Who Progresses to Third-Line Therapies for Overactive Bladder? Trends From the AQUA Registry.

INTRODUCTION: Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS: Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS: A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and ß3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS: Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

Factors Influencing Medication Selection for Management of Overactive Bladder: Trends and Insights From AUA Quality Registry.

OBJECTIVE: To determine how a patient's demographics, including insurance type, race/ethnicity, gender, and age, may impact the choice of medication prescribed for overactive bladder (OAB). METHODS: We queried the AUA Quality Registry for adults between 2014 and 2020 with a diagnosis of OAB for >1year, excluding neurogenic causes. Variables included age, race/ethnicity, gender, insurance type, medication first prescribed, year of prescription, provider metropolitan status, and provider practice type. Primary outcome was which factors were associated with increased odds of beta-3 prescription as first medication choice. RESULTS: We found 1,453,566 patients with OAB, 641,122 (44.1%) with complete data. Of these, 112,021 (17.5%) were prescribed medication. On multivariate analysis, patients with Medicaid, Medicare, and other/self-pay insurance were less likely to receive a beta-3 vs an anticholinergic compared to private or military insurance. Compared to white patients, Asian, Black, and other races were less likely to receive a beta-3, as were patients outside of metropolitan areas. Age >50, prescriptions after 2014, and nonacademic settings were associated with increased odds of beta-3 prescription. There was no difference between genders. CONCLUSION: Many nonclinical factors, including insurance type and race, may affect which medication is first prescribed for OAB. This is useful for practicing urologists and may help lower barriers to beta-3 prescription through policy change and advocacy.

The Role of Frailty on Surgical Outcomes Following Pelvic Organ Prolapse Surgery in Medicare Beneficiaries: A National Study.

OBJECTIVE: To evaluate the association of frailty with surgical outcomes following pelvic organ prolapse (POP) surgery in Medicare beneficiaries. METHODS: This is a retrospective cohort study of female Medicare beneficiaries ≥65 years of age undergoing POP surgery between 2014 and 2016. Primary outcomes were hospital length-of-stay (LOS) ≥3 days, 30-day post-operative complications (excluding urinary tract infections (UTI)), and 30-day UTI. Frailty was quantified using the validated Claims-Based Frailty Index (CFI) and categorized into not frail (CFI<0.15), pre-frail (0.15≤CFI<0.25), mildly frail (0.25≤CFI<0.35), and moderately to severely frail (0.35≤CFI≤1). RESULTS: Among the 107,890 women included (mean age, 73.3±6 years), 91.3% were White as and 4.3% were classified as mildly or moderately to severely frail. Rates of hospital LOS≥3 days and 30-day UTI increased over 7-fold and rates of 30-day complications increased over 3-fold as CFI increased from not frail to moderately to severely frail (all P values <.001). Compared to women who were not frail, women who were moderately to severely frail demonstrated an increased relative risk of hospital LOS≥3 days (aRR 3.1 [95% CI 2.5-3.8,P <.001]), 30-day complications (aRR 2.8 [95% CI 2.2-3.6, P <.001]), and 30-day UTI (aRR 2.5 [95% CI 2.2-3.0, P <.001]). CONCLUSION: Among Medicare beneficiaries undergoing POP surgery in the United States, frailty is strongly associated with increased risk of prolonged hospital stay and 30-day complications. Frailty should be considered in the preoperative assessment for POP surgeries to improve patient outcomes.

Microenergy acoustic pulse therapy restores function and structure of pelvic floor muscles after simulated birth injury.

