Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study.

ABSTRACT: Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.

Anterior deflected urinary stream in female children: description of a unique clinical entity and surgical management.

Objectives: To investigate the clinical presentation and outcomes for a series of female pediatric patients with severe anterior deflection of the urinary stream (ADUS) who were managed via urethromeatoplasty. Methods: This single institution retrospective cohort study used the institutional billing database to identify female patients ≤18 years who received a urethromeatoplasty (CPT 53450) from 2007 to 2022. Patients were included if a substantial anterior deflection of their urinary stream was the primary indication for surgery. Patients were excluded if they were >18 years of age, had a history of prior genital trauma, or underwent surgery for an indication other than a deflected urinary stream. Results: Twenty female patients underwent urethromeatoplasty between 2007 and 2022, with a median age of 3 years old. All patients presented with difficulty aiming the urinary stream during toilet training and demonstrated a web of tissue along the posterior aspect of the urethral orifice. 19/20 patients noted immediate response (i.e., normal, non-deflected urinary stream) after the urethromeatoplasty with no further urinary complaints. There were no post-operative complications within a 90-day period. Conclusions: ADUS is a clinical entity characterized by a web of deflecting tissue at the female posterior urethral meatus that causes severe urinary deflection without other urologic symptoms. This is not well-described in the literature. Surgical correction via urethromeatoplasty is safe and effective.

Transperineal vs Transrectal Prostate Biopsy-The PREVENT Randomized Clinical Trial.

This randomized clinical trial compares the effect of transperineal vs transrectal prostate biopsy on infection rates after biopsy.

Evaluation of the efficacy of a live Escherichia coli biotherapeutic product (asymptomatic bacteriuria E. coli 212).

BACKGROUND: Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed. HYPOTHESIS/OBJECTIVE: Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs. ANIMALS: Thirty-four dogs with >1 UTI in the 12 months before presentation. METHODS: All dogs were deemed normal otherwise based on absence of abnormalities on physical examination, CBC, serum biochemical panel, and abdominal ultrasonography. Dogs were randomized to 1 of 2 treatment groups: Group 1 antimicrobials for 7 days or group 2 intravesicular administration of ASB E. coli 212. Owners were provided a voiding questionnaire regarding their dogs' clinical signs, which was completed daily for 14 days to assess clinical cure. Dogs were examined on days 7 and 14 to assess clinical cure, and urine specimens were submitted for urinalysis and bacterial culture. RESULTS: Clinical cure rates for ASB E. coli 212-treated dogs were not inferior to 7 days of antimicrobial treatment with a 12% margin of difference to determine non-inferiority. No significant difference was found between the treatment groups on days 7 and 14 in the proportion of dogs achieving ≥50% or ≥75% reduction in their clinical score compared with baseline. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that intravesicular administration of ASB E. coli 212 is not inferior to antimicrobials for the treatment of recurrent UTI in dogs. This biotherapeutic agent could help alleviate the need for antimicrobials for some dogs with recurrent UTI, improving antimicrobial stewardship.

Comparing Penile Problems in Circumcised vs. Uncircumcised Boys: Insights From a Large Commercial Claims Database With a Focus on Provider Type Performing Circumcision.

OBJECTIVES: To compare penile problems in circumcised relative to uncircumcised boys, and to determine which providers performing the circumcision have fewer post-circumcision problems. METHODS: CPT codes in the 2011-2020 MarketScan database were used to identify boys who had a circumcision. Uncircumcised control subjects of the same age, state of residence, and insurance type were selected. The primary outcome was a penile problem, defined as penis-specific infection, inflammation, and urethral stricture/stenosis, among others. The secondary outcomes were procedure-related complications limited to 28 days after circumcision, and whether post-circumcision problems varied by the clinician performing the procedure. ICD-9/10 diagnostic codes were used to identify these problems. RESULTS: We identified ∼850,000 cases and ∼850,000 matched controls. Overall, the rate of penile problems within the first five years of life was 1.7% in circumcised boys versus 0.5% in uncircumcised boys (p < 0.05). Multivariable regression models showed that the risk of penile problems was 2.9-fold higher among circumcised compared to uncircumcised males (95%CI [2.8-3], p < 0.001). Compared to males circumcised by pediatricians, those circumcised by surgeons had 2.1-fold higher penile problems in the year after circumcision (95% CI [2-2.3], p < 0.001). Procedure-related complications within 28 days of circumcision were infrequent (0.5%), with the most common being penile edema (0.2%). CONCLUSIONS: Penile problems are very infrequent in boys in the first five years of life. However, when they occur, they are 3x more likely to occur in circumcised boys relative to uncircumcised boys. Penile problems are more likely to occur in boys circumcised by surgeons. LEVELS OF EVIDENCE: Level II. TYPE OF STUDY: Prognosis study.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Inter-disciplinary provider development of an online, interactive adolescent varicocele decision aid prototype.

