Transurethral resection of prostatic abscess.

Prostate abscess (PA) is an uncommon prostatic infection, with risk factors including indwelling catheters, acute or chronic prostatitis, bladder outlet obstruction, voiding dysfunction, recent urologic instrumentation (especially transrectal prostate biopsy), chronic kidney disease (CKD), diabetes mellitus (DM), human immunodeficiency virus (HIV), intravenous drug use (IVDU), and hepatitis C. Treatment of PA consists of antibiotics and abscess drainage via transurethral resection (TUR) or image-guided transrectal or transperineal drainage. Numerous studies have demonstrated that TUR of PA has a higher success rate and shorter hospital length of stay when compared to image-guided drainage. Despite this, TUR of PA is a relatively uncommon surgery with few useful recommendations on how to best perform this procedure. We demonstrate the TUR surgical technique for drainage of a 6 cm loculated PA in a 44-year-old man with active IVDU and hepatitis C. The patient presented with progressive voiding symptoms, urinary retention, and leukocytosis. Given the size, loculated nature of the abscess, and its proximity to the prostatic urethra, we decided to proceed to the operating room for surgical drainage as opposed to image-guided transrectal drainage. Herein we describe the trans urethral technique. He clinically improved postoperatively and repeat imaging 4 days later showed decreased abscess size. Transurethral drainage of a PA is a safe, efficient, and effective treatment option. Treatment approach should depend on abscess size, location, and presence of loculations. Combining different endourologic techniques and instruments may be necessary.

Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials.

AIMS: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit. METHODS: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated. RESULTS: Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection. CONCLUSION: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.

Pyroptosis engagement and bladder urothelial cell-derived exosomes recruit mast cells and induce barrier dysfunction of bladder urothelium after uropathogenic E. coli infection.

The specific regulatory mechanism of bladder urothelial barrier dysfunction after infection with uropathogenic Escherichia coli (UPEC) is still unclear. The cross talk between bladder urothelial cells and mast cells may play an important role during UPEC infection. In this study, the pyroptosis of urothelial cells was investigated after UPEC infection both in vivo and in vitro. The levels of IL-1ß and IL-18 in exosomes derived from bladder urothelial cells after UPEC infection were detected. The role of these processes in the recruitment and activation of mast cells was measured. The mechanism of mast cell-induced disruption of bladder epithelial barrier function was also assessed. We found that UPEC infection induced pyroptosis of bladder urothelial cells and led to the release of IL-1ß and IL-18 in the form of exosomes, which promoted the migration of mast cells. Tryptase secreted by mast cells aggravated the damage to the barrier function of the bladder urothelium by acting on protease-activated receptor 2 (PAR2). Inhibition of pyroptosis or the tryptase-PAR2 axis reduced the disruption of bladder urothelial barrier function and decreased the bacterial burden. The present study supports a novel mechanism by which pyroptosis-dependent release of exosomes from bladder urothelial cells activates mast cells and regulates bladder urothelial barrier function during UPEC infection.

Bladder urothelial BK channel activity is a critical mediator for innate immune response in urinary tract infection pathogenesis.

The open probability of calcium-activated voltage-gated potassium channel (BK channel) on bladder umbrella urothelial cells is increased by lipopolysaccharide (LPS). It is hypothesized that this channel's activity is important in the urothelial innate immune response during urinary tract infection (UTI). We performed in vivo studies using female C57BL/6 mice whose bladders were inoculated with LPS (150 µl of 1 mg/ml) or uropathogenic Escherichia coli (UPEC, UTI89), without and with intravesical BK inhibitor iberiotoxin (IBTX, 1 µM). Inflammatory biomarkers (chemokines and cytokines) were measured in urine specimens collected 2 h after inoculation using a 32-multiplex ELISA. Of these 32 biomarkers, 19 and 15 were significantly elevated 2 h after LPS and UPEC exposure, respectively. IBTX significantly abrogated the elevations of 15 out of 19 biomarkers after LPS inoculation and 12 out of 15 biomarkers after UPEC inoculation. In a separate experiment, qPCR for IL-6, interferon-γ-induced protein 10 (CXCL10), and macrophage inflammatory protein 2 (CXCL2) in urothelium paralleled the changes measured in urine of these same biomarkers, supporting that urinary changes in biomarker levels reflected urothelial expression changes. These in vivo data demonstrated that BK channel activity is crucial in the urothelial host innate immune response, as measured by changes in urinary biomarkers, in UTI pathogenesis.

Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline.

