Effectiveness of Liposomal Bupivacaine With Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Local Anesthetic for Children Undergoing Ambulatory Urologic Surgery: The Baby ORIOLES Randomized Clinical Trial.

PURPOSE: We sought to determine if the addition of liposomal bupivacaine to bupivacaine hydrochloride improves opioid-free rate and postoperative pain scores among children undergoing ambulatory urologic surgery. MATERIALS AND METHODS: A prospective, phase 3, single-blinded, single-center randomized trial with superiority design was conducted in children 6 to 18 years undergoing ambulatory urologic procedures between October 2021 and April 2023. Patients were randomized 1:1 to receive dorsal penile nerve block (penile procedures) or incisional infiltration with spermatic cord block (inguinal/scrotal procedures) with weight-based liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The primary outcome was opioid-free rate at 48 hours. Secondary outcomes included parents' postoperative pain measure scores, numerical pain scale scores, and weight-based opioid utilization at 48 hours and 10 to 14 days. RESULTS: We randomized 104 participants, with > 98% (102/104) with complete follow-up data at 48 hours and 10 to 14 days. At interim analysis, there was no significant difference in opioid-free rate at 48 hours between arms (60% in the intervention vs 62% in the control group; estimated difference in proportion -1.9% [95% CI, -20%-16%]; P = .8). We observed no increased odds of patients being opioid-free at 48 hours with the intervention compared to the control group (OR 0.96 [95% CI 0.41-2.3]; P = .9). The trial met the predetermined futility threshold for early stopping. There was no difference in parents' postoperative pain measure scores, numerical pain scale scores, or opioid utilization at 48 hours or 10 to 14 days. No difference in adverse events was observed. CONCLUSIONS: The addition of liposomal bupivacaine to bupivacaine hydrochloride did not significantly improve opioid-sparing effect or postoperative pain compared with bupivacaine hydrochloride alone among children ≥ 6 years undergoing ambulatory urologic surgery.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR-CEST urography.

PURPOSE: To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. METHODS: The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3 ppm relative to the average pre-injection signal. RESULTS: For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). CONCLUSION: Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

PTEN Loss with ERG Negative Status is Associated with Lethal Disease after Radical Prostatectomy.

PURPOSE: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. RESULTS: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). CONCLUSIONS: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.

Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury.

BACKGROUND: Previous studies have documented improvement in erectile function after bilateral cavernous nerve injury (BCNI) in rats with the use of pioglitazone. Our group determined this improvement to be mediated by the insulin-like growth factor-1 (IGF-1) pathway. AIM: To eliminate the systemic effects of pioglitazone and evaluate the local delivery of IGF-1 by polymeric microspheres after BCNI in the rat. METHODS: Male Sprague-Dawley rats aged 10-12 weeks were assigned at random to 3 groups: sham operation with phosphate buffered saline (PBS)-loaded microspheres (sham group), crush injury with PBS-loaded microspheres (crush group), and crush injury with IGF-1-loaded microspheres (IGF-1 group). Poly(lactic-co-glycolic) acid microspheres were injected underneath the major pelvic ganglion (MPG). IGF-1 was released at approximately 30 ng/mL/day per MPG per rat. OUTCOMES: Functional results were demonstrated by maximal intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP). Protein-level analysis data of IGF-1 receptor (IGF-1R), extracellular signal-regulated kinase (ERK)-1/2, and neuronal nitric oxide synthase (nNOS) were obtained using Western blot analysis and immunohistochemistry for both the cavernosal tissue and the MPG and cavernous nerve (CN). RESULTS: At 2 weeks after nerve injury, animals treated with IGF-1 demonstrated improved erectile functional recovery (ICP/MAP) at all voltages compared with BCNI (2.5V, P = .001; 5V, P < .001; 7.5V, P < .001). Western blot results revealed that up-regulation of the IGF-1R and ERK-1/2 in both the nervous and erectile tissue was associated with improved erectile function recovery. There were no significant between-group differences in nNOS protein levels in cavernosal tissue, but there was an up-regulation of nNOS in the MPG and CN. Immunohistochemistry confirmed these trends. CLINICAL TRANSLATION: Local up-regulation of the IGF-1R in the neurovascular bed at the time of nerve injury may help men preserve erectile function after pelvic surgery, such as radical prostatectomy, eliminating the need for systemic therapy. STRENGTHS & LIMITATIONS: This study demonstrates that local drug delivery to the MPG and CN can affect the CN tissue downstream, but did not investigate the potential effects of up-regulation of the growth factor receptors on prostate cancer tissue. CONCLUSION: Stimulating the IGF-1R at the level of the CN has the potential to mitigate erectile dysfunction in men after radical prostatectomy, but further research is needed to evaluate the safety of this growth factor in the setting of prostate cancer. Haney NM, Talwar S, Akula PK, et al. Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury. J Sex Med 2019;16:383-393.