BACKGROUND: Decision-making regarding varicocele management can be a complex process for patients and families. However, to date, no studies have presented ways to mitigate the decisional conflict surrounding varicoceles. OBJECTIVE: To facilitate a discussion among physicians in order to develop a framework of the decision-making process regarding adolescent varicocele management, which will inform the development of the first online, interactive decision aid. MATERIALS AND METHODS: Semi-structured interviews with pediatric urologists and interventional radiologists were conducted to discuss their rationale for varicocele decision-making. Interviews were audio recorded, transcribed, and coded. Key themes were identified, grouped, and then qualitatively analyzed using thematic analysis. Utilizing the common themes identified and the Ottawa Decision Support Framework, a decision aid prototype was developed and transformed into a user-friendly website: varicoceledecisionaid.com. RESULTS: Pediatric urologists (n = 10) and interventional radiologists (n = 2) were interviewed. Key themes identified included: (1) definition/epidemiology; (2) observation as an appropriate management choice; (3) reasons to recommend repair; (4) types of repair; (5) reasons to recommend one repair over another; (6) shared decision-making; and (7) appropriate counseling. With this insight, a varicocele decision aid prototype was developed that engages patients and parents in the decision-making process. DISCUSSION AND CONCLUSIONS: This is the first interactive and easily accessible varicocele decision aid prototype developed by inter-disciplinary physicians for patients. This tool aids in decision-making surrounding varicocele surgery. It can be used before or after consultation to help families understand more about varicoceles and their repair, and why intervention may or may not be offered. It also considers a patient and family's personal values. Future studies will incorporate the patient and family perspective into the decision-making aid as well as implement and test the usability of this decision aid prototype in practice and in the wider urologic community.

Management of pediatric renal trauma - Results from the American Association for Surgery and Trauma Multi-Institutional Pediatric Acute Renal Trauma Study (Mi-PARTS).

BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).

At-home use of parasacral transcutaneous electrical nerve stimulation for pediatric voiding dysfunction: a randomized controlled trial to assess its safety and feasibility.

Introduction: Treating pediatric voiding dysfunction involves behavioral changes that require significant time or medications that are often avoided or discontinued due to side effects. Using parasacral transcutaneous electrical nerve stimulation (PTENS) has shown to have reasonable efficacy, but the safety and feasibility of its off-label use for pediatric voiding dysfunction are not well-established. Concerns have also been raised over treatment adherence. In-home therapy might improve adherence compared with office-based therapy; however, no studies have evaluated in-home feasibility to date. This study aims to assess the safety and feasibility of off-label use of PTENS for pediatric voiding dysfunction. Materials and methods: A single-institution prospective, randomized controlled study was conducted from March 2019 to March 2020. Participants aged 6-18 years diagnosed with voiding dysfunction, overactive bladder, or urinary incontinence were eligible for the study. Those with known neurologic disorders, implanted electrical devices, anatomic lower urinary tract abnormality, and recurrent urinary tract infections and those taking bladder medications were excluded. Children with primary monosymptomatic nocturnal enuresis were also excluded due to previous work suggesting a lack of efficacy. Participants were randomly assigned to receive 12 weeks of urotherapy alone (control) or urotherapy plus at-home PTENS treatment. Families were contacted weekly to assess for adverse events (AEs) and treatment adherence. The primary and secondary outcomes were safety, defined as the absence of AEs and treatment adherence, respectively. Results: A total of 30 eligible participants were divided into two groups, with 15 participants in each arm. The median age was 9.4 years (interquartile range: 7.7-10.6). In total, 60% were male. Baseline demographics and urotherapy compliance were similar between the two groups. With PTENS use, two AEs were reported, including mild pruritus at the pad site and discomfort when removing pads, while no AEs were noted in the control group. In total, 60% of patients completed three 30-min sessions per week, and all participants were able to complete treatment sessions for at least 10 weeks, involving 30 min of PTENS treatment each time. Conclusion: This randomized controlled study confirms that at-home use of PTENS is feasible with reasonable treatment adherence and minimal AEs. Future collaborative, multi-institutional studies may better determine the efficacy of this treatment modality.