PURPOSE: This document seeks to establish guidance for the evaluation and management of women with recurrent urinary tract infections (rUTI) to prevent inappropriate use of antibiotics, decrease the risk of antibiotic resistance, reduce adverse effects of antibiotic use, provide guidance on antibiotic and non-antibiotic strategies for prevention, and improve clinical outcomes and quality of life by reducing recurrence of urinary tract infection (UTI) events. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to January Week 1 2018), Cochrane Central Register of Controlled Trials (through December 2017) and Embase (through January 16, 2018). An update literature search was conducted on September 20, 2018. RESULTS: When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. CONCLUSIONS: Our ability to diagnose, treat, and manage rUTI long-term has evolved due to additional insights into the pathophysiology of rUTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy, rising rates of bacterial antimicrobial resistance (AMR), and better reporting of the natural history and clinical outcomes of acute cystitis and rUTI. As new data continue to emerge in this space, this document will undergo review to ensure continued accuracy.

Lipopolysaccharide stimulates BK channel activity in bladder umbrella cells.

Bladder urothelium plays an active role in response to bacterial infection. There is little known about the electrophysiological activity in urothelial cells in this process. We used a nonenzymatic method to isolate bladder urothelial tissue and to patch clamp umbrella cells in situ. A 200 pS conductance potassium (K+) channel was detected from female C57BL6 mice. Of 58 total patches, 17.2% patches displayed the 200 pS K+ conductance channel. This K+ conductance channel showed Ca2+ sensitivity and voltage dependence. Specific big-conductance potassium channel (BK) inhibitors (paxilline, iberiotoxin) blocked the 200 pS K+ conductance channel activity. RT-PCR and immunoblot confirmed BK channel pore-forming α-subunit (BK-α) mRNA and protein in urothelium. Immunohistochemistry also showed the BK-α located in urothelium. The above data provided evidence that the 200 pS K+ conductance channel was a BK channel. Lipopolysaccharide (LPS), a component of uropathogenic Escherichia coli, was used to investigate the role of BK channel in the pathogenesis of urinary tract infection. BK channel activity as NPo increased threefold within 30 min of exposure to LPS. mRNAs for LPS receptors (TLR4, CD14, MD-2) were expressed in the urothelium but not in lamina propria or detrusor. Blockade of the receptors by an antagonist (polymyxin B) abrogated LPS's effect on BK channel. The involvement of protein kinase A (PKA) on BK channel activity was demonstrated by applying PKA blockers (H89 and PKI). Both PKA inhibitors abolished the BK channel activity induced by LPS. In conclusion, BK channel was identified in bladder umbrella cells, and its activity was significantly increased by LPS.

Mouse urothelial genes associated with voiding behavior changes after ovariectomy and bladder lipopolysaccharide exposure.

AIMS: Symptoms from overactive bladder (OAB) and cystitis secondary to urinary tract infection (UTI) can be similar in post-menopausal women. Effects of ovariectomy (OVX) on voiding behavior after lipopolysaccharide (LPS) intravesical exposure (surrogate for cystitis) in mice were measured. Urothelial genes associated with micturition changes were identified. METHODS: Female C57BL6/J mice underwent OVX or sham surgeries (n = 10 for each). Voiding spot assays (VSA) were performed prior to surgery, 4 weeks post-surgery, and each time after 3 consecutive days of transurethral instillation of LPS. In another experiment, mice underwent either sham (n = 9) or OVX (n = 9) surgeries. Urothelial RNAs were collected 4 weeks post-surgery, day 1 and day 3 after LPS instillation. Mouse Gene 2.0 ST Arrays (entire 34 K transcripts) were used for microarray hybridization. A set of criteria was utilized to identify gene expression changes that mimicked voiding behavior changes. RESULTS: Three days after LPS exposure, OVX mice persisted with overactive whereas sham mice normalized voiding behavior. Nine urothelial paralleling voiding behavior changes were identified: IL6 (interleukin 6), IL6rα (Interleukin 6 receptor α), Ptgs2 (Prostaglandin-endoperoxide synthase 2 or COX-2), Ereg (epiregulin), Dusp6 (dual specificity phosphatase 6), Zfp948 (zinc finger protein 948), Zfp52 (Zinc finger protein 52), Gch1 (GTP cyclohydrolase 1), and Amd (S-adenosylmethionine decarboxylase). Three other genes, coding unknown proteins, were also identified: GM12840, GM23134, and GM26809. CONCLUSIONS: OVX mice persisted with increased voiding frequency after LPS. Urothelial genes that could mediate this voiding behavior include IL6, COX-2, and S-adenosylmethionine decarboxylase.