Background: The mechanisms of the microenergy acoustic pulse (MAP) therapy on restoring structure and function of pelvic floor muscles (PFM) after simulated birth injury are not well understood. Methods: A total 24 female Sprague-Dawley rats were randomly grouped into sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN, an irreversible LOX inhibitor), and VBDO + BAPN and treated with MAP (n=6 in each group). The MAP therapy was administered 2 times per week for 4 weeks with 1-week washout, the functional and histological studies were conducted in all 24 rats. The viscoelastic behavior of the PFM, including iliococcygeus (IC) and pubococcygeus (PC), was examined with a biomechanical assay. The structure of the PFM was assessed by immunofluorescence and Masson's trichrome staining. Results: The leak point pressure (LPP) assay demonstrated that the MAP therapy group had higher LPPs compared to that of VBDO and BAPN groups. In the sham group, the muscular stiffness (K) of IC muscle was significantly higher than that of PC muscle while the pelvic floor muscle rebound activity (MRA) of PC muscle was stronger than that of IC muscle (291.26±45.33 and 241.18±14.23 N/cm2, respectively). Both VBDO and BAPN decreased the MRA and increased the K in both IC and PC. Histologic examination revealed increased fibrous tissue (collagen) and degeneration of muscle fibers in both VBDO and BAPN groups. MAP therapy significantly reduced the collagen content and improved the architecture of muscle fibers. Conclusions: MAP appears to restore the structure and function of PFM by regenerating muscular fibers and improving biomechanical properties in an animal model of simulated birth injury.

Frailty Is Associated with an Increased Risk of Complications and Need for Repeat Procedures after Sling Surgery in Older Adults.

PURPOSE: Sling surgery is the gold standard treatment for stress urinary incontinence in women. While data support the use of sling surgery in younger and middle-aged women, outcomes in older, frail women are largely unknown. MATERIALS AND METHODS: Data were examined for all Medicare beneficiaries ≥65 years old who underwent sling surgery with or without concomitant prolapse repair from 2014 to 2016. Beneficiaries were stratified using the Claims-Based Frailty Index (CFI) into 4 categories: not frail (CFI <0.15), prefrail (0.15 ≤CFI <0.25), mildly frail (0.25 ≤CFI <0.35) and moderately to severely frail (CFI ≥0.35). Outcomes included rates and relative risk of 30-day complications, 1-year mortality and repeat procedures for persistent incontinence or obstructed voiding at 1 year. RESULTS: A total of 54,112 women underwent sling surgery during the study period, 5.2% of whom were mildly to moderately to severely frail. Compared to the not frail group, moderately to severely frail beneficiaries demonstrated an increased adjusted relative risk (aRR) of 30-day complications (56.5%; aRR 2.5, 95% CI: 2.2-2.9) and 1-year mortality (10.5%; aRR 6.7, 95% CI: 4.0-11.2). Additionally, there were higher rates of repeat procedures in mildly to severely frail beneficiaries (6.6%; aRR 1.4, 95% CI: 1.2-1.6) compared to beneficiaries who were not frail. CONCLUSIONS: As frailty increased, there was an increased relative risk of 30-day complications, 1-year mortality and need for repeat procedures for persistent incontinence or obstructed voiding at 1 year. While there were fewer sling surgeries in performed frail women, the observed increase in complication rates was significant. Frailty should be strongly considered before pursuing sling surgery in older women.

Sensation of incomplete bladder emptying in women: Lack of correlation to an elevated post-void residual.

INTRODUCTION/BACKGROUND: Sensation of incomplete bladder emptying (SIBE) has been shown to be correlated with an elevated post-void residual (PVR) in men, however, the significance of this symptom and whether it correlates with an elevated PVR in women is less clear. In this study, we assessed if SIBE in women is correlated with an elevated PVR and determined the relationship of SIBE to other lower urinary tract symptoms. METHODS/MATERIALS: Women ages ≥18 with lower urinary tract symptoms were eligible. SIBE was defined by a response "sometimes", "most of the time", or "all of the time" to the question "How often do you feel that your bladder has not emptied properly after you have urinated?" on the International Consultation on Incontinence Questionnaire. Frequency and bother of other lower urinary tract symptoms were also assessed to compare their relationship to SIBE. Elevated PVR was defined as ≥100 ml via ultrasound. RESULTS: We prospectively evaluated 95 women, 59% of whom reported SIBE. Compared to women without SIBE, women with SIBE reported more urinary hesitancy (51% vs. 18%, p = 0.002), intermittency (56% vs. 16%, p < 0.001), weak stream (36% vs. 5%, p < 0.001), dysuria (29% vs. 5%, p = 0.004), and straining (25% vs 5%, p = 0.013). However, there was no difference in elevated PVRs between women with and without SIBE [5/56, 9% vs. 4/39, 10%, (p = 0.99)]. All women, regardless of SIBE, reported higher bother from storage and incontinence symptoms versus voiding symptoms with no difference in overall bother scores. CONCLUSION: SIBE is a common complaint in women with lower urinary tract symptoms. While women with SIBE reported more voiding symptoms, they were more bothered by storage symptoms. Importantly, most of these women emptied their bladder well and were not more likely to have an elevated PVR than women without SIBE.