Efficacy of Targeted Mast Cell Inhibition Therapy in Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

OBJECTIVE: To identify a subgroup of patients with mast cell dysfunction in chronic prostatitis/chronic pelvic pain syndrome and evaluate efficacy of mast cell-directed therapy. MATERIALS AND METHODS: Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited and evaluated in an open-label, interventional uncontrolled trial after therapy with cromolyn sodium and cetirizine hydrochloride. The primary endpoint was a change in mast cell tryptase concentrations after treatment while secondary endpoints were changes in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and AUA-SI. Isolated cells from postprostatic massage urine were evaluated for immune changes using mRNA expression analysis. RESULTS: 31 patients with a diagnoses of Category III CP/CPPS were consented, 25 patients qualified and 20 completed the study after meeting a prespecified threshold for active tryptase in expressed prostatic secretions. After treatment with cromolyn sodium and cetirizine dihydrochloride for 3-week, active tryptase concentrations were significantly reduced from 49.03±14.05 ug/mL to 25.49±5.48 ug/mL (P<.05). The NIH-CPSI total score was reduced with a mean difference of 5.2±1 along with reduction in the pain, urinary and quality of life subscores (P<.001). A reduction in the AUA-SI was observed following treatment (P<.05). NanoString mRNA analysis of isolated cells revealed downregulation of immune-related pathways including Th1 and Th17 T cell differentiation and TLR signaling. Marked reduction in CD45+ cells and specifically macrophages and neutrophil abundance was observed. CONCLUSION: Identification of CP/CPPS patients with mast cell dysfunction may be achieved using tryptase as a discriminating biomarker. Mast cell-directed therapy in this targeted subgroup may be effective in reducing symptoms and modulating the immune inflammatory environment.

Protocol of a multicentre randomised controlled trial assessing transperineal prostate biopsy to reduce infectiouscomplications.

INTRODUCTION: Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer. METHODS AND ANALYSIS: We will perform a multicentre, prospective randomised clinical trial to compare transperineal versus transrectal prostate biopsy for elevated prostate-specific antigen in the first biopsy, prior negative biopsy and active surveillance biopsy setting. Prostate MRI will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to systematic biopsy (12 cores). Approximately 1700 men will be recruited and randomised in a 1:1 ratio to transperineal versus transrectal biopsy. A streamlined design to collect data and to determine trial eligibility along with the two-stage consent process will be used to facilitate subject recruitment and retention. The primary outcome is postbiopsy infection, and secondary outcomes include other adverse events (bleeding, urinary retention), pain/discomfort/anxiety and critically, detection of non-low-grade (grade group ≥2) prostate cancer. ETHICS AND DISSEMINATION: The Institutional Review Board of the Biomedical Research Alliance of New York approved the research protocol (protocol number #18-02-365, approved 20 April 2020). The results of the trial will be presented at scientific conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04815876.

Internal hernia with volvulus after major abdominal reconstructions in pediatric urology - An infrequently reported and potentially devastating complication.

INTRODUCTION: Enterocystoplasty (EC), appendico- or ileovesicostomy (APV), and appendicocecostomy (APC) can facilitate continence and prevent renal damage for patients with congenital urologic or bowel disease. Bowel obstruction is a well-documented complication of these procedures, and the etiology of obstruction is variable. The aim of this study is to determine the incidence and describe the presentation, surgical findings, and outcomes of bowel obstruction from internal herniation due to these reconstructions. METHODS: In this single institution retrospective cohort study patients who underwent EC, APV, and/or an APC between 1/2011 and 4/2022 were identified via CPT codes within the institutional billing database. Records for any subsequent exploratory laparotomy during this same timeframe were reviewed. The primary outcome was an internal hernia of bowel into the potential space between the reconstruction and the posterior or anterior abdominal wall. RESULTS: Two hundred fifty seven index procedures were performed in 139 patients. These patients were followed for a median of 60 months (IQR 35-104 months). Nineteen patients underwent a subsequent exploratory laparotomy. The primary outcome occurred in 4 patients (including one patient who received their index procedure elsewhere) for a complication rate of 1% (3/257). The complications occurred between 19 months and 9 years after their index procedure (median 5 years). Patients presented with bowel obstruction; two patients also had sudden pain following an ACE flush. One complication was caused by small bowel and cecum passing around the APC and subsequently volvulizing. A second was caused by bowel herniating behind the EC's mesentery and the posterior abdominal wall. A third was caused by bowel herniating behind the APV mesentery and subsequently volvulizing. The exact etiology of fourth internal herniation is unknown. Of the three surviving patients, all required resection of ischemic bowel and 2 required resection of the involved reconstruction. One patient died intraoperatively from cardiac arrest. Only 1 patient required a subsequent procedure to regain lost function. CONCLUSION: Internal herniation caused by small or large bowel passing through a defect between the mesentery and abdominal wall or twisting around a channel occurred in 1% of 257 reconstructions performed over 11 years. This complication can arise many years after abdominal reconstruction, resulting in bowel resection and possibly takedown of the reconstruction. When anatomically possible and technically feasible, the surgeon should close any potential spaces created during the initial abdominal reconstruction.

