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Background: Surgical management options for lower urinary tract symptoms due to benign prostatic hypertension have remained limited in prostates of large volume. The advent of the Aquablation has created a potential minimally invasive option for treatment in prostates of all volumes. Thus, this study aims to evaluate outcomes and complications of Aquablation in clinical practice based on prostate volume., Methods: Collected variables included adverse events with Clavien-Dindo classifications, transfusion rates, surgical retreatment rates, continued medication use postoperatively, and International Prostate Symptom Score (IPSS) with Quality-of-Life indicator. Aquablations were stratified by preoperative prostate volume., Results: One hundred seventy-four men were included in the study. The average postop decrease in IPSS was 10.28, with a 2.02 point decrease in Quality-of-Life at 1 year. Postop increase in peak urinary flow rate was 7.65 mL/s for an average of 16.44 mL/s. Hemoglobin drop average was 1.78 g/dL, but only 2.3% of patients required a transfusion. 12.9% of patients required surgical retreatment. Six months after Aquablation, 22.9% and 12.9% of patients continued taking Alpha-blockers and Androgen receptor inhibitors, respectively. Adverse events occurred in 33 patients (19.0%). Eighteen patients were excluded from secondary analysis due to unrecorded prostate volume, leaving 123 with volumes <150 mL and 33 with volumes ≥150 mL. Groups were comparable with respect to length of stay, adverse events, blood transfusion, IPSS with Quality-of-Life indicator preoperative and postoperative, postop peak urinary flow, and postop alpha-blocker use. Larger prostates had a higher rate of adverse events, retreatment, postop hemoglobin drop, and postop use of finasteride., Conclusions: Aquablation is a viable treatment option for benign prostatic hyperplasia. Efficacy, safety, subjective outcomes, and adverse event rates were not impacted by prostate volume. However, size does matter as prostates ≥150 mL had higher surgical retreatment rates and postop finasteride use., (© 2024 Wiley Periodicals LLC.)

Purpose: SARS-CoV-2 infection can result in genitourinary symptoms, such as frequency, urgency, nocturia, and pain/pressure. In this study, we followed the progression of overactive bladder (OAB) symptoms in patients that reported new or worsening OAB symptoms after coronavirus disease-19 (COVID-19) diagnosis., Materials and Methods: Individuals from a COVID-19 serology study were invited to participate in a follow-up study. Respondents were divided into three groups based on prior COVID-19 testing. Patients scored symptoms retrospectively before the pandemic, at study onset, and prospectively during 12-month follow-up. Genitourinary symptoms were assessed using international consultation on incontinence questionaire for OAB (ICIQ-OAB). Change in ICIQ-OAB scores from baseline were calculated. The minimal important difference of one on ICIQ-OAB is considered a significant change., Results: 26.0% of participants previously had positive COVID polymerase chain reaction (PCR) test (PCR+), 5.6% a positive serology test only (Ser+), and 65.5% were COVID naïve (COVID-). 23.8% of participants reported a significant increase in ICIQ-OAB score at study onset compared to prepandemic. ICIQ-OAB scores were similar at prepandemic but significantly higher at study start (p < 0.001) in PCR+ group. During follow-up, change in ICIQ-OAB scores from baseline remained unchanged for COVID- group, but gradually reduced for PCR+, reaching similar levels as COVID- group by 12 months. By 12 months, 71.4% of PCR+, 42.9% of Ser+, and 68.8% of COVID- participants still reported significant increase in ICIQ-OAB scores., Conclusions: Most COVID-19 patients experienced return of symptoms to baseline, indicative of the potential resolution of COVID-associated cystitis. A subset of cases did not, raising questions about the underlying factors contributing to this outcome. Additional research is needed to assess long COVID on urological health., (© 2024 Wiley Periodicals LLC.)

