Contemporary management of ischemic priapism: A 12-year population-based analysis from a large US database.

BACKGROUND: Priapism is a urological condition characterized by a persistent erection. The management varies based on its subclassifications. Despite established clinical guidelines for ischemic priapism, there is a lack of large-scale research focused on patient characteristics and management strategies. OBJECTIVES: To analyze the contemporary management of ischemic priapism in the US, exploring patient demographics and clinical characteristics, as well as predictors of erectile dysfunction (ED) and penile prosthesis implantation (PPI). MATERIALS AND METHODS: We performed a retrospective analysis of the PearlDiver Mariner database, reviewing records from 2010-2021. Adult males diagnosed with ischemic priapism were included. Data analysis covered demographic, clinical variables, and management strategies. Predictors of de novo ED and PPI were evaluated using multivariable logistic regression analysis. RESULTS: Of 36,120 patients, most (93%) received only medical management, and a minority underwent surgical interventions (penile shunt surgery [PSS], PPI or both). Medical management was typically effective, as 67.08% of the patients in this group experienced only one episode of priapism. However, de novo ED occurred in 16.57% of these patients. The majority of patients undergoing PPI had an inflatable prosthesis (81%). Older age (odds ratio, OR 1.02), the presence of metabolic diseases (OR 1.39), neurogenic disorders (OR 1.72), solid pelvic malignancies (OR 1.09), and multiple episodes of priapism were identified as significant predictors of de novo ED (all p < 0.05). Similarly, age (OR 1.03), the presence of metabolic diseases (OR 1.23), solid pelvic malignancies (OR 1.99), and multiple episodes of priapism were associated with higher likelihood of PPI (all p < 0.05). CONCLUSION: Most cases of ischemic priapism are managed with the medical therapy. Less than 3% of patients with ischemic priapism receive PPI, and when this occurs an inflatable prosthesis is favored. Age, specific comorbidities, and multiple episodes of priapism appear to be significant predictors of ED and PPI.

Current urethroplasty trends in recent GURS fellowship graduates.

PURPOSE: To assess self-reported urethroplasty success rates and outcomes of recent GURS fellowship graduates and compare these data to the large body of published urethroplasty outcomes literature. METHODS: A voluntary survey was distributed from June 1 to June 30, 2023 to GURS fellowship graduates of the last 5 years. Participants were surveyed on time since graduation, operative volume, outcomes, and quoted success rates for urethroplasty. Data were then analyzed using descriptive statistics, binary logistic regression, and correlative analyses. RESULTS: We received responses from 49/101 (48.5%) GURS graduates. Five-year post-graduates were most represented (44.7%). The majority (52.2%) consider 81-90% of urethroplasty successful, without significant change with years in practice. Approximately 65% quoted excision and primary anastomosis (EPA) as > 90% successful. Over half of the respondents had performed > 60 urethroplasties since graduation. Only 31.3% of respondents reported re-intervening in > 10% of their postop patients, with a weak positive correlation between years in practice and need for re-intervention (p 0.01). Nearly 20% of respondents referred patients to an external reconstructionist. CONCLUSION: Increased length of time in practice does not result in higher reported urethroplasty success rates, counseling on successful outcomes, or rates of re-intervention and complications. Our survey highlights that the traditionally used success rates for urethroplasty may not be reflective of new graduates and lower volume reconstructive surgeons in their early career.

Genitourinary Blastomycosis in a Young Male Patient: A Case Report and Review of Diagnostic Challenges.

Disseminated blastomycosis is an endemic fungal infection that rarely manifests with genitourinary involvement. We present a unique case of a 28-year-old professional male gamer with a remote history of hemoptysis and cervical lymphadenopathy who presented with hematospermia, lower urinary tract symptoms (LUTS), and persistent groin abscesses after left orchiectomy at an outside hospital. He underwent drainage of groin abscess and prostate biopsy for an abnormal digital rectal exam which revealed disseminated blastomycosis requiring systemic, long-term antifungal treatment. We have also included a review of literature to note clinical patterns in presentations and highlight the diagnostic challenges that this infection presents.

Colo-renal Fistula in a Patient With Refractory Anemia and Recurrent Urinary Tract Infections: A Case Report and Review of the Literature.