African American Men have Increased Risk of Prostate Cancer Detection Despite Similar Rates of Anterior Prostatic Lesions and PI-RADS Grade on Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To determine whether the frequency of anterior prostate lesions (APL) on multiparametric magnetic resonance imaging (mpMRI) prior to biopsy differed between African American (AA) and non-AA men and evaluate implications of race and tumor location for prostate cancer (PCa) detection. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015-December 2020) without prior diagnosis of PCa were evaluated for APLs by race. Multivariable logistic regression models evaluated predictors of APLs and associations of APLs and race with detection of any PCa (grade group 1+) and clinically significant PCa (csPCa; grade group 2+). Additional stratified and propensity score matched analyses were conducted. RESULTS: Of 1,239 men included, 190 (15.3%) were AA and 302 (24.4%) had at least one APL with no differences by race on multivariable analysis. While men with APLs were twice as likely to harbor PCa or csPCa, the unadjusted proportion of targeted biopsy-confirmed APL PCa (12.6% vs 12.0%) or csPCa (8.4% vs 8.9%) were similar for AA and non-AA men. AA men had higher risk of prostate cancer on targeted cores (OR 1.66 (95%CI 1.06 - 2.61), P = 0.026) which was independent of lesion location or PI-RADS. CONCLUSION: AA men were found to have similar rates of APLs on mpMRI to non-AA men indicating access to mpMRI may mitigate some of the historical racial disparity based on lesion location. AA men have increased risk of PCa detection compared to non-AA men independent of anterior location or lesion grade on mpMRI reinforcing the importance of identifying genetic, biologic, and socioeconomic drivers.

The microbiome of calcium-based urinary stones.

Historically, the role of bacteria in urinary stone disease (USD) has been limited to urease-producing bacteria associated with struvite stone formation. However, growing evidence has revealed bacteria associated with stones of non-struvite composition. These bacteria may be derived from either urine or from the stones themselves. Using 16S rRNA gene sequencing and an enhanced culture technique (EQUC), we identified the urine and stone microbiota of USD patients and then determined if bacteria were statistically enriched in the stones relative to the urine. From 52 patients, bladder urine and urinary stones were collected intraoperatively during ureteroscopy. Stone homogenate and urine specimens were subjected to 16S rRNA gene sequencing and EQUC. Standard Chi-squared tests were applied to determine if the relative abundance of any bacterial taxon was significantly enriched in urinary stones compared to urine. Stones were primarily calcium-based. 29/52 (55.8%) stones had bacteria detected by 16S rRNA gene sequencing. Of these, dominant bacterial taxa were enriched from 12 stones. Bacterial taxa isolated by EQUC include members of the genera Staphylococcus, Enterobacter, Escherichia, Corynebacterium, and Lactobacillus. Dominant bacterial genera were enriched compared to paired bladder urine. Differences between the stone and urine microbiota may indicate that certain bacteria contribute to USD pathophysiology. Further investigation is warranted.

Impact of preoperative urodynamics on women undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: Preoperative urodynamic studies (UDS) are frequently performed before pelvic organ prolapse (POP) surgery to assess urethral and bladder function. The primary goal of this study is to examine how preoperative UDS are utilized and what value these studies have in patient treatment and/or counseling. METHODS: We retrospectively reviewed patients who underwent prolapse surgery and had preoperative UDS between June 2010 and February 2015. Indications for UDS were classified into four categories: (1) occult stress urinary incontinence only, (2) overactive bladder symptoms, (3) mixed or insensible urinary incontinence, and (4) voiding symptoms and/or elevated post-void residual. We identified changes in management or counseling that were directly attributable to UDS results prior to surgery. RESULTS: Three hundred ninety-two patients underwent urodynamic testing for indications 2-4 above, and 316 met the inclusion criteria. Fifty-seven percent (180/316) had OAB symptoms (34.4% wet, 65.6% dry), 40.2% (127/316) had mixed incontinence, and 17.1% (54/316) had voiding symptoms and/or elevated PVR. A total of 3.5% (11/316) patients had alteration in their management or counseling based on the results of the UDS; 29.4% (50/170) of the women evaluated for occult SUI alone or with other symptoms demonstrated it and 41 underwent sling placement. CONCLUSIONS: UDS did not have a significant impact on preoperative management or counseling in POP surgery if demonstration of occult SUI was not the indication for preoperative study in women committed to POP surgery. Major alterations in treatment were rare and occurred mostly in women with stress incontinence that also had concomitant voiding symptoms and/or elevated PVR.