Objective: To improve diagnosis of interstitial cystitis (IC)/bladder pain syndrome(IC) we hereby developed an improved IC risk classification using machine learning algorithms., Methods: A national crowdsourcing resulted in 1264 urine samples consisting of 536 IC (513 female, 21 male, 2 unspecified), and 728 age-matched controls (318 female, 402 male, 8 unspecified) with corresponding patient-reported outcome (PRO) pain and symptom scores. In addition, 296 urine samples were collected at three academic centers: 78 IC (71 female, 7 male) and 218 controls (148 female, 68 male, 2 unspecified). Urinary cytokine biomarker levels were determined using Luminex assay. A machine learning predictive classification model, termed the Interstitial Cystitis Personalized Inflammation Symptom (IC-PIS) Score, that utilizes PRO and cytokine levels, was generated and compared to a challenger model., Results: The top-performing model using biomarker measurements and PROs (area under the curve [AUC]=0.87) was a support vector classifier, which scored better at predicting IC than PROs alone (AUC=0.83). While biomarkers alone (AUC=0.58) did not exhibit strong predictive performance, their combination with PROs produced an improved predictive effect., Conclusion: IC-PIS represents a novel classification model designed to enhance the diagnostic accuracy of IC/bladder pain syndrome by integrating PROs and urine biomarkers. The innovative approach to sample collection logistics, coupled with one of the largest crowdsourced biomarker development studies utilizing ambient shipping methods across the US, underscores the robustness and scalability of our findings., Competing Interests: Declaration of Competing Interest Laura E. Lamb – Has intellectual property associated with methods for diagnosing interstitial cystitis and is an employee/has stock options for Strata Oncology. Joseph J. Janicki – Has intellectual property associated with methods for diagnosing interstitial cystitis. Michael B. Chancellor – Has intellectual property associated with methods for diagnosing interstitial cystitis. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Percutaneous Tibial Neuromodulation (PTNM) is used to treat Overactive Bladder (OAB). This analysis summarizes patient adherence to PTNM treatment and examines trends of other third-line therapy use during and after PTNM., Methods: Optum's deidentified Clinformatics® Data Mart Database (CDM) and CMS Research Identifiable Files were queried for adults with OAB symptoms and who underwent PTNM treatment (2019-2020). We evaluated the proportion of patients who completed 12 visits within 1 year, and defined patients as treatment compliant if 12 PTNM visits were completed within 12 weeks. We then identified the proportion of patients who used other third-line therapies after PTNM and stratified these patients based on their PTNM therapy compliance status., Results: 2302 patients met selection criteria from CDM and 16,473 patients from CMS. The proportion of patients completing a full PTNM treatment course increased over time; from 16% at week 12% to 42% by week 52 (CDM) and 24% to 38% (CMS). Other third-line therapy use increased over time and was higher for PTNM noncompliant versus compliant patients at 52 weeks: onabotulinumtoxinA was 6.5% versus 5.7% for noncompliant versus compliant (CMS, p = 0.0661) and 6.4% versus 4.9% (CDM, p = 0.035), SNM trial procedure was 6.5% versus 2.5% (CDM, p = 0.002) and 4.2% versus 2.0% (CMS, p = 0.010)., Conclusions: Most patients are noncompliant with recommended PTNM treatment regimen. Albeit low, third-line therapy was pursued more frequently by noncompliant patients. Given low compliance, the effectiveness of PTNM may be compromised. Alternative implantable technologies may be needed to assure effectiveness of neuromodulation., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Pelvic cancer survivors who were treated with radiation therapy are at risk for developing (hemorrhagic) radiation cystitis (RC) many years after completion of radiation therapy. Patients with RC suffer from lower urinary tract symptoms, including frequency, nocturia, pelvic pain, and incontinence. In advanced stages, hematuria can occur, potentially escalating to life-threatening levels. Current therapeutic options for RC are limited, partly due to ethical concerns regarding bladder biopsy in patients with fragile bladder tissue. This study aimed to leverage our established preclinical model to elucidate the molecular pathways implicated in radiation-induced tissue changes in the bladder. Female C57Bl/6 mice received a single dose of 40 Gy using CT-guided imaging and a two-beam irradiation approach using the SARRP irradiator. Bladders from irradiated and age-matched littermate controls were harvested at 1 week [n = 5/group] or 6 months [n = 5/group] after irradiation, RNA was harvested, and mRNA sequencing was performed at paired-end 150bp on the Illumina NovaSeq6000 with a target of 30 million reads per sample. Following RNA sequencing, thorough bioinformatics analysis was performed using iPathwayGuide v2012 (ADVAITA Bioinformatics). Findings of the RNA sequencing were validated using qPCR analysis. At 1 week post-irradiation, altered gene expression was detected in genes involved in DNA damage response, apoptosis, and transcriptional regulation. By 6 months post-irradiation, significant changes in gene expression were observed in inflammation, collagen catabolism, and vascular health. Affected pathways included the p53, JAK-STAT, and PI3K-Akt pathways. These findings were validated in vivo in bladder tissues from our preclinical model. This is the first study to determine the molecular changes in the bladder in response to radiation treatment. We have successfully pinpointed several pathways and specific genes that undergo modification, thereby contributing to the progression of radiation cystitis. These insights enhance our understanding of the pathophysiology of radiation cystitis and may ultimately pave the way to the identification of potential new therapeutic targets.