Although rare, colo-renal fistulas pose diagnostic challenges due to their varied presentations and etiologies. Here, we present a unique case of a woman with recurrent pyelonephritis, severe anemia, and unintended weight loss, who was eventually diagnosed with a colo-renal fistula. Delayed imaging following intraoperative fluoroscopy revealed the abnormal connection between the colon and upper urinary tract. The patient underwent nephrectomy and colon resection. This case report emphasizes the need for suspicion in diagnosing such fistulas and highlights their varied management. This case adds to the literature by illustrating an unusual presentation and underscores the complexity of diagnosis and treatment.

Depression phenotypes in spinal cord injury and impact on post-injury healthcare utilization and cost: Analysis using a large claim database.

CONTEXT/OBJECTIVE: Depression is the most common psychological comorbidity associated with spinal cord injury (SCI) and affects healthcare utilization and costs. This study aimed to use an International Classification of Disease (ICD) and prescription drug-based depression phenotypes to classify people with SCI, and to evaluate the prevalence of those phenotypes, associated risk factors, and healthcare utilization. DESIGN: Retrospective Observational Study. SETTING: Marketscan Database (2000-2019). PARTICIPANTS: Individuals with SCI were classified into six ICD-9/10, and prescription drugs defined phenotypes: Major Depressive Disorder (MDD), Other Depression (OthDep), Antidepressants for Other Psychiatric Conditions (PsychRx), Antidepressants for non-psychiatric condition (NoPsychRx), Other Non-depression Psychiatric conditions only (NonDepPsych), and No Depression (NoDep). Except for the latter, all the other groups were referred to as "depressed phenotypes". Data were screened for 24 months pre- and 24 months post-injury depression. INTERVENTIONS: None. OUTCOME MEASURES: Healthcare utilization and payments. RESULTS: There were 9,291 patients with SCI classified as follows: 16% MDD, 11% OthDep, 13% PsychRx, 13% NonPsychRx, 14% NonDepPsych, 33% NoDep. Compared with the NoDep group, the MDD group was younger (54 vs. 57 years old), predominantly female (55% vs. 42%), with Medicaid coverage (42% vs. 12%), had increased comorbidities (69% vs. 54%), had fewer traumatic injuries (51% vs. 54%) and had higher chronic 12-month pre-SCI opioid use (19% vs. 9%) (all P < 0.0001). Classification into a depressed phenotype before SCI was found to be significantly associated with depression phenotype post-SCI, as evidenced by those who experienced a negative change (37%) vs. a positive change (15%, P < 0.0001). Patients in the MDD cohort had higher healthcare utilization and associated payments at 12 and 24 months after SCI. CONCLUSION: Increasing awareness of psychiatric history and MDD risk factors may improve identifying and managing higher-risk patients with SCI, ultimately optimizing their post-injury healthcare utilization and cost. This method of classifying depression phenotypes provides a simple and practical way to obtain this information by screening through pre-injury medical records.

Corpus spongiosum flap: a unique technique in the management of urosymphyseal fistula.

Urosymphseal fistulas are a debilitating but treatable consequence of the combination of radiotherapy and endoscopic interventions in prostate cancer patients. Treatment includes fistula excision with a tissue flap to prevent communication of involved structures and provide structural and vascular support. We introduce a unique surgical approach of mobilizing and utilizing a corpus spongiosum flap in urosymphyseal fistula repair. A retrospective study identified two patients who underwent repair with a pedicled corpus spongiosum flap at our institution. The corpus spongiosum had adequate length and vascularization and limited the need for extra-pelvic muscle flaps, thus maintaining muscle integrity in the abdomen and thighs. Following extirpative surgery, both patients had durable fistula closure, decreased pelvic pain, and resolution of lower urinary tract symptoms and osteomyelitis. These cases highlight the potential of the corpus spongiosum to be a reasonable alternative interpositional flap in genitourinary reconstruction.

Health Care Utilization and Cost Associated With Urinary Tract Infections in a Privately Insured Spinal Cord Injury Population.