Male Bladder Microbiome Relates to Lower Urinary Tract Symptoms.

BACKGROUND: In women, compelling evidence associates lower urinary tract microbiota (LUTM) with lower urinary tract symptoms (LUTS); a similar association in men with benign prostate enlargement (BPE) is not established. OBJECTIVE: To determine whether associations exist between LUTM and LUTS. DESIGN, SETTING, AND PARTICIPANTS: Forty-nine male volunteers, aged 40-85 yr, were recruited from one academic tertiary care center. Twenty-eight patients undergoing BPE/LUTS surgery and 21 undergoing non-BPE/LUTS surgery were stratified by International Prostate Symptom Score (IPSS), and paired voided/catheterized urine specimens were collected for expanded quantitative urine culture (EQUC) and 16S ribosomal RNA gene sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary and secondary outcomes were presence of detectable LUTM and specific bacterial members of the LUTM, respectively. Baseline data were compared. Univariable logistic regression models were used to calculate odds ratios (ORs) for IPSS category associated with the presence of bladder microbiota. Relative LUTM proportions were compared with IPSS using chi-square tests. RESULTS AND LIMITATIONS: Thirty-nine percent of catheterized and 98% of voided specimens contained LUTM. Catheterized and voided LUTM differed significantly. LUTM was detected in catheterized urine of 22.2% of men with mild LUTS, 30.0% with moderate LUTS, and 57.1% with severe LUTS (p=0.024). Increased IPSS category was associated with significantly higher odds of detectable bacteria (OR: 2.21, 95% confidence interval: 1.09-4.49). Small sample size limited this study, making it unable to identify significant differences in specific bacterial taxa based on IPSS. CONCLUSIONS: Voided urine does not adequately characterize the male bladder microbiome. In males with and without BPE, IPSS severity was associated with detectable bacteria in catheterized urine, which samples the bladder. Additional studies are needed to identify specific bladder bacteria associated with LUTS. PATIENT SUMMARY: To study bladder bacteria, urine should be collected with a catheter. Men with severe urinary symptoms are more likely to have detectable bladder bacteria than those with less severe symptoms.

Vaginal Dehiscence and Evisceration After Robotic-assisted Radical Cystectomy: A Case Series and Review of the Literature.

OBJECTIVE: To describe a rare complication in 5 women who had vaginal prolapse, dehiscence, and/or evisceration after having undergone robotic-assisted radical cystectomy with creation of ileal conduit urinary diversion. Radical cystectomy is the standard of care in the extirpative treatment for muscle invasive urothelial carcinoma. Anterior exenteration in the female patient requires removal of the anterior vaginal wall, urethra, uterus, and adnexa which results in significant changes to the pelvic floor. METHODS: Retrospective identification of all women having undergone robotic-assisted radical cystectomy for urothelial carcinoma who ultimately represented with vaginal prolapse, dehiscence, and/or evisceration between January 2012 and April 2019. We identified patient characteristics detailing their presentation. A review of the available literature highlighted the lack of available information in this uncommon cohort. RESULTS: Five women with vaginal dehiscence and/or evisceration who had previously undergone robotic-assisted radical cystectomy, anterior vaginectomy with urethrectomy, pelvic lymph node dissection, and creation of ileal conduit by 4 surgeons were identified. Mean interval time to initial presentation of prolapse or dehiscence was 44.4 weeks (range 11-120). In the 2 patients that eviscerated prior to repair, this occurred at 5 and 25 weeks after initial outpatient consultation. All reconstructive efforts were approached transvaginally. Two patients underwent 2 or more repairs. Management options included expectant management, pessary, and immediate vs delayed transvaginal surgical repair. CONCLUSION: Our case series describes the unique and potentially devastating complication of vaginal dehiscence and bowel evisceration in women with history of robotic-assisted radical cystectomy.

