miRs may be involved in diet-induced vasculogenic ED. Future studies are aimed at determining the mRNA targets of these miRs.

Sequencing methods and datasets to improve functional interpretation of sleeping beauty mutagenesis screens.

BACKGROUND: Animal models of cancer are useful to generate complementary datasets for comparison to human tumor data. Insertional mutagenesis screens, such as those utilizing the Sleeping Beauty (SB) transposon system, provide a model that recapitulates the spontaneous development and progression of human disease. This approach has been widely used to model a variety of cancers in mice. Comprehensive mutation profiles are generated for individual tumors through amplification of transposon insertion sites followed by high-throughput sequencing. Subsequent statistical analyses identify common insertion sites (CISs), which are predicted to be functionally involved in tumorigenesis. Current methods utilized for SB insertion site analysis have some significant limitations. For one, they do not account for transposon footprints - a class of mutation generated following transposon remobilization. Existing methods also discard quantitative sequence data due to uncertainty regarding the extent to which it accurately reflects mutation abundance within a heterogeneous tumor. Additionally, computational analyses generally assume that all potential insertion sites have an equal probability of being detected under non-selective conditions, an assumption without sufficient relevant data. The goal of our study was to address these potential confounding factors in order to enhance functional interpretation of insertion site data from tumors. RESULTS: We describe here a novel method to detect footprints generated by transposon remobilization, which revealed minimal evidence of positive selection in tumors. We also present extensive characterization data demonstrating an ability to reproducibly assign semi-quantitative information to individual insertion sites within a tumor sample. Finally, we identify apparent biases for detection of inserted transposons in several genomic regions that may lead to the identification of false positive CISs. CONCLUSION: The information we provide can be used to refine analyses of data from insertional mutagenesis screens, improving functional interpretation of results and facilitating the identification of genes important in cancer development and progression.

Impact of the 2012 American Urological Association vasectomy guidelines on post-vasectomy outcomes.

PURPOSE: The 2012 American Urological Association (AUA) vasectomy guidelines recommend the finding of rare nonmotile sperm, representing 100,000 or fewer nonmotile sperm per ml, as a metric of post-vasectomy success. At our institution success was previously defined as 2 sequential azoospermic centrifuged semen pellets. The criteria change of including rare nonmotile sperm as a success end point may simplify post-vasectomy followup and decrease the number of post-vasectomy semen analyses required to assure occlusive success. MATERIALS AND METHODS: In the context of the new 2012 guidelines we retrospectively reviewed and analyzed the records of 972 of the 1,740 vasectomies (55.9%) performed between January 2000 and June 2012 after which at least 1 post-vasectomy semen analysis was done. RESULTS: A total of 1,919 post-vasectomy semen analyses were obtained from 972 patients with a mean ± SE age of 39.7 ± 0.2 years. Occlusive success was evident in 337 azoospermic men (36.4%), while 514 (52.9%) underwent 2 or more post-vasectomy semen analyses and 458 (47.1%) returned for a single post-vasectomy semen analysis but were lost to followup. Of these noncompliant patients 76.0% were azoospermic, 19.7% had rare nonmotile sperm, 1.5% had greater than 100,000 nonmotile sperm per ml and 2.8% had motile sperm. Three patients underwent repeat vasectomy for persistent rare nonmotile sperm. If the criteria defined by the 2012 guidelines had been used to monitor these men, the occlusive success rate would have improved to 97.6% (949 patients) (p <0.05). Repeat vasectomies as well as 896 subsequent post-vasectomy semen analyses would have been avoided. CONCLUSIONS: The AUA vasectomy guidelines provide clear, evidence-based criteria for vasectomy success. The guidelines simplify followup protocols, improve patient compliance and help avoid unnecessary post-vasectomy semen analyses and repeat vasectomies.

Patient satisfaction with testosterone replacement therapies: the reasons behind the choices.

INTRODUCTION: Testosterone replacement therapy (TRT) for male hypogonadism is rapidly gaining popularity and acceptance. Options include gels, injections, and implantable subcutaneous pellets. AIMS: The aim of this study was to determine rates of patient satisfaction and reasons for patient preferences in hypogonadal men on TRT. METHODS: An anonymous, prospective survey was distributed to men presenting for TRT at an academic urology clinic. The survey was organized into multiple domains including patient satisfaction and treatment motivation. MAIN OUTCOME MEASURES: Patient satisfaction responses obtained via anonymous survey. RESULTS: Average patient age was 49 ± 0.7 years (n = 382). Injectable testosterone was chosen by 53%, gel-based regimens by 31%, and pellets by 17%. Overall, 70% of patients were satisfied with their TRT and 14% reported dissatisfaction. Satisfaction rates were similar between gels (68%), injections (73%), and implantable pellets (70%). Doctor recommendation was the sole significant reason for patients preferring gel-based TRT (66% vs. 37% injection users vs. 31% pellet users). Injectable TRT was favored because of lower cost (35% vs. 21% gel users vs. 19% pellet users). Pellets were favored for ease of use (64% vs. 44% injection users vs. 43% gel users) and convenience (58% vs. 26% injection users vs. 19% gel users). Pellets had increased rates of satisfaction within the first 12 months. Improvements in concentration and mood occurred at higher percentages in satisfied patients. CONCLUSIONS: Patients are satisfied with TRT. Lower costs are important to patients on injections. Convenience and ease of use are central in choosing pellet therapy. Men on TRT should be questioned about mood and concentration because these factors exhibited the greatest improvements in satisfied patients.

The role of regulatory proteins and S-nitrosylation of endothelial nitric oxide synthase in the human clitoris: implications for female sexual function.