Background: Urinary tract infections (UTIs) are the most common secondary medical complication following spinal cord injury (SCI), significantly impacting health care resource utilization and costs. Objectives: To characterize risk factors and health care utilization costs associated with UTIs in the setting of SCI. Methods: IBM's Marketscan Database from 2000-2019 was utilized to identify individuals with traumatic SCI. Relevant ICD-9 and ICD-10 codes classified individuals into two analysis groups: having ≥ 1 UTI episode or no UTI episodes within 2 years following injury. Demographics (age, sex), insurance type, comorbidities, level of injury (cervical, thoracic, lumbar/sacral), and health care utilization/payments were evaluated. Results: Of the 6762 individuals retained, 1860 had ≥ 1 UTI with an average of three episodes (SD 2). Younger age, female sex, thoracic level of injury, noncommercial insurance, and having at least one comorbidity were associated with increased odds of UTI. Individuals with a UTI in year 1 were 11 times more likely to experience a UTI in year 2. As expected, those with a UTI had a higher rate and associated cost of hospital admission, use of outpatient services, and prescription refills. UTIs were associated with 2.48 times higher cumulated health care resource use payments over 2 years after injury. Conclusions: In addition to bladder management-related causes, several factors are associated with an increased risk of UTIs following SCI. UTI incidence substantially increases health care utilization costs. An increased understanding of UTI-associated risk factors may improve the ability to identify and manage higher risk individuals with SCI and ultimately optimize their health care utilization.

Cancer risk in bladder diverticula: a large institutional analysis of risk and management.

PURPOSE: Bladder diverticula (BD) are usually asymptomatic, but may increase the risk of infections, stones, or malignancy, likely due to urinary stasis within the BD. We aim to characterize the risk of bladder cancer (BC) within diverticula. METHODS: Retrospective review was conducted of patients diagnosed with BD between 1994 and 2021 at a single institution. Cancer risk was characterized using descriptive statistics and multivariable logistic regression as appropriate. RESULTS: We identified 764 patients with mean age 68 years, the majority of whom were male (87%) and Caucasian (86%). Of this total, 13.3% (102/764) had a diagnosis of BC and 35.3% of this subset (36/102) had definitive cancer within the BD. Diverticulectomy or partial cystectomy was performed in 13.6% (104/764), 76% of whom were preoperatively presumed to have benign disease. Surgical patients were younger and had larger BD. Of the 79 patients who underwent diverticulectomy without preoperative suspicion for cancer, 5 were incidentally diagnosed with BC on final pathology. On multivariable logistic regression, male gender [odds ratio (OR) = 2.6, p = 0.03] and increasing age (OR = 1.02, p = 0.03) were independent risk factors for BC diagnosis. Indwelling catheter, recurrent urinary tract infections (UTIs), and bladder stones did not affect the risk of BC. CONCLUSIONS: The majority of patients with BD are not managed with surgery. BC is identified in a small but considerable proportion of patients with BD, with an even lower rate of incidentally diagnosed cancer among those undergoing BD surgery. Male gender and increasing age increased the risk of BC diagnosis.

Unusual Cause of Artificial Urinary Sphincter Malfunction: Device Entanglement Resulting in Urethral Constriction and Urinary Retention.

Urinary retention following placement of an artificial urinary sphincter (AUS) is not an uncommon complication. We describe a unique case of urinary retention due to AUS entanglement causing urethral constriction in a 72-year-old male. He presented to the emergency department postoperatively following AUS placement with pelvic pain and incomplete emptying. Eventual cystourethroscopy demonstrated severe extrinsic urethral constriction despite the deactivation of the AUS device. Surgical exploration revealed an unexpected looping of the occlusive cuff, causing urethral constriction. Although the precise cause is not clearly known, we suspect that it may have been related to the process of connecting the tubing at the level of the abdomen. Regardless of the underlying etiology, this case highlights a unique complication and supports an assessment of the cuff with direct perineal inspection prior to wound closure and/or with cystourethroscopy.

Management of Urosymphyseal Fistula and Pelvic Osteomyelitis: A Comprehensive Institutional Experience and Improvements in Pain Control.