Future Directions of Research and Care for Urinary Incontinence: Findings from the National Institute of Diabetes and Digestive and Kidney Diseases Summit on Urinary Incontinence Clinical Research in Women.

PURPOSE: Female urinary incontinence is prevalent, costly and morbid. Participants in a NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) sponsored summit reviewed findings from NIH (National Institutes of Health) funded clinical research on urinary incontinence in women and discussed the future of urinary incontinence research. MATERIALS AND METHODS: The NIDDK convened the Summit on Urinary Incontinence Clinical Research in Women on March 14, 2014. Participants representing a broad range of clinical expertise reviewed completed NIH sponsored urinary incontinence related studies, including results from community based epidemiological studies such as the BACH (Boston Area Community Health) Survey and from randomized clinical trials such as PRIDE (Program to Reduce Incontinence by Diet and Exercise), and studies conducted by the Pelvic Floor Disorders Network and the Urinary Incontinence Treatment Network. RESULTS: BACH Survey results improved our understanding of precursors, incidence, prevalence and natural history of urinary incontinence in a diverse group of women. The Pelvic Floor Disorders Network study found that anticholinergic medications and onabotulinumtoxinA are efficacious for treating urge urinary incontinence, and Burch colposuspension and retropubic mid urethral polypropylene slings are efficacious for decreasing stress urinary incontinence following pelvic organ prolapse surgery in women with potential stress urinary incontinence. The Urinary Incontinence Treatment Network study found that fascial slings were better than colposuspension, and that retropubic and transobturator mid urethral polypropylene slings were equivalent for stress urinary incontinence. In patients with stress urinary incontinence a preoperative urodynamic study was noninferior to basic office examinations for surgical outcome. The addition of behavioral intervention did not allow female patients to discontinue antimuscarinics for urge urinary incontinence. PRIDE showed that modest weight reductions significantly decreased urinary incontinence. CONCLUSIONS: Strategies for future research on urinary incontinence should include a focus on early disease, risk factor identification, better phenotyping, incorporation of new technologies, patient centered research and prevention.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by female mouse bladder urothelial cells and expressed by the urothelium as an early response to lipopolysaccharides (LPS).

AIMS: We studied in vitro and in vivo response of primary mouse bladder urothelial cells (mBUC) and bladder urothelium to lipopolysaccharides (LPS), focusing on granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. METHODS: Female C57BL/6 mBUC were exposed for 12 hr to differing concentrations of LPS (100 ng/ml to 10 µg/ml). mBUC were also exposed to a single dose of LPS (1 µg/ml) for 3, 6, 12 hr. Neutralizing GM-CSF antibody (0.1 µg/ml) was used block GM-CSF activity in vitro. In vivo experiments were performed, whereby, LPS (1 mg/ml) was instilled intravesically and left to dwell for 30 min followed by harvest of bladder urothelium 3 to 18 hr later. ELISA measured GM-CSF. qPCR quantitated mRNA for GM-CSF, vascular endothelial growth factor-A (VEGF-A), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor α (TNF-α). RT-PCR was used to detect mRNA for GM-CSF, GM-CSFRα, and ß in bladder tissues. Immunohistofluorescence and Western blots for GM-CSFRα were performed on bladder tissues. RESULTS: LPS induced a dose-dependent release of GM-CSF by mBUC. Mouse bladder urothelium did not express GM-CSF mRNA at baseline, but expressed GM-CSF mRNA 3 hr after in vivo LPS exposure, with GM-CSF mRNA expression disappearing 18 hr later. GM-CSFRα expression was confirmed in bladder urothelium. GM-CSF neutralizing antibody significantly diminished LPS-induced increases of VEGF and COX-2 mRNA expression. CONCLUSIONS: Urothelium and mBUC secreted GM-CSF as an early response to LPS. GM-CSF mediated downstream expression of VEGF and COX-2. Urothelial GM-CSF may function as a signaling mediator for both inflammation and pain transduction. Neurourol. Urodynam. 36:1020-1025, 2017. © 2016 Wiley Periodicals, Inc.

Preoperative Urodynamic Parameters (Valsalva Leak Point Pressure and Maximum Urethral Closure Pressure), Urinary Collagen and Plasma Vitamin D Levels as Predictors of Mid Urethral Sling Surgery Outcome.