Spontaneous and rapid transcanalicular translocation of a previously retractile testicle into the abdomen of a post-pubertal, teenage male.

We describe a case of spontaneous, rapid, atraumatic transcanalicular translocation of a previously retractile testis into the abdomen of a post-pubertal 16-year-old male. The testis was lowered back into the inferior scrotum laparoscopically, through a patent processus vaginalis, and was under no tension in that location without lengthening of cord structures. At 7 months postoperative, the patient reported bilateral intrascrotal testicles with no further complications. This exceptional case demonstrates that post-pubertal males with a history of retractile testis may be at risk for developing testicular translocation into the abdomen.

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Study.

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested in clinical trials. Using data from three previously published negative studies of the treatment of interstitial cystitis/ bladder pain with data on the extent of widespread pain, we examined the response of patients to different therapies base on the amount of pain beyond the pelvis. Participants with predominately local but not widespread pain responded to therapy targeting local symptoms. Participants with widespread and local pain responded to therapy targeting widespread pain. Differentiating patients with and without widespread pain phenotypes may be a key feature of designing future pain clinical trials to demonstrate treatments that are effective versus not.

Identifying variability in surgical practices and instrumentation for hypospadias repair across the Western Pediatric Urology Consortium (WPUC) network.

BACKGROUND: Although hypospadias outcomes studies typically report a level or type of repair performed, these studies often lack applicability to each surgical practice due to technical variability that is not fully delineated. An example is the tubularized incised plate (TIP) urethroplasty procedure, for which modifications have been associated with significantly decreased complication rates in single center series. However, many studies fail to report specificity in techniques utilized, thereby limiting comparison between series. OBJECTIVE: With the goal of developing a surgical atlas of hypospadias repair techniques, this study examined 1) current techniques used by surgeons in our network for recording operative notes and 2) operative technical details by surgeon for two common procedures, tubularized incised plate (TIP) distal and proximal hypospadias repairs across a multi-institutional surgical network. STUDY DESIGN: A two-part study was completed. First, a survey was distributed to the network to assess surgeon volume and methods of recording hypospadias repair operative notes. Subsequently, an operative template or a representative de-identified operative note describing a TIP and/or proximal repair with urethroplasty was obtained from participating surgeons. Each was analyzed by at least two individuals for natural language that signified specified portions of the procedure. Procedural details from each note were tabulated and confirmed with each surgeon, clarifying that the recorded findings reflected their current practice techniques and instrumentation. RESULTS: Twenty-five surgeons from 12 institutions completed the survey. The number of primary distal hypospadias repairs performed per surgeon in the past year ranged from 1-10 to >50, with 40% performing 1-20. Primary proximal hypospadias repairs performed in the past year ranged from 1-30, with 60% performing 1-10. 96% of surgeons maintain operative notes within an electronic health record. Of these, 66.7% edited a template as their primary method of note entry; 76.5% of these surgeons reported that the template captures their operative techniques very or moderately well. Operative notes or templates from 16 surgeons at 10 institutions were analyzed. In 7 proximal and 14 distal repairs, parameters for chordee correction, urethroplasty suture selection and technique, tissue utilized, and catheter selection varied widely across surgeons. CONCLUSION: Wide variability in technical surgical details of categorically similar hypospadias repairs was demonstrated across a large surgical network. Surgeon-specific modifications of commonly described procedures are common, and further evaluation of short- and long-term outcomes accounting for these technical variations is needed to determine their relative influence.