BACKGROUND: Urosymphyseal fistula (USF) is an uncommon but painful and devastating condition typically occurring after radiotherapy for pelvic malignancy, with a delayed diagnosis and a risk of opioid dependence. OBJECTIVE: To characterize our institutional experience and determine the impact of intervention for USF on pain control and opioid use. DESIGN, SETTING, AND PARTICIPANTS: We evaluated data for 33 adult patients diagnosed with USF and managed at a quaternary institution between 2009 and 2021. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed chronic opioid use, pain scores, prior therapy for pelvic malignancy, prior endoscopic procedures, microbiology and histology congruence, and postoperative complications. For comparative analyses we used a χ2 test or Fisher's exact test for categorical variables and a Wilcoxon signed-rank test for continuous variables. RESULTS AND LIMITATIONS: Nearly 94% of the patients had received prior pelvic radiotherapy and >80% occurred in 2016-2021 but were not diagnosed until a median of 10 mo (interquartile range [IQR] 3.5-19.5) following endoscopic procedure(s). Osteomyelitis was suspected in 78.8% of imaging reports and nearly 70% had a positive preoperative urine culture. Over 90% of patients underwent cystectomy, pubic bone debridement or resection, and a soft-tissue pedicle flap. Preoperative urine cultures were concordant with 60% of intraoperative tissue/bone cultures. Histologic osteomyelitis was identified in 85% and concordant with 80% of preoperative imaging. Clavien-Dindo grade ≥3 complications occurred in 15.6%. The median pain score decreased from 4 (IQR 0-8) preoperatively to 0 (IQR 0) postoperatively (p < 0.001). Chronic opioid use decreased from 39.4% to 21.2% (p = 0.02). CONCLUSIONS: Pelvic osteomyelitis may complicate USF and commonly manifests with severe, persistent pain. USF incidence may be increasing or at least increasingly recognized, but diagnosis is delayed. Definitive management results in significant improvements in pain perception and a decrease in chronic opioid use. PATIENT SUMMARY: We examined features of urinary fistulas, which are abnormal openings or connections between part of the urinary tract and another structure. Patients with a urinary fistula involving the pelvic bones can present with severe pain, but diagnosis of the condition is often delayed. Removal of some pelvic bone with bladder removal or repair can result in a decrease in long-term pain and in the use of opioid drugs for pain relief.

External validation of the priapism impact profile in a Jamaican cohort of patients with sickle cell disease.

BACKGROUND: Priapism impairs quality of life and has a predilection for males with sickle cell disease (SCD). The Priapism Impact Profile (PIP) is a novel 12-item instrument designed to measure general health-related impact of priapism. The aim of the study was to evaluate the validity and reliability of the PIP in a Jamaican cohort of SCD patients experiencing priapism. METHODS: One hundred SCD patients with a history of priapism were recruited from a sickle cell clinic in Kingston, Jamaica and administered the PIP questionnaire. Patients rated each item of the PIP for clarity and importance. Statistical testing was employed to evaluate the psychometric performance of the PIP. Content validation was assessed based on patient descriptive rating of the items based on clarity, and importance and criterion-oriented validity were assessed by evaluating the PIP's ability to distinguish between patient subgroups. Test-retest repeatability was assessed in 20 of the 100 patients. RESULTS: Patients were stratified into active (54) and remission (46) priapism groups based on their experience of priapism within the past year. Patients in the active priapism group were younger (p = 0.011), had a shorter duration of disease (p = 0.023), and had more frequent priapism episodes (p = 0.036) than the remission group. PIP questionnaire scores differed significantly with respect to priapism activity (p < 0.001) and prevalence of erectile dysfunction (p < 0.05) but not by priapism severity (p = 0.62). The PIP questionnaire had good content validity, with questions rated as having medium or high clarity and importance by an average of 82.8% and 69.2% of patients, respectively. CONCLUSION: The PIP questionnaire was successfully validated in a Jamaican cohort of SCD patients and adequately discriminated patients with active priapism from those in remission. The instrument may be utilized in routine clinical management of patients with SCD-associated priapism. Further clinical investigations are warranted in other populations.

Urosymphyseal fistulas in women: identification and characterization of a previously undescribed phenomenon.

Urosymphyseal fistula (USF) is a very uncommon but catastrophic condition which typically occurs in the setting of previous radiation treatment for prostate cancer. As a result, USF has only been described in male populations. For the first time, we characterize this phenomenon in a series consisting of four women managed at our quaternary institution. We found that most patients presented with pubic pain and all were diagnosed with USF on CT or MRI. Imaging commonly demonstrated features suggesting osteomyelitis which was confirmed on histology. Patients experienced significant decreases in peri-operative pain scores following extirpative surgery with urinary diversion, bone debridement/resection and tissue interposition. This case series highlights the rarity of USF in women in order to help promote increased recognition and timely management.

Outcomes of Robot-assisted Partial Nephrectomy for Clinical T3a Renal Masses: A Multicenter Analysis.

