Impact of Antibiotic Choice at the Time of Sacral Neuromodulation Implantation on Rates of Surgical Site Infection.

PURPOSE: To evaluate the efficacy of specific antibiotic regimens in preventing infection following sacral neuromodulation. MATERIALS AND METHODS: This is a retrospective cohort study utilizing the Premier Healthcare Database. Patients who underwent sacral neuromodulation placement between January 2016 and March 2020. The patients were grouped by those who received dual antibiotic therapy per 2019 AUA guidelines (Gram positive + broad Gram negative coverage), first- or second-generation cephalosporins or any other regimen. Comparison between groups was performed using Kruskal-Wallis and χ2 tests for continuous and categorical variables, respectively. Inverse probability of treatment weighted (IPTW) analysis was used to estimate the average treatment effect of AUA guidelines regimens versus the use the first- or second-generation cephalosporins alone. RESULTS: The sample included 14 179 patients, with 2211 patients receiving prophylaxis that followed the AUA guideline recommendations. There was no significant difference in surgical site infection rates within 3 months (p = 0.28) or within 12 months (p = 0.53) between the groups. On IPTW, the probability of an infection at 3 months was lower with the AUA guideline regimens compared to those who received first- or second-generation cephalosporins alone, but this difference was not statistically significant (OR = 0.73, 95% CI: [0.43, 1.24]). CONCLUSIONS: In the absence of allergies to cephalosporins or penicillin, first- or second-generation cephalosporins alone may be a sufficient preoperative antibiotic regimen for prevention of infection at the time of sacral neuromodulation. TRIAL REGISTRATION: Not applicable due to being a database study.

Perioperative antibiotic choice and postoperative infectious complications in pelvic organ prolapse surgery.

OBJECTIVE: The objective of this study was to determine how rates of postoperative infectious complications after pelvic organ prolapse surgery differ based on perioperative antibiotic administered. In particular, we sought to determine whether anaerobic coverage is associated with reduced rates of infectious complications. DESIGN: This was a retrospective cohort study. SETTING: Premier Healthcare U.S. national database, a comprehensive all-payer dataset capturing patients from urban and rural non-profit, community, and teaching hospitals. PARTICIPANTS: Adult patients who underwent vaginal, laparoscopic, and/or abdominal prolapse surgery with or without hysterectomy from January 2000 to March 2020. Procedures with and without mesh were included. INTERVENTIONS: Rates of infectious complications were compared among patients who received guideline-concordant antibiotic regimens, including those with anaerobic coverage. The primary outcome was any surgical site infection within 30 days of surgery without mesh or 90 days of surgery involving mesh. RESULTS: Among 130,198 prolapse surgeries, the most common antibiotic regimens were cefazolin (n=97,058, 74.5%), second generation cephalosporin (n=16,442, 12.6%), clindamycin + aminoglycoside (n=8,397, 6.4%) and cefazolin + metronidazole (n=4,328, 3.3%). On multivariable logistic regression, only clindamycin + aminoglycoside was associated with a higher rate of surgical site infections (OR 1.37; 95% CI 1.09-1.72) and other infectious morbidity (OR 1.26; 95% CI 1.12-1.42) when compared to cefazolin alone. The addition of metronidazole to cefazolin was not associated with reduced rates of surgical site infections (OR 1.09; 95% CI 0.82 - 1.45). Obesity (OR=1.22; 95% CI 1.03-1.43), diabetes without complication (OR=1.30; 95% CI 1.08-1.57), Charlson comorbidity score >0 (OR=1.24; 95% CI 1.06-1.45), and tobacco use (OR=1.22, 95% CI 1.05-1.40) were also associated with increased composite surgical site infection. CONCLUSION: Compared with cefazolin alone, the use of alternative perioperative antibiotics, including those with anaerobic coverage, was not associated with reduced infectious complications after pelvic organ prolapse surgery in this U.S. national sample.

Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2interleukin (IL)-4,IL-13, M2IC, M2IL-10, M2non-selective adenosine receptor agonists (NECA) (M2IL-4,IL-13 → M2NECA). In this study, rat bone marrow-derived macrophages (M0) were polarized to each of the four subtypes M2IL-4,IL-13 → M2NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases-1 (TIMP-1) for M2IL-4,IL-13, higher amounts of transforming growth factor-beta 1 (TGF-ß1) for M2IL-10, and elevated vascular endothelial growth factor A (VEGF-A) from M2NECA. Co-culture experiments performed with M2IL-10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co-cultured with M2NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of "M2" may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M2 subtype could result in more consistent long-term outcomes where macrophages are utilized as part of an overall regenerative strategy.

Risk of dementia associated with the use of anticholinergic medications: a review of recent literature.