Role of Multiparametric Magnetic Resonance Imaging Prostate Specific Antigen Density and PI-RADS™ Score in Predicting Up Staging in Men on Active Surveillance.

INTRODUCTION: Using a combination of magnetic resonance imaging of the prostate and prostate specific antigen density, we determined which men on active surveillance are at risk for up staging and which men could avoid repeat biopsy while remaining on surveillance. METHODS: We reviewed the records of 110 men on active surveillance with Gleason 6 disease who underwent magnetic resonance imaging followed by UroNav fusion biopsy (Invivo, Gainesville, Florida). Using univariable and multivariable logistic regression analyses we examined the effect of age, race, prostate specific antigen, prostate specific antigen density, prostate volume, PI-RADS (Prostate Imaging Reporting and Data System) score, number and size of target lesions, and time on surveillance to determine the likelihood of up staging to Gleason 7 or greater disease. RESULTS: A total of 33 cases (30%) were up staged. On multivariable analysis prostate specific antigen density and PI-RADS score were significant predictors of up staging with adjusted odds ratios of 3.97 for prostate specific antigen density of 0.16 or more (CI 1.31-12.00, p <0.05), 13.8 for a PI-RADS 4 lesion (CI 2.3-81.3, p <0.01) and 25 for a PI-RADS 5 lesion (CI 3.8-163.5, p <0.01). When cross-tabulating these factors, men with a PI-RADS score of 3 or greater with a prostate specific antigen density of 0.16 ng/ml/cc or more had a 61.2% chance of up staging. Conversely, in men with PI-RADS score 3 or less and prostate specific antigen density less than 0.15, no up staging was seen. CONCLUSIONS: A combination of PI-RADS score and prostate specific antigen density predicts patients at risk for up staging at surveillance biopsy. Conversely, this combination may help determine which men may safely forgo biopsy.

Culturing of female bladder bacteria reveals an interconnected urogenital microbiota.

Metagenomic analyses have indicated that the female bladder harbors an indigenous microbiota. However, there are few cultured reference strains with sequenced genomes available for functional and experimental analyses. Here we isolate and genome-sequence 149 bacterial strains from catheterized urine of 77 women. This culture collection spans 78 species, representing approximately two thirds of the bacterial diversity within the sampled bladders, including Proteobacteria, Actinobacteria, and Firmicutes. Detailed genomic and functional comparison of the bladder microbiota to the gastrointestinal and vaginal microbiotas demonstrates similar vaginal and bladder microbiota, with functional capacities that are distinct from those observed in the gastrointestinal microbiota. Whole-genome phylogenetic analysis of bacterial strains isolated from the vagina and bladder in the same women identifies highly similar Escherichia coli, Streptococcus anginosus, Lactobacillus iners, and Lactobacillus crispatus, suggesting an interlinked female urogenital microbiota that is not only limited to pathogens but is also characteristic of health-associated commensals.

Molecular targets of nutraceuticals derived from dietary spices: potential role in suppression of inflammation and tumorigenesis.

Despite the fact cancer is primarily a preventable disease, recent statistics indicate cancer will become the number one killer worldwide in 2010. Since certain cancers are more prevalent in the people of some countries than others, suggests the role of lifestyle. For instance cancer incidence among people from the Indian subcontinent, where most spices are consumed, is much lower than that in the Western World. Spices have been consumed for centuries for a variety of purposes-as flavoring agents, colorants, and preservatives. However, there is increasing evidence for the importance of plant-based foods in regular diet to lowering the risk of most chronic diseases, so spices are now emerging as more than just flavor aids, but as agents that can not only prevent but may even treat disease. In this article, we discuss the role of 41 common dietary spices with over 182 spice-derived nutraceuticals for their effects against different stages of tumorigenesis. Besides suppressing inflammatory pathways, spice-derived nutraceuticals can suppress survival, proliferation, invasion, and angiogenesis of tumor cells. We discuss how spice-derived nutraceuticals mediate such diverse effects and what their molecular targets are. Overall our review suggests "adding spice to your life" may serve as a healthy and delicious way to ward off cancer and other chronic diseases.