PURPOSE: To determine the best predictor of the mid urethral sling outcome we calculated the AUC of ROC curves of preoperative parameters, including Valsalva leak point pressure, maximum urethral closure pressure, urinary NTx (N-telopeptide of crosslinked type I collagen) and plasma vitamin D values (D2, D3 and D2 plus D3). MATERIALS AND METHODS: This was an ancillary study of TOMUS (Trial of Mid-urethral Slings) and the ValUE (Value of Urodynamics Evaluation) trial in which subjects underwent mid urethral sling surgery for stress urinary incontinence. Valsalva leak point pressure and maximum urethral closure pressure were measured in 427 subjects, whereas NTx, vitamin D2, vitamin D3 and vitamin D2 plus D3 levels were obtained from 150, 116, 115 and 116 subjects respectively. Outcome success was defined using identical outcome (subjective and objective) variables for all subjects. ROC curves with corresponding AUC values were compared. RESULTS: TOMUS and ValUE subjects were significantly different in age, body mass index, UDI (Urogenital Distress Inventory) scores. TOMUS subjects had a lower surgical success rate compared to ValUE subjects (66.3% vs 76.0%, p = 0.03). The AUC values of Valsalva leak point pressure, maximum urethral closure pressure, NTx, and vitamins D2, D3 and D2 plus D3 were 0.542, 0.561, 0.702, 0.627, 0.645 and 0.640, respectively. The AUC of NTx was significantly higher than the AUCs of Valsalva leak point pressure and maximum urethral closure pressure (p = 0.02 and 0.03, respectively). CONCLUSIONS: Urinary NTx was the best predictor of the mid urethral sling outcome. This test is not only noninvasive, it is also modifiable. Finding ideal modifiable risk factors prior to mid urethral sling surgery should be subject to future investigations.

The cost of preoperative urodynamics: A secondary analysis of the ValUE trial.

AIMS: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. METHODS: This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS). All participants underwent an OE; those patients who randomized to supplementary UDS underwent non-instrumented uroflowmetry, filling cystometry, and a pressure flow study. Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees. Models using various patient populations and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States. RESULTS: Six hundred thirty women were randomized to OE or OE plus UDS. There was no difference in surgical outcomes between the two groups. The per patient cost of UDS varied from site to site, and included complex cystometrogram $314-$343 (CPT codes 51728-51729) plus complex uroflowmetry $16 (CPT code 51741). Extrapolating these costs for US women similar to our study population, 13-33 million US dollars could be saved annually by not performing preoperative urodynamics. CONCLUSION: For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation, tens of millions of dollars US could be saved annually by not performing urodynamic testing. In the management of such women, eliminating this preoperative test has a major economic benefit.

A randomized trial of urodynamic testing before stress-incontinence surgery.

BACKGROUND: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes. METHODS: We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points. RESULTS: A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes. CONCLUSIONS: For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).

The future of research in female pelvic medicine.

Female pelvic medicine and reconstructive surgery (FPMRS) was recently recognized as a subspecialty by the American Board of Medical Specialties (ABMS). FPMRS treats female pelvic disorders (FPD) including pelvic organ prolapse (POP), urinary incontinence (UI), fecal incontinence (FI), lower urinary tract symptoms (LUTS), lower urinary tract infections (UTI), pelvic pain, and female sexual dysfunction (FSD). These conditions affect large numbers of individuals, resulting in significant patient, societal, medical, and financial burdens. Given that treatments utilize both medical and surgical approaches, areas of research in FPD necessarily cover a gamut of topics, ranging from mechanistically driven basic science research to randomized controlled trials. While basic science research is slow to impact clinical care, transformational changes in a field occur through basic investigations. On the other hand, clinical research yields incremental changes to clinical care. Basic research intends to change understanding whereas clinical research intends to change practice. However, the best approach is to incorporate both basic and clinical research into a translational program which makes new discoveries and effects positive changes to clinical practice. This review examines current research in FPD, with focus on translational potential, and ponders the future of FPD research. With a goal of improving the care and outcomes in patients with FPD, a strategic collaboration of stakeholders (patients, advocacy groups, physicians, researchers, professional medical associations, legislators, governmental biomedical research agencies, pharmaceutical companies, and medical device companies) is an absolute requirement in order to generate funding needed for FPD translational research.

Inflammatory and tissue remodeling urinary biomarkers before and after mid urethral sling surgery for stress urinary incontinence.