PURPOSE OF REVIEW: While there is an established association between the use of anticholinergic medications and its effects on cognition, the extent of this impact remains unclear. We outline recent studies addressing this topic. RECENT FINDINGS: We describe a series of recent articles discussing the risk of dementia associated with anticholinergic medication use in general, with further focus on the risk of overactive bladder (OAB) anticholinergic use, detailing short & long-term use effects, risk variation based on age and gender, and reporting alternative treatment options. SUMMARY: Anticholinergic medication use bears an increased risk of dementia development, and accelerated cognitive decline in individuals with preexisting dementia, with the risk being related to the medications dosages, length of exposure, and pharmacological profile. ß3-adrenoceptor agonists have proven to be a potent alternative for OAB anticholinergics, owing to its safe profile in regards of no clear effects on cognitive function, and having similar efficacy in OAB treatment.

Prediction of Postoperative Urinary Tract Infection Following Benign Gynecologic Surgery.

INTRODUCTION AND HYPOTHESIS: The objective was to develop a prediction model for urinary tract infection (UTI) after pelvic surgery. METHODS: We utilized data from three tertiary care centers of women undergoing pelvic surgery. The primary outcome was a UTI within 8 weeks of surgery. Additional variables collected included procedural data, severity of prolapse, use of mesh, anti-incontinence surgery, EBL, diabetes, steroid use, estrogen use, postoperative catheter use, PVR, history of recurrent UTI, operative time, comorbidities, and postoperative morbidity including venous thromboembolism, surgical site infection. Two datasets were used for internal validation, whereas a third dataset was used for external validation. Algorithms that tested included the following: multivariable logistic regression, decision trees (DTs), naive Bayes (NB), random forest (RF), gradient boosting (GB), and multilayer perceptron (MP). RESULTS: For the training dataset, containing both University of British Columbia and Mayo Clinic Rochester data, there were 1,657 patients, with 172 (10.4%) UTIs; whereas for the University of Calgary external validation data, there were a total of 392 patients with a UTI rate of 16.1% (n = 63). All models performed well; however, the GB, DT, and RF models all had an area under the curve (AUC) > 0.97. With external validation the model retained high discriminatory ability, DT: AUC = 0.88, RF: AUC = 0.88, and GB: AUC = 0.90. CONCLUSIONS: A model with high discriminatory ability can predict UTI within 8 weeks of pelvic surgery. Future studies should focus on prospective validation and application of randomized trial models to test the utility of this model in the prevention of postoperative UTI.

Effect of Dietary Choline Consumption on the Development of Urinary Urgency Incontinence in a Longitudinal Cohort of Women.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to determine whether differences in the cumulative dietary intake of choline, is associated with the risk of developing urge urinary incontinence (UUI). METHODS: This was an analysis within the Nurses' Health Study (NHS) I and II. The main exposure was the cumulative daily intake for each choline-containing compound obtained from a detailed daily food frequency questionnaire. The primary outcome was UUI, defined as urine loss with a sudden feeling of bladder fullness or when a toilet is inaccessible, occurring >1/month. Cox proportional hazards regression models were used to calculate multivariate-adjusted relative risks and 95% confidence intervals (CIs) for the association between total choline and choline derivatives and risk of UUI. Fixed effects meta-analyses of results from NHSI and NHSII were performed for postmenopausal women only to obtain a pooled estimate of the impact of choline consumption on UUI. RESULTS: There were 33,273 participants in NHSI and 38,732 in NHSII who met all the criteria for inclusion in the analysis. The incidence of UUI was 9.41% (n=3,139) in NHSI and 4.25% (n=1,646) in NHSII. After adjusting for confounders choline was not found to be associated with UUI in postmenopausal women. However, in premenopausal women, relative to the lowest quartile, the highest quartile of consumption of total choline (aRR = 0.79, 95% CI: 0.64-0.99), free choline (aRR = 0.74, 95% CI: 0.58-0.94), and phosphocholine (aRR = 0.77, 95% CI: 0.61-0.96) were associated with a reduced risk of UUI. CONCLUSIONS: Increased dietary choline consumption was associated with a reduced risk of UUI among premenopausal women.

The Response of the Urinary Microbiome to Botox.

INTRODUCTION AND HYPOTHESIS: Our objective was to evaluate if botox alters the urinary microbiome of patients with overactive bladder and whether this alteration is predictive of treatment response. METHODS: This multicenter prospective cohort study included 18-89-year-old patients undergoing treatment for overactive bladder with 100 units of botox. Urine samples were collected by straight catheterization on the day of the procedure (S1) and again 4 weeks later (S2). Participants completed the Patient Global Impression of Improvement form at their second visit for dichotomization into responders and nonresponders. The microbiome was sequenced using 16s rRNA sequencing. Wilcoxon signed rank and Wilcoxon rank sum were used to compare the microbiome, whereas chi-square, Wilcoxon rank sum, and the independent t-test were utilized for clinical data. RESULTS: Sixty-eight participants were included in the analysis. The mean relative abundance and prevalence of Beauveria bassiana, Xerocomus chrysenteron, Crinipellis zonata, and Micrococcus luteus were all found to increase between S1 and S2 in responders; whereas in nonresponders the mean relative abundance and prevalence of Pseudomonas fragi were found to decrease. The MRA and prevalence of Weissella cibaria, Acinetobacter johnsonii, and Acinetobacter schindleri were found to be greater in responders than nonresponders at the time of S1. Significant UM differences in the S1 of patients who did (n = 5) and did not go on to develop a post-treatment UTI were noted. CONCLUSIONS: Longitudinal urobiome differences may exist between patients who do and do not respond to botox.