Objective: The objective of this study was to compare maternity leave satisfaction between physicians and nonphysicians. Currently, paid maternal leave is not guaranteed in the United States, resulting in palpable dissatisfaction among parents. Previous studies have shown associations between length of paid leave and career satisfaction and maternal happiness. Materials and Methods: A Qualtrics ® electronic survey was distributed to female professionals through email and social media from April 2019 to March 2020. Inclusion criterion was ≥1 child by birth or adoption, or active pregnancy. Continuous and categorical data were analyzed using two-sample t -test and chi-square, respectively. Results: Of 808 respondents, 77% were physicians. Mean age at birth/adoption of first child was higher in physicians versus nonphysicians (32.1 years vs. 29.7 years; p  < 0.001). Physicians took shorter maternity leave than nonphysicians (10.9 weeks vs. 12.0 weeks, p  = 0.017) with half of that time paid by employers (5.4 weeks vs. 5.9 weeks, p  = 0.2). Dissatisfaction was high among physicians (85.1%) and nonphysicians (92.4%) that correlates with maternity leave compensation dissatisfaction (49% vs. 71.3%, p  < 0.001). Thirty-four percent of physicians versus 41% of nonphysicians stated that their health was negatively impacted by maternity leave length. Physicians and nonphysicians reported similar incidences of depression, and breastfeeding, delivery, and other postpartum complications. When queried, 38.8% of physicians and 57% of nonphysicians said they would desire >16 weeks of paid maternity leave ( p  < 0.001). Conclusions: In conclusion, dissatisfaction among professional women on maternity leave duration and compensation is high in the United States. Given health implications for both mother and child, this should invite further discussion and changes.