The Effect of Shift Work on Urogenital Disease: a Systematic Review.

PURPOSE OF REVIEW: Non-standard shift work schedules negatively impact the overall health of shift workers, and several studies have shown that shift work, specifically, is detrimental to urogenital health. The aims of this study are to systematically review the literature and determine the effect of shift work on the outcomes of hypogonadism, male infertility, lower urinary tract symptoms, and urogenital cancers. RECENT FINDINGS: Recent evidence supports associations between non-standard shift work and an increase in the frequency of prostate cancer and the severity of erectile dysfunction, lower urinary tract symptoms, and hypogonadal symptoms, as well as worsening of semen parameters and fertility. These associations are strengthened by the presence of shift work sleep disorder (SWSD) which affects up to 20% of shift workers. No studies have assessed the impact of shift work on the frequency or severity of nephrolithiasis, interstitial cystitis, pelvic pain, prostatitis, or urinary tract infections. Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent shift work sleep disorder. Recognition of these elevated risks among shift workers can aid in more effective screening for urologic conditions.

National Postoperative Opioid Prescribing Rates Following Pediatric Urology Procedures Before and After the 2018 American Academy of Pediatrics Challenge to Reduce Opioid Prescribing: A Claims Database Analysis.

OBJECTIVE: To evaluate trends in opioid prescribing rates following pediatric urologic surgery. METHODS: We queried the TriNetX Research database for patients under age 18 who underwent one of seven common pediatric urology procedures. We identified the proportion of patients that received an oral opioid prescription within 5days of surgery. The primary analysis evaluated the trend in postoperative opioid prescriptions using 3-month intervals from January 2010 to December 2022. We performed an interrupted time series analysis assessing trends in opioid prescribing patterns both before and after the American Academy of Pediatrics challenge. RESULTS: Of the 81,644 pediatric urology procedures, 29,595 (36.2%) received a postoperative opioid prescription, including 29.8% of circumcisions, 25.8% of hydrocelectomies, 39.6% of hypospadias repairs, 42.7% of pyeloplasties, 42.8% of ureteral reimplants. For all procedures we observed rising rates of opioid prescribing, increasing by 0.9% per 3-month interval prior to the challenge statement release from 2010 to 2018. We observed an overall significant decrease in opioid prescribing by 2.2% per 3-month interval following the challenge statement release. Additionally, since 2018, there was a significant decrease in opioid prescribing in all of the race, ethnicity, and age cohorts. CONCLUSION: Opioid prescribing following pediatric urology procedures has sharply decreased following the 2018 American Academy of Pediatrics challenge statement which underscores the value of cross-specialty quality improvement initiatives. Nonetheless, opioid prescribing remains high with potential racial or age disparities that warrant further investigation.

Long-Term Management of Problems in Cloacal Exstrophy: A Single-Institution Review.