PURPOSE: Urinary biomarkers were measured in women at baseline and 1 year after surgery for stress urinary incontinence, and associations with clinicodemographic covariates and outcomes were analyzed. MATERIALS AND METHODS: Preoperative and postoperative urine specimens from 150 women were assayed for inflammatory biomarkers (tumor necrosis factor-α, interferon-γ, interleukin-1ß, interleukin-6, interleukin-10, interleukin-12p70, interleukin-17 and nerve growth factor) and tissue remodeling biomarkers (collagenase activity, matrix metalloproteinases-1, 2, 9 and 13, and NTx [N-telopeptide cross-linked collagen], epidermal growth factor and heparin-binding epidermal growth factor-like growth factor). Paired t-tests were used to compare changes in biomarkers during 1 year (significance p <0.05). Linear regression models correlated baseline and changes in biomarker levels with covariates (significance p ≤ 0.001). Logistic regression models, controlling for age, were used to analyze associations of baseline and changes in biomarker levels with surgical failure (significance p <0.05). RESULTS: During 1 year interleukin-12p70 decreased (mean ± SD 0.53 ± 1.4 to 0.28 ± 0.62 pg/mg creatinine, p = 0.04) and nerve growth factor increased (0.034 ± 0.046 to 0.044 ± 0.060 pg/ml/mOsm, p = 0.03). Baseline NTx level per mg creatinine was positively associated with age and postmenopausal status (p = 0.001), and negatively associated with current estrogen use (p = 0.0001). Baseline collagenase activity per mg creatinine was positively associated with age (p = 0.001). Epidermal growth factor per mOsm, NTx per mOsm and interferon-γ per mOsm were negatively correlated with age, current estrogen use and UDI (Urogenital Distress Inventory)-irritative subscale score, respectively (p ≤ 0.001). Subjects with lower baseline NTx per mg creatinine were less likely to experience surgical failure (OR 0.49, 95% CI 0.26-0.93, p = 0.03). Changes in biomarker levels were not associated with any covariates or surgical failure. CONCLUSIONS: Stress urinary incontinence surgery was significantly less likely to fail in women with lower baseline NTx levels. Studies are needed to validate NTx as a possible independent biomarker for stress urinary incontinence surgery outcomes.

Urinary incontinence management costs are reduced following Burch or sling surgery for stress incontinence.

OBJECTIVE: The objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence (UI) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a randomized trial comparing these procedures. STUDY DESIGN: Resources used for UI management (supplies, laundry, dry cleaning) were self-reported by 491 women at baseline and 24 months after surgery, and total out-of-pocket costs for UI management (in 2012 US dollars) were estimated. Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months. Univariate and bivariate changes in cost were analyzed using the Wilcoxon signed rank test. Predictors of change in cost were examined using multivariate mixed models. RESULTS: At baseline mean (±SD) age of participants was 53 ± 10 years, and the frequency of weekly UI episodes was 23 ± 21. Weekly UI episodes decreased by 86% at 24 months (P < .001). The mean weekly cost was $16.60 ± $27.00 (median $9.39) at baseline and $4.57 ± $15.00 (median $0.10) at 24 months (P < .001), a decrease of 72%. In multivariate analyses, cost decreased by $3.38 ± $0.77 per week for each decrease of 1 UI episode per day (P < .001) and was strongly associated with greater improvement in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores (P < .001) and decreased 24-hour pad weight (P < .02). CONCLUSION: Following Burch or fascial sling surgery, the UI management cost at 24 months decreased by 72% ($625 per woman per year) and was strongly associated with decreasing UI frequency. Reduced out-of-pocket expenses may be a benefit of these established urinary incontinence procedures.

The Urinary Microbiome: Improving Diagnostics and Management of Urinary Tract Infections in Adult Females.

This article discusses the urinary microbiome in relation to urinary tract infection (UTI) in women. It makes biologic sense that the microbiota of different niches (bladder, vagina, and gut) interact with each other in health, as well as during a UTI event; however, these relationships remain poorly understood. Future research should close knowledge gaps regarding the interactions between the urinary microbiota and the host, amongst the microbiota of adjacent niches, and between the microbes within the same microbiota. The new knowledge should result in improved UTI treatment in the age of antibiotic stewardship.

Elevated polyamines in urothelial cells from OAB subjects mediate oxotremorine-evoked rapid intracellular calcium rise and delayed acetylcholine release.

Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca(2+)]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca(2+)]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca(2+)]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca(2+)]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 µM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca(2+)]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC.

Retropubic versus transobturator midurethral slings for stress incontinence.

BACKGROUND: Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. METHODS: We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points. RESULTS: A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P=0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P=0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life. CONCLUSIONS: The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.)