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) manifests as urinary symptoms including urgency, frequency, and pain. The IP4IC Study aimed to establish a urine-based biomarker score for diagnosing IC/BPS. To accomplish this objective, we investigated the parallels and variances between patients enrolled via physician/hospital clinics and those recruited through online crowdsourcing., Methods: Through a nationwide crowdsource effort, we collected surveys from patients with history of IC/BPS. Study participants were asked to complete the validated instruments of Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), as well as provide demographic information. We then compared the survey responses of patients recruited through crowdsourcing with those recruited from three specialized tertiary care urology clinics engaged in clinical research., Results: Survey responses of 1300 participants were collected from all 50 states of the USA via crowdsourcing and 319 from a clinical setting. ICSI and ICPI were similar for IC/BPS patients diagnosed by the physicians in clinic and self-reported by subjects via crowdsourcing stating they have a history of previous physician diagnosis of IC/BPS. Surprisingly, ICSI and ICPI were significantly lower in crowdsourced control than in-clinic control subjects., Conclusion: The IP4IC Study provides valuable insights into the similarities and differences between patients recruited through clinics and those recruited through online crowdsourcing. There were no significant differences in disease symptoms among these groups. Individuals who express an interest in digital health research and self-identify as having been previously diagnosed by physicians with IC/BPS can be regarded as reliable candidates for crowdsourcing research., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: To investigate the prevalence and cause of early discontinuation (DC) of androgen receptor inhibitor (ARi) in advanced prostate cancer (PCa) patients. Additionally, to study the effect of changing ARi vs dose reduction on duration of treatment (DOT)., Materials and Methods: A retrospective cohort study of 333 patients with advanced PCa who started ARi between 2016 and 2020 was performed. ARi medication, treatment duration, reason for DC, stage of PCa, prostate specific antigen, Gleason score, and prior PCa treatments were collected. The cohort was divided into 2 subgroups, patients that stayed on one medication (Group A) vs patients who changed ARi medication (Group B). Student's t test, chi-square test, and Kaplan-Meier survival analysis were performed., Results: At 1 year 28.8% of patient's had discontinued ARi. Reasons for DC were side effects (34.4%), death (34.4%), and cancer progression (18.8%). DOT was 13 months for enzalutamide, 13.7 months for abiraterone, 7.6 months for darolutamide, and 12.1 months for apalutamide. Average DOT for patients with a dose change was 13.4 months, similar to those without dose change at 13.9 months (P = .630). DOT was 12.7 months in Group A vs 19.8 months in Group B (P = .001)., Conclusion: In our study population DC of ARi is higher than reported in the published trials. Providing patients with an alternative ARi is associated with an increase in DOT while dose reduction is not. It is important for clinicians to understand the causes of early DC to develop strategies to maximize duration of therapy for management of advanced PCa patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Literature is sparse on COVID-19-associated cystitis (CAC), a novel condition comprising frequency, urgency, and nocturia after COVID-19 infection., Objective: To determine the incidence of CAC and correlation with SARS-CoV-2 antibody levels., Design Setting and Participants: This was a retrospective study in which urinary symptoms were scored using the International Consultation on Incontinence Questionnaire-overactive bladder (ICIQ-OAB) at three time points: before the pandemic (January 2020), 2 mo after COVID-19 infection (if applicable), and at the time of the study (May 2021). The setting was a regional health care system. The 18 785 healthcare employees who took part in the BLAST COVID study group were invited to participate, of whom 1895 responded., Outcome Measurements and Statistical Analysis: The outcome measured was the percentage of COVID-positive patients with a significant change on ICIQ-OAB over time. Pearson's χ 2 test was used for comparison of categorical data, and one-way analysis of variance for continuous data and multivariate analysis. A sample size of 618 was calculated for power of 80% and α = 0.05., Results and Limitations: Of the 1895 participants, 31.9% ( n  = 605) were positive for COVID-19 according to positive serology or a polymerase chain reaction (PCR) test. Of these, 492 were PCR-positive and had 2-mo postinfection data, with 36.4% (179/492) reporting an increase of ≥1 point on the ICIQ-OAB compared to baseline (before the pandemic), with de novo OAB in 22% of these cases (40/179). Comparison of symptoms between baseline and the study time revealed that 27.4% (31/113) of those with positive serology only (asymptomatic COVID) and 37.8% (186/492) of those with PCR positivity (symptomatic COVID) had an increase of ≥1 point on the ICIQ-OAB, compared to 15.8% ( n  = 204) of uninfected patients, with odds ratios of 2.013 (95% confidence interval [CI] 1.294-3.138; p  = 0.0015) and 3.236 (95% CI 2.548-4.080; p  < 0.0001), respectively. The retrospective nature of the study and the volunteer sample are limitations., Conclusions: COVID-19 infection increases the risk of developing new or worsening OAB symptoms., Patient Summary: We compared overactive bladder symptoms in a large group of participants between individuals with and without a previous COVID-19 infection. We found that symptomatic infection was associated with a three times greater risk of developing new or worsening overactive bladder symptoms among COVID-19 patients., (© 2022 The Author(s).)

Radiation cystitis, a long-term bladder defect due to pelvic radiation therapy, results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. The goal of this study was to identify alterations to the mechanical behavior of the urinary bladder extracellular matrix of a murine model of radiation cystitis, at 3 and 6 months after radiation exposure. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls. These findings coincided with functional bladder changes, including increased number of voids and decreased voided volume. Both mechanical and functional changes were apparent at 3 months post-irradiation and were statistically significant at 6 months, demonstrating the progressive nature of radiation cystitis. Overall, the results of this study indicate that irradiation exposure changes both the mechanical and physiological properties of the bladder. STATEMENT OF SIGNIFICANCE: In humans, radiation cystitis results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. This pathology can significantly affect recovery and quality of life for cancer survivors. Gaining knowledge about how alterations to the mechanical behavior of the urinary bladder extracellular matrix can affect urinary function will have a significant impact on this population. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls, in a mouse model of radiation cystitis. These findings were accompanied by functional voiding changes, including increased number of voids and decreased voided volume. The results of this study uncovered that irradiation exposure changes the mechanical and physiological properties of the bladder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4-8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell-cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect., (© 2021. The Author(s).)

Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch's t-test. In prostate cancer survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments., Competing Interests: The authors have declared that no competing interests exist.

There is a significant need for research and understanding of underactive bladder (UAB). The International Congress of Urologic Research and Education on Aging UnderActive Bladder (CURE-UAB) was organized by Doctors Michael Chancellor and Ananias Diokno in order to address these concerns. CURE-UAB was supported, in part, by the US National Institute of Aging and National Institute of Diabetes Digestive and Kidney. Since 2014, there have been 5 successful CURE-UAB congresses. They have brought together diverse stakeholders in the UAB field to identify areas of major scientific challenge and initiated a call to action among the medical community. In this review, we will highlight current and novel treatments under development for UAB and the progress and impact from the CURE-UAB initiative.