INTRODUCTION: Cloacal exstrophy (CE) is the most severe malformation of the exstrophy-epispadias complex. This study aims to discuss long-term sequela in a single major institution with a high volume of CE patients. MATERIALS AND METHODS: A prospectively maintained database of 1490 patients on the exstrophy epispadias spectrum (145 cloacal exstrophy) from 1974 to 2023. The patient database was reviewed for CE patients >10 years of age for genitourinary, gastrointestinal, orthopedic, and psychosocial outcomes. RESULTS: A total of 63 patients (43.4%) with ≥10 years of follow up were included for analysis. Thirty-nine (61.9%) patients were 18 years or older. Twenty-two (34.9%) patients were female and 39 (61.9%) male, 14 of whom were gender converted at birth. Two female patients conceived naturally and delivered via cesarean section. No male born CE patients had biological children. Catheterizable channels were common (45/63, 71.4%) and most (88.9%) were continent. Gastrointestinal diversion was managed mostly by colostomy (37/63, 58.7%). Three out of five (60.0%) patients who underwent PSARP were continent of stool. Twenty-two (34.9%) patients were wheelchair-bound. Psychosocial diagnoses included 52.4% (33/63) patients with anxiety/depression and 27.0% with chronic pain. Out of 56 patients evaluated by physical therapy, 75% were independent in ADL performance. Of patients older than 18, 79.5% (31/39) had attended college and 82.1% (32/39) were gainfully employed. CONCLUSION: Advances in critical care, nutrition, gastrointestinal, orthopedic, and urologic management have resulted in survival rates approaching 100% among patients with CE. While these children face long-term sequela spanning various organ systems, many lead independent and fully-functional lives. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Urinary Outcomes After Magnetic Resonance Imaging-Guided Whole-Gland Transurethral Ultrasound Ablation for Prostate Cancer: Comparison of Suprapubic Tube to Indwelling Urethral Catheter.

Background: MRI-guided transurethral ultrasound ablation (TULSA) is under investigation for whole-gland ablation of low- and intermediate-risk prostate cancer. The ideal method for post-TULSA bladder drainage through postoperative suprapubic tube (SPT) vs indwelling urethral catheter (UC) has not been established. The objective of this study was to evaluate urinary outcomes after whole-gland TULSA, comparing postoperative SPT with UC. Materials and Methods: Two-institution retrospective analysis of whole-gland TULSA for men with grade group 1 and 2 prostate cancer. One institution placed SPT at the time of TULSA with clamp trials (day 10) and removal once voiding. The second placed UC until void trial (day 7). Outcomes included the International Prostate Symptom Score (IPSS), urinary bother score, catheter reinsertion, stricture, clean intermittent catheterization (CIC), and incontinence. Results: Forty-five patients (median age 67) were analyzed. The UC cohort (N = 26) was older (p = 0.007) than the SPT cohort (N = 19) but with similar baseline prostate volumes, IPSS, and urinary bother scores. Patients receiving UC had fewer days with catheter (p = 0.013). Although UC patients suffered more lower urinary tract symptoms at 1-month post-TULSA, there was no significant difference between IPSS scores at baseline and 6 months after surgery regardless of urinary management strategy, although the UC group noted significantly decreased urinary bother. Rates of infection were similar between groups. Six strictures were observed overall, with more in the SPT group, although the difference was not significant (4/19 [21.1%] SPT; 2/26 [7.7%] UC). At 6 months, incontinence rates were low and similar between groups (2/19 [10.5%] SPT; 4/26 [15.4%] UC) and only one patient (UC) required CIC. Conclusions: Our overall findings suggest that SPT and UC are both acceptable options for postoperative bladder drainage after whole-gland TULSA, with statistically similar rates of urinary complications but a slightly different side effect profile.

The use of a modified tanagho flap in the repair of posterior urethral stricture after primary exstrophy closure.