BACKGROUND: Use of partial nephrectomy (PN) in T3 renal cell carcinoma (RCC) is controversial. OBJECTIVE: To evaluate quality outcomes of robot-assisted PN (RAPN) for clinical T3a renal masses (cT3aRM). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter analysis of patients with cT3aN0M0 RCC who underwent RAPN. INTERVENTION: RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was a trifecta composite outcome of negative surgical margins, warm ischemia time (WIT) ≤25 min, and no perioperative complications. The optimal outcome was defined as achieving this trifecta and ≥90% preservation of the estimated glomerular filtration rate (eGFR) and no stage upgrading of chronic kidney disease. Multivariable analysis (MVA) identified risk factors associated with lack of the optimal outcome. Kaplan-Meier analysis was conducted for survival outcomes. RESULTS AND LIMITATIONS: Analysis was conducted for 157 patients (median follow-up 26 mo). The median tumor size was 7.0 cm (interquartile range [IQR] 5.0-7.8) and the median RENAL score was 9 (IQR 8-10). Median estimated blood loss (EBL) was 242 ml (IQR 121-354) and the median WIT was 19 min (IQR 15-25). A total of 150 patients (95.5%) had negative margins. Complications were noted in 25 patients (15.9%), with 4.5% having Clavien grade 3-5 complications. The median change in eGFR was 7 ml/min/1.72 m2, with ≥90% eGFR preservation in 55.4%. The trifecta outcome was achieved for 64.3% and the optimal outcome for 37.6% of the patients. MVA revealed that greater age (odds ratio [OR] 1.06; p = 0.002), increasing RENAL score (OR 1.30; p = 0.035), and EBL >300 ml (OR 5.96, p = 0.006) were predictive of failure to achieve optimal outcome. The 5-yr recurrence-free survival, cancer-specific survival, and overall survival, were 82.1%, 93.3%, and 91.3%, respectively. Limitations include the retrospective design. CONCLUSIONS: RAPN for select cT3a renal masses is feasible and safe, with acceptable quality outcomes. Further investigation is requisite to delineate the role of RAPN in cT3a RCC. PATIENT SUMMARY: Robot-assisted partial nephrectomy in patients with stage 3a kidney cancer provided acceptable survival, functional, and morbidity outcomes in the hands of experienced surgeons, and may be considered as an option when clinically indicated.

Effect of Obesity and Overweight Status on Complications and Survival After Minimally Invasive Kidney Surgery in Patients with Clinical T2-4 Renal Masses.

Objective: To evaluate the effect of obesity and overweight on surgical, functional, and survival outcomes in patients with large kidney masses after minimally invasive surgery. Materials and Methods: Within a multicenter multinational dataset, patients found to have ≥cT2 renal mass and treated with minimally invasive (laparoscopic or robotic) kidney surgery (radical or partial nephrectomy) during the period 2003 to 2017 were abstracted. They were stratified according to the body mass index classes as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Mixed models and Cox proportional hazard regression tested differences in complication rates, estimated glomerular filtration rate (eGFR) change over time, overall mortality (OM), and disease recurrence (DR) rates. Results: Of 812 patients, 30.6% were normal weight, 42.7% were overweight, and 26.7% obese. Overweight (odds ratio 0.82, 95% confidence interval [CI]: 0.51-1.31, p = 0.406) and obese patients (OR: 0.81, 95% CI: 0.44-1.47, p = 0.490) experienced similar complication rates than normal weight. Moreover, no statistically significant differences in eGFR were found for overweight (p = 0.129) or obese (p = 0.166) patients compared to normal weight. However, higher OM rates were recorded in overweight (hazard ratio [HR] 3.59, 95% CI: 1.03-12.51, p = 0.044), as well as in obese, patients (HR 7.83, 95% CI: 2.20-27.83, p = 0.002). Similarly, higher DR rates were recorded in obese (HR 2.76, 95% CI: 1.40-5.44, p = 0.003) patients. Conclusions: Obese and overweight patients do not experience higher complication rates or worse eGFR after minimally invasive kidney surgery, which therefore can be deemed feasible and safe also in this subset of patients. Nevertheless, obese and overweight patients seem to carry a higher risk of OM, and therefore, they should undergo a strict follow-up after surgery.

Robotic partial nephrectomy versus radical nephrectomy in elderly patients with large renal masses.