A subset of patients receiving radiation therapy for pelvic cancer develop radiation cystitis, a complication characterized by mucosal cell death, inflammation, hematuria, and bladder fibrosis. Radiation cystitis can reduce bladder capacity, cause incontinence, and impair voiding function so severely that patients require surgical intervention. Factors influencing onset and severity of radiation cystitis are not fully known. We tested the hypothesis that genetic background is a contributing factor. We irradiated bladders of female C57BL/6, C3H, and BALB/c mice and evaluated urinary voiding function, bladder shape, histology, collagen composition, and distribution of collagen-producing cells. We found that the genetic background profoundly affects the severity of radiation-induced bladder fibrosis and urinary voiding dysfunction. C57BL/6 mice are most susceptible and C3H mice are most resistant. Irradiated C57BL/6 mouse bladders are misshapen and express more abundant collagen I and III proteins than irradiated C3H and BALB/c bladders. We localized Col1a1 and Col3a1 mRNAs to FSP1-negative stromal cells in the bladder lamina propria and detrusor. The number of collagen I and collagen III-producing cells can predict the average voided volume of a mouse. Collectively, we show that genetic factors confer sensitivity to radiation cystitis, establish C57BL/6 mice as a sensitive preclinical model, and identify a potential role for FSP1-negative stromal cells in radiation-induced bladder fibrosis., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Objective: To determine if the vascular damage in bladders of prostate cancer (PCa) survivors with radiation cystitis can be detected through altered angiogenic growth factors in urine., Methods: Urine samples from PCa survivors with a history of external beam radiation therapy were tested for a panel of angiogenic growth factors by Luminex assay. Urine creatinine levels were measured through high performance liquid chromatography. Through a patient survey, data on patient demographics, radiation history, and urinary symptoms were collected., Results: Hepatocyte growth factor (HGF), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were altered in urine of PCa survivors with a history of radiation therapy. HGF and PlGF were elevated in response to irradiation, while VEGF had a decreasing trend. Within the irradiated population, HGF was also increased in patients diagnosed with radiation cystitis and patients with hematuria. PlGF and VEGF were only increased in the first year postirradiation, and VEGF was elevated in patients with hematuria. Finally, creatinine levels were increased in PCa survivors with a history of radiation therapy., Conclusion: Radiation cystitis is a debilitating bladder condition that cancer survivors are at risk of developing after pelvic radiation. In this study, we identified 3 pro-angiogenic factors that may be urine biomarkers and, if validated in future studies, could indicate new strategy approaches to treat radiation cystitis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Given that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options., Methods: There are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature., Results: Treatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed., Conclusions: In this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Underactive bladder (UAB) is an expanding troublesome health issue, exerting a major influence on the health and independence of older people with a disproportionally low level of attention received. The 2nd International Congress on Underactive Bladder (CURE-UAB 2) convened in Denver, CO on December 3 and 4, 2015, and comprised of top clinicians, scientists, and other stakeholders to address the challenges in UAB. A series of workshops aimed to define UAB and its phenotype, define detrusor underactivity (DU) and create a subtyping of DU, evaluate existing animal models for DU, and lastly to establish research priorities for UAB.

The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well. Unexpectedly, massive tissue swelling and edema were observed in Nrp2 -/- mice compared with wild-type littermates after delayed-type hypersensitivity reactions. Vascular permeability was twofold greater in inflamed blood vessels in Nrp2-deficient mice compared to those in Nrp2-intact littermates. The addition of exogenous SEMA3F protein inhibited vascular permeability in Balb/cJ mice, suggesting that the loss of endogenous Sema3F activity in the Nrp2-deficient mice was responsible for the enhanced vessel leakage. Functional lymphatic capillaries are necessary for draining excess fluid after inflammation; however, Nrp2-mutant mice lacked superficial lymphatic capillaries, leading to 2.5-fold greater fluid retention and severe lymphedema after inflammation. In conclusion, Nrp2 deficiency increased blood vessel permeability and decreased lymphatic vessel drainage during inflammation, highlighting the importance of the NRP2/SEMA3F pathway in the modulation of tissue swelling and resolution of postinflammatory edema., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)