INTRODUCTION: In patients with classic bladder exstrophy (CBE), posterior urethral strictures after primary bladder closure can be difficult to manage and therefore necessitate alternative techniques in reconstruction of the proximal urethra. There is a paucity of literature describing treatment and management of posterior urethral stricture arising after repair of classic bladder exstrophy. OBJECTIVE: To describe the technique of a bladder neck reconstruction (BNR) with a modified Tanagho anterior detrusor flap in the treatment of posterior urethral stricture arising after repair of classic bladder exstrophy. PATIENTS AND METHODS: A prospectively maintained, IRB-approved database of 1401 exstrophy-epispadias patients was reviewed for patients who underwent bladder neck or proximal urethral reconstruction with modified Tanagho flap for proximal urethral stricture disease from the time period of 1975-2021. A total of 5 patients (1 female and 4 males) with classic bladder exstrophy who underwent proximal urethral reconstruction with modified Tanagho flap were identified. Of these 5 patients, the 1 female patient was treated for ongoing incontinence, not posterior urethral stricture, and was thus excluded from this report. Outcomes measured included post operative bladder capacity, post-operative continence status, upper urinary tract status, and stricture recurrence. RESULTS: Four male patients with CBE were treated for posterior urethral strictures and are reviewed here. Three patients underwent successful primary closure (1 via modern staged repair of exstrophy (MSRE) and 2 via complete primary repair of exstrophy (CPRE)), and 1 patient (MSRE) required repeat closure at the time of stricture repair. Mean age at BNR Tanagho flap was 3.8 (range 2.3-5.0) years. All patients remained stricture free with post-operative urinary incontinence; 2 patients underwent subsequent elective bladder neck transection to achieve continence. Mean follow up 9.9 (range 2.1-15.6) years. DISCUSSION: All 4 patients had excellent long term success rates, comparable to results reported in several adult studies utilizing a modified Tanagho flap in women with post-traumatic bladder neck contractures. In addition, our technique described here shares similarities with both the originally described Tanagho flap as well as with a dorsal onlay graft urethroplasty. CONCLUSION: In this limited series, modified Tanagho flap reconstruction is effective in treating posterior urethral stricture disease in CBE. This technique adds a valuable adjunct to the armamentarium of surgical options for this difficult to manage condition.

Pelvic osteotomy in cloacal exstrophy: A changing perspective.

BACKGROUND: The type of osteotomy and pelvic fixation in the management of primary cloacal exstrophy (CE) closure is variable. The purpose of this study was to evaluate primary CE closure outcomes with osteotomy, immobilization, and multi-staging procedure trends over time. METHODS: An institutional database was retrospectively reviewed for patients who underwent primary CE closure from 1960 to 2020. Demographics, osteotomy, fixation, and outcomes were noted. Subanalyses by location of primary closure (AH=author's hospital; OH=outside hospital). RESULTS: Out of 122 patients, multi-stage became more common than single-stage procedures (p = 0.019), with multi-stage associated with higher success rates (77.4% v 45.7%; p = 0.001). The use of any osteotomy increased over time (p = 0.007), with a posterior approach falling out of favor and increasing prevalence of a combined osteotomy (p<0.001). The use of any osteotomy compared to no osteotomy was associated with successful closure (77.6% v 41.7%; p = 0.007). The combined, posterior, and anterior approaches were associated with 90%, 76.2%, and 60.9% successful primary closure rates, respectively (p<0.001). Fixation modalities changed over time as Buck's traction (p<0.001) and external fixation (p<0.001) became more prevalent. Spica casting has become less common (p = 0.0002). Immobilization type was associated with success rates with Buck's (92.1%; p<0.001) and external fixation (86.0%; p<0.001) performing best. CONCLUSIONS: The use of osteotomy and fixation in the CE spectrum has changed markedly. In this cohort, a staged approach with combination osteotomy was associated with better outcomes when using a multidisciplinary team approach. LEVEL OF EVIDENCE: This is a retrospective comparative study (Type of Study: Treatment; Evidence Level: III).

Application of Tunica Vaginalis Flap for Epispadias Repair in the Epispadias-Exstrophy Complex.

OBJECTIVE: To describe long-term outcomes and experience with the tunica vaginalis flap (TVF) as a tissue augment for complex epispadias repair. METHODS: A prospectively maintained institutional database was reviewed for patients who underwent epispadias repair with TVF from 2010 to 2021. Evaluation of patient characteristics between those who developed dehiscence or UCF and those who did not was performed via Mann-Whitney U, Kruskal-Wallis, or Fisher's exact test, as appropriate. RESULTS: A total of 47 male patients were identified, of whom, 1 (2.1%) had cloacal exstrophy, 38 (80.9%) had classic bladder exstrophy or a variant, and 8 (17.0%) had epispadias as their primary exstrophy-epispadias complex diagnosis. The median age at epispadias repair was 13 months (IQR 11 - 19). The overall rate of fistula or dehiscence development was 19.1% (9 patients), of whom, 7 developed urethrocutaneous fistulae, 1 dehiscence, and 1 both. Notably, 0 of the 5 patients who had undergone prior epispadias repair and 0 of the 8 patients with a diagnosis of isolated epispadias developed a UCF or dehiscence after repair with TVF. Differences in age at repair, primary EEC diagnosis, prior epispadias repair, pre-repair testosterone, fibrin sealant utilization, closure layers, stent removal time, and bladder capacity at repair were not statistically significant (P>.05) CONCLUSION: Our expanded evaluation indicates that utilization of the tunica vaginalis as an adjunct to epispadias repair may provide durable protection against fistula development in EEC patients who have undergone prior epispadias repair and in primary repair of patients with isolated epispadias.