Acyloxyacyl hydrolase regulates microglia-mediated pelvic pain.

Chronic pelvic pain conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) remain clinical and mechanistic enigmas. Microglia are resident immune cells of the central nervous system (CNS) that respond to changes in the gut microbiome, and studies have linked microglial activation to acute and chronic pain in a variety of models, including pelvic pain. We have previously reported that mice deficient for the lipase acyloxyacyl hydrolase (AOAH) develop pelvic allodynia and exhibit symptoms, comorbidities, and gut dysbiosis mimicking IC/BPS. Here, we assessed the role of AOAH in microglial activation and pelvic pain. RNAseq analyses using the ARCHS4 database and confocal microscopy revealed that AOAH is highly expressed in wild type microglia but at low levels in astrocytes, suggesting a functional role for AOAH in microglia. Pharmacologic ablation of CNS microglia with PLX5622 resulted in decreased pelvic allodynia in AOAH-deficient mice and resurgence of pelvic pain upon drug washout. Skeletal analyses revealed that AOAH-deficient mice have an activated microglia morphology in the medial prefrontal cortex and paraventricular nucleus, brain regions associated with pain modulation. Because microglia express Toll-like receptors and respond to microbial components, we also examine the potential role of dysbiosis in microglial activation. Consistent with our hypothesis of microglia activation by leakage of gut microbes, we observed increased serum endotoxins in AOAH-deficient mice and increased activation of cultured BV2 microglial cells by stool of AOAH-deficient mice. Together, these findings demonstrate a role for AOAH in microglial modulation of pelvic pain and thus identify a novel therapeutic target for IC/BPS.

National Trends and Outcomes in the Use of Intravesical Botulinum Toxin and Enterocystoplasty Among Patients With Myelomeningocele.

OBJECTIVE: To compare trends in the treatment of patients with myelomeningocele receiving intravesical Botulinum (IVB) toxin and enterocystoplasty. METHODS: We identified patients with myelomeningocele in a commercial insurance database from 2008-2017 and stratified them into adult and pediatric samples. Index procedure was identified as either IVB toxin injection or enterocystoplasty. The annual rate of treatments was measured and a change in treatment rate was identified. Time to enterocysplasty was calculated using survival analysis and factors associated with clinical outcomes up to 10 years after index procedure were determined using multivariate Poisson regression. RESULTS: We identified 60,983 patients with myelomeningocele. Nearly twice as many pediatric patients had an enterocystoplasty (n = 317) compared to IVB (n = 138). Very few adult patients underwent enterocystoplasty (n = 25) compared to IVB (n = 116). We identified a significant increase in the annual rate of IVB use around mid-2010 among pediatric patients and around mid-2009 among adults. Twelve pediatric patients (8.6%) and 5 adults (4.3%) went on to receive an enterocystoplasty. Patients who received IVB as the index procedure experienced significantly lower rates of hospitalization days (RR 0.64; 95% CI 0.53-0.78), emergency department visits (RR 0.72; 95% CI 0.63-0.82), and an increased rate of urologic procedures (RR 1.44; 95% CI 1.28-1.62). CONCLUSION: The annual rate of IVB use has increased among patients with myelomeningocele. Nearly 1 in 10 pediatric patients and 1 in 20 adults go on to receive enterocystoplasty. Patients who receive IVB experience lower rates of hospitalization and emergency department visits compared to patients who receive enterocystoplasty.

46 XY undervirulized male DSD: Reporting a patient with prenatally diagnosed disorder/difference of sex development (DSD) with heterozygous LHCGR mutations.

Leydig cell hypoplasia is a rare autosomal recessive condition caused by mutations in luteinizing hormone/chorionic gonadotropin receptor (LHCGR) genes in which 46, XY patients demonstrate a wide spectrum of disorders/differences of sex development (DSD) phenotypes ranging from normal female external genitalia in severe subtypes to micropenis or hypospadias in patients with less severe presentations. Although most patients with LHCGR defects are diagnosed at puberty, here we describe the prenatal diagnosis of 46, XY DSD due to two likely pathogenic variants in LHCGR, one of which has never been reported.

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction.

Intraurethral inoculation of mice with uropathogenic Escherichia coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of a mast cell stabilizer, cromolyn sodium, and the histamine 1 receptor antagonist cetirizine di-hydrochloride in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW & NOTEWORTHY LUTS-associated benign prostatic hyperplasia is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model, suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.