Methodological rigour in preclinical urology: a systematic review reporting research quality over a 14-year period.

OBJECTIVE: To investigate the prevalence and trends of essential study design elements in preclinical urological studies, as well as key factors that may improve methodological rigour, as the demand for methodological rigour in preclinical studies is increasing since research reproducibility and transparency in the medico-scientific field are being questioned. METHODS AND RESULTS: PubMed was searched to include preclinical urological studies published between July 2007 to June 2021. A total of 3768 articles met the inclusion criteria. Data on study design elements and animal models used were collected. Citation density was also examined as a surrogate marker of study influence. We performed an analysis of the prevalence of seven critical study design elements and temporal patterns over 14 years. Randomisation was reported in 50.0%, blinding in 15.0%, sample size estimation in 1.0%, inclusion of both sexes in 6.3%, statistical analysis in 97.1%, housing and husbandry in 47.7%, and inclusion/exclusion criteria in 5.0%. Temporal analysis showed that the implementation of these study design elements has increased, except for inclusion of both sexes and inclusion/exclusion criteria. Reporting study design elements were associated with increased citation density in randomisation and statistical analysis. CONCLUSIONS: The risk of bias is prevalent in 14-year publications describing preclinical urological research, and the quality of methodological rigour is barely related to the citation density of the article. Yet five study design elements (randomisation, blinding, sample size estimation, statistical analysis, and housing and husbandry) proposed by both the National Institutes of Health and Animal Research: Reporting of In Vivo Experiments guidelines have been either well reported or are being well reported over time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022233125.

Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis.

INTRODUCTION AND HYPOTHESIS: The development of recurrent urinary tract infections (rUTIs) is not completely understood. This review is aimed at investigating the connection between genetics and rUTIs and summarizing the results of studies that have documented variations in gene expression among individuals with rUTIs compared with healthy individuals. METHODS: A systematic search was conducted in Cochrane, Ovid, and PubMed, limiting the results to articles published between 1 January 2000, and 5 July 2022. Only studies comparing the difference in gene expression between individuals with rUTI and healthy individuals utilizing molecular techniques to measure gene expression in blood or urine samples were included in this systematic review. Gene network and pathways analyses were performed using Cytoscape software, with input data obtained from our systematic review of differentially expressed genes in rUTIs. RESULTS: Six studies met our criteria for inclusion. The selected studies used molecular biology methods to quantify gene expression data from blood specimens. The analysis revealed that gene expressions of CXCR1 and TLR4 decreased, whereas CXCR2, TRIF, and SIGIRR increased in patients with rUTI compared with healthy controls. The analysis demonstrated that the most significant pathways were associated with TLR receptor signaling and tolerance, I-kappa B kinase/NF-kappa B signaling, and MyD88-independent TLR signaling. CONCLUSIONS: This systematic review uncovered gene expression variations in several candidate genes and identified a number of underlying biological pathways associated with rUTIs. These findings could shift the treatment and prevention strategies for rUTIs.

Use of a Digital Conversational Agent for the Management of Overactive Bladder.

IMPORTANCE: Conservative therapy is effective for the treatment of overactive bladder (OAB) but may be limited by accessibility to care. OBJECTIVE: The objective of this study was to evaluate the efficacy of a digital conversational agent (CeCe) for the treatment of OAB. STUDY DESIGN: This was a prospective observational trial utilizing a digital conversational agent developed by Renalis University Hospitals (Cleveland, Ohio) for the treatment of OAB. Patients were given access to CeCe over an 8-week period and were instructed on how to perform bladder training and pelvic floor exercises and taught about bladder health. The primary outcome was a decrease in the International Consultation on Incontinence-Overactive Bladder Quality-of-Life Questionnaire (ICIQ-OAB-QoL) score from week 1 to week 8. Patients also completed the 36-item Short-Form Health Survey and Generalized Anxiety Disorder Questionnaire at the same intervals and voiding diaries at weeks 1, 4, and 8. A power analysis was performed and determined that a total of 30 patients would be needed to demonstrate a significant difference in symptom scores after use of CeCe with 80% power and an α error of 5%. RESULTS: Twenty-nine patients completed all data collection. The ICIQ-