Postoperative Opioid Prescribing in Adolescents and Young Adults After Urologic Procedures Is Associated With New Persistent Opioid Use Disorder: A Large Claims Database Analysis.

OBJECTIVE: To assess the risk of persistent opioid use following various urologic procedures in adolescents and young adults. MATERIALS AND METHODS: The TriNetX LLC Diamond Network was queried for patients aged 13-21years who underwent pyeloplasty, hypospadias repair, inguinal hernia repair, inguinal orchiopexy, hydrocelectomy, or circumcision. Cohorts of patients prescribed and not prescribed postoperative opioids were created and propensity-matched for age, race/ethnicity, psychiatric diagnoses, and preoperative pain diagnoses. The primary outcome was new persistent opioid use, defined as new opioid use 3-9months after index procedure without another surgery requiring anesthesia during the postoperative timeframe. RESULTS: Of 32,789 patients identified, 66.0% received a postoperative opioid prescription. After propensity score matching for each procedure, 18,416 patients were included: 197 for pyeloplasty, 469 for hypospadias repair, 1818 for inguinal hernia repair, 2664 for inguinal orchiopexy, 534 for hydrocelectomy, and 3526 for circumcision. Overall, 0.41% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 1.69% of patients who received postoperative opioids developed new persistent opioid use (P < .05). Patients prescribed postoperative opioids had statistically higher odds of developing new persistent opioid use for hypospadias repair (RR: 17.0; 95% CI: 2.27-127.2), inguinal orchiopexy (RR: 3.46; 95% CI: 1.87-6.4), inguinal hernia repair (RR: 2.18; 95% CI: 1.07-4.44), and circumcision (RR: 4.83; 95% CI: 2.60-8.98). CONCLUSION: The use of postoperative opioids after urological procedures in adolescents and young adults is associated with a significant risk of developing new persistent opioid use.

Novel urinary tract obstruction marker discovery by multi-marker profiling of urinary extracellular vesicles derived from a rat UTO model.

INTRODUCTION: Congenital urinary obstruction is a common cause of end-stage renal disease in the pediatric population. However, non-invasive diagnostics to predict which patients will benefit from early intervention are lacking. METHODS: Using a rat model of upper and lower urinary tract partial obstruction and the Nanostring nCounter Fibrosis V2 Panel, we evaluated the mRNA cargo of urinary small extracellular vesicles (sEVs) and mRNA expression patterns of kidney and bladder tissues from rats with lower tract urinary obstruction and upper tract urinary obstruction. RESULTS: While mRNA hierarchical clustering of urinary sEVs was unable to differentiate upper compared to lower tract urinary obstruction, clustering was able to detect overall disease state (UUTO or LUTO) versus healthy controls. Further, urinary sEVs carried genes unique to each treatment group (UUTO: 59 genes, LUTO: 17 genes), while only one gene was uniquely carried in the control group. Notable genes of interest found in urinary sEVs were VCAM-1 and NOS1 for UUTO, Egfr for LUTO, and Pck1 for healthy controls. CONCLUSION: This study provides support that differential gene expression of urinary sEV mRNA has potential to act as biomarkers in the diagnosis and prognosis of UTO. Urinary sEVs demonstrated higher numbers of unique genes representative of injury to the kidney than that of injury to the bladder. Importantly, there were genes unique to UUTO sEVs, indicating the extent and reversibility of renal damage can be independent of the function, damage, and architecture of the bladder.

The Role of Tissue Expanders in the Reconstruction of Proximal Hypospadias.