INTRODUCTION: During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. AIM: To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. METHODS: Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. CONCLUSIONS: Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.

The significance of sperm heads and tails within the vasal fluid during vasectomy reversal.

INTRODUCTION: The finding of only sperm heads and/or short tails (SHST) during vasectomy reversal (VR) creates a difficult decision for the best method of vasal reconstruction, i.e. vasovasostomy (VV) or epididymovasostomy (EV). Using outcome analyses, we report the impact of SHST alone and combined with qualitative analysis of gross fluid quality in predicting successful VR. MATERIALS AND METHODS: The records of 356 men who underwent VR by a single surgeon from 2005 to 2012 were retrospectively reviewed. Intravasal fluid was assessed for gross quality (i.e., clear, opaque, pasty or creamy) as well as microscopic composition (i.e., motile or non-motile whole sperm, SHST or no sperm). The post-operative patency rates and semen analysis parameters were assessed. RESULTS: Fourteen men (3.9%) demonstrated SHST bilaterally in the vasal fluid. The median duration from vasectomy was 6.0 years (interquartile range 4.0-9.8). Bilateral VVs were performed on 12 men (86%), while two men (14%) had a unilateral VV and a contralateral EV. Of the 26 vasa undergoing VR, the majority of the fluid quality was classified as creamy (n = 20 vasa, 76.9%). The remaining fluid was classified as pasty (n = 3 vasa, 11.5%), opaque (n = 2 vasa, 7.7%) and clear (n = 1 vasa, 3.8%). In cases undergoing bilateral VV with only SHST, patency rates were 90.9%, and both cases of unilateral EV were patent (100%). CONCLUSIONS: VV was successful in 90.9% of patients undergoing VR in the setting of SHST alone. Even when creamy or pasty fluid was present, the results surpassed the expected patency rate for an EV. Therefore, the presence of only SHST, regardless of fluid quality, should not dissuade the surgeon from performing a VV. CONCLUSIONS: VV was successful in 90.9% of patients undergoing VR in the setting of SHST alone. Even when creamy or pasty fluid was present, the results surpassed the expected patency rate for an EV. Therefore, the presence of only SHST, regardless of fluid quality, should not dissuade the surgeon from performing a VV.

Redefining bladder neck dose in low-dose-rate prostate brachytherapy-Can we improve urinary toxicity without impacting disease control?

BACKGROUND: We sought to assess the impact of bladder neck dose (BND) on patient reported urinary toxicity, and feasibility of relative urethral sparing technique in prostate brachytherapy (PB). METHODS AND MATERIALS: We retrospectively identified bladder neck as a point dose on post-implant CT scans in patients treated with 131Cs PB. Urinary symptoms were assessed through EPIC questionnaires. Patient cohorts were identified based on mean BND as a percentage of prescription dose with toxicity assessment at each time point. RESULTS: In our cohort of 542 patients, BND was associated with clinically significant acute urinary symptoms and chronic symptoms, as patients receiving >70% of the prescription dose had significantly worse overall EPIC scores than patients receiving ≤70% of prescription dose. There was no difference in bDFS between patients receiving BND ≤70% (96% bDFS) and >70% (94% bDFS) at a median follow up of 57 months. CONCLUSIONS: BND has a significant impact on both acute and chronic urinary symptoms, with reduced symptoms reported with BND <70% of prescription dose. With a median follow up of 4.7 years, excellent bDFS has thus far been achieved with relative urethral and bladder neck sparing. Utilizing this constraint should improve urinary symptoms without impacting disease control.

Can an in-person hands-on applicator-based teaching session improve trainee knowledge and comfort with complex gynecologic brachytherapy?

INTRODUCTION: With the emergence of imaged-based planning and hybrid applicators the complexity of gynecologic brachytherapy has dramatically increased. Despite the known advantages of brachytherapy, notable national declines in utilization of brachytherapy have been documented. Clearly improved education in the sphere of gynecologic brachytherapy is needed. We hypothesize that a hands-on applicator-based training session would improve trainee comfort with gynecologic brachytherapy. METHODS AND MATERIALS: An in-person, applicator-based, hands-on training session was held with trainees from both radiation and gynecologic oncology programs. Trainees practiced assembling and handling applicators while receiving instruction on clinical scenarios in which various applicators are used in gynecologic cancer brachytherapy. Pre- and post-session, participants were administered an objective test of 10 pictorial-based case vignettes to quantify ability to select the correct applicator based on the interpretation of T2-weighted MR images. Participants additionally received a subjective survey to quantify comfort and experience with gynecologic brachytherapy using Likert-type question formatting. RESULTS: A total of 14 trainees participated. Most common case volume experience was 0-10 intracavitary (57%), 0-10 hybrid (71%), and 0-10 interstitial (71%). Pre-session, the most common answer to comfort level was "not comfortable still learning" for all brachytherapy types, and most common answer to largest gap in knowledge was all facets of brachytherapy. Average case-based test score was 3.5/10 pre-session versus 5.3/10 post-session (p = 0.028). Post-session, all respondents reported improved comfort level with brachytherapy. Post-session, most common answer to largest gap in knowledge was applicator/patient selection, and applicator/patient selection was also the largest area of identified improvement. 100% of participants felt repeating the session in the future would be helpful. CONCLUSIONS: Hands-on training with applicators improves both subjective and objective comfort with gynecologic brachytherapy. With 100% of participants requesting to implement this session into resident training, we suggest national opportunities might exist to expand educational processes and improve utilization of complex gynecologic brachytherapy in practice.