BACKGROUND: Recent evidence suggests that the "oldest old" patients might benefit of partial nephrectomy (PN), but decision-making for this subset of patients is still controversial. Aim of this study is to compare outcomes of robotic partial (RPN) or radical nephrectomy (RRN) for large renal masses in patients older than 65 years. METHODS: We identified 417≥65 years old patients who underwent RRN or RPN for cT1b or ≥cT2 renal mass at 17 high volume centers. Propensity score match analysis was performed adjusting for age, ASA≥3, pre-operative eGFR, and clinical tumor size. Predictors of complications, functional and oncological outcomes were evaluated in multivariable logistic and Cox regression models. RESULTS: After propensity score analysis, 73 patients in the RPN group were matched with 74 in the RRN group. R.E.N.A.L. Score (9.6±1.7 vs. 8.6±1.7; P<0.001), and high complexity (56 vs. 15%; P=0.001) were higher in the RRN. Estimated blood loss was higher in the RPN group (200 vs. 100 mL; P<0.001). RPN showed higher rate of overall complications (38 vs. 23%; P=0.05), but not major complications (P=0.678). At last follow-up, RPN group showed better functional outcomes both in eGFR (55.4±22.6 vs. 45.7±15.7 mL/min; P=0.016) and lower eGFR variation (9.7 vs. 23.0 mL/min; P<0.001). The procedure type was not associated with recurrence free survival (RFS) (HR: 0.47; P=0.152) and overall mortality (OM) (0.22; P=0.084). CONCLUSIONS: RPN in elderly patients with large renal masses provides acceptable surgical, and oncological outcomes allowing better functional preservation relative to RRN. The decision to undergo RPN in this subset of patients should be tailored on a case by case basis.

Dysregulated NO/PDE5 signaling in the sickle cell mouse lower urinary tract: Reversal by oral nitrate therapy.

AIMS: Nitric oxide (NO) has a critical, but not well understood, influence in the physiology of the lower urinary tract. We evaluated the effect of NO/phosphodiesterase (PDE)5 signaling in voiding dysfunction in the sickle cell disease (SCD) mouse, characterized by low NO bioavailability. MAIN METHODS: Adult SCD (Sickle) and wild-type (WT) male mice were treated daily with sodium nitrate (10 mM) or vehicle. After 18 days, blood was obtained for nitrite measurement, urethra was collected for organ bath study, and bladder and urethra were collected for Western blot analysis of PDE5 phosphorylation (Ser-92) (activated form). Non-anesthetized mice underwent evaluation of urine volume by void spot assay. eNOS phosphorylation (Ser-1177) and nNOS phosphorylation (Ser-1412) (positive regulatory sites) were evaluated in the bladder and urethra of untreated mice. KEY FINDINGS: Sickle mice exhibited decreased eNOS, nNOS, and PDE5 phosphorylation in the bladder and urethra, decreased plasma nitrite levels, increased relaxation of phenylephrine-contracted urethral tissue to an NO donor sodium nitroprusside, and increased total urine volume, compared with WT mice. Nitrate treatment normalized plasma nitrite levels, relaxation of urethra to sodium nitroprusside, PDE5 phosphorylation in the urethra and bladder, and urine volume in Sickle mice. SIGNIFICANCE: Derangement in PDE5 activity associated with basally low NO bioavailability in the bladder and urethra contributes to the molecular basis for voiding abnormalities in Sickle mice. Inorganic nitrate supplementation normalized voiding in Sickle mice through mechanisms likely involving upregulation of PDE5 activity. These findings suggest that interventions targeting dysregulatory NO/PDE5 signaling may ameliorate overactive bladder in SCD.

Urinary dysfunction in transgenic sickle cell mice: model of idiopathic overactive bladder syndrome.

Voiding abnormalities are common among the sickle cell disease (SCD) population, among which overactive bladder (OAB) syndrome is observed at rates as high as 39%. Although detrusor overactivity is the most common cause of OAB, its molecular pathophysiology is not well elucidated. The nitric oxide (NO) signaling pathway has been implicated in the regulation of lower genitourinary tract function. In the present study, we evaluated the role of the NO signaling pathway in voiding function of transgenic SCD mice compared with combined endothelial and neuronal NO synthase gene-deficient mice, both serving as models of NO deficiency. Mice underwent void spot assay and cystometry, and bladder and urethral specimens were studied using in vitro tissue myography. Both mouse models exhibited increased void volumes; increased nonvoiding and voiding contraction frequencies; decreased bladder compliance; increased detrusor smooth muscle contraction responses to electrical field stimulation, KCl, and carbachol; and increased urethral smooth muscle relaxation responses to sodium nitroprusside compared with WT mice. In conclusion, our comprehensive behavioral and functional study of the SCD mouse lower genitourinary tract, in correlation with that of the NO-deficient mouse, reveals NO effector actions in voiding function and suggests that NO signaling derangements are associated with an OAB phenotype. These findings may allow further study of molecular targets for the characterization and evaluation of OAB.