OBJECTIVE: To report the technique and outcomes of tissue expansion (TE) for generating additional penile skin for urethroplasty and/or skin coverage during primary or redo hypospadias repair in penoscrotal transposition (PST) patients with a proximal hypospadias. METHODS: Proximal hypospadias and PST patients with a lack of penile skin, congenitally or after failed repair, who underwent TE assisted reconstruction were reviewed. TE were placed under the penile shaft and expanded skin was used for tubularized incised plate repair. Success was defined as urethral advancement to the corona or more distal with tension free skin coverage. RESULTS: A total of 24 patients underwent reconstruction including 16 as part of primary repair and for redo repairs in 8. Nine patients experienced expander extrusion and posturethroplasty complications occurred in 43.8% of primary repairs and 75.0% of redo repairs; a urethrocutaneous fistula was most common (n = 8). Overall, success was achieved in 87.5% of patients with postoperative meatal locations almost all coronal (45.8%) or glanular (50.0%). CONCLUSION: Proximal hypospadias reconstruction is challenging, and complications are not infrequent. TE is a useful alternative for complex patients with a skin paucity such that cutaneous coverage would be difficult following urethroplasty. Although the complication rate was 43.8% for primary repair, TE generated sufficient residual skin for success after additional reconstruction. For redo repair early use is most beneficial as there is more expandable skin. The pseudocapsules provide vascularized coverage to reinforce the urethra while there is sufficient skin to minimize the need for a skin graft for penile coverage.

Prevalence of opioid and benzodiazepine use in adult patients with the exstrophy-epispadias complex.

INTRODUCTION: Bladder exstrophy (BE), cloacal exstrophy (CE), and epispadias (E) are variants of the exstrophy-epispadias complex (EEC). These children require opioids and benzodiazepines to achieve pain management and immobilization for a lifetime of surgeries. It is hypothesized that these children would be sensitized to opiates and benzodiazepines as adults. The objective was to identify incidence of opiate and benzodiazepine use in adult EEC patients. METHODS: A US Health network, TriNetX Diamond was queried from 2009 to 2022. Incidence of prescriptions for benzodiazepines and opioids were calculated for adults aged 18-60 years with a diagnosis of BE, CE, or E. RESULTS: A total of 2627 patients were identified: 337 with CE, 1854 patients with BE, and 436 with E. Of these, 55.5% of CE, 56.4% of BE, and 41.1% of E had received any opioid prescription. Non-EEC controls had lower rates of opioids at 0.3%. E had a lower likelihood than BE or CE of receiving opioids (p < 0.0001, p < 0.0001). Benzodiazepines were prescribed in 30.3% of CE, 24.4% of BE, 18.3% of E, and 0.1% of controls. CE had a higher likelihood of benzodiazepines than both BE and E (p = 0.022, p < 0.001, respectively). E group had the lowest likelihood of benzodiazepine prescription (p = 0.007 when compared to BE) and all groups were significantly higher than controls (p < 0.0001 for all comparisons). For BE, females were more likely to be prescribed opioids (p = 0.039) and benzodiazepines (p = 0.027) than males. Sub-analyses revealed BE females had higher rates of surgical procedures (general, cardiac, gastrointestinal, and maternity) and chronic diagnoses (generalized anxiety disorder, major depressive disorder, chronic pain) compared to males with BE. Older age was associated with higher likelihood of opioid or benzodiazepine prescriptions in BE (p < 0.001), CE (p = 0.004), and E (p = 0.002). DISCUSSION: Across the EEC, adult patients with the most severe anomalies of CE were more likely to have received opioids and benzodiazepines. Females with BE were prescribed more opioid and benzodiazepines than males with BE. Mirroring the US population, female sex and increasing age were associated with higher rates of prescriptions, chronic diagnoses, and surgical procedures. Limitations include the lack of granular data and ability to correlate results with childhood surgeries. CONCLUSION: Adult EEC patients have higher rates of opioid and benzodiazepine prescriptions, with a high percentage of co-prescribing when compared to healthy controls. Across the spectrum, those with more severe anomalies, female sex, and increasing age were more likely to have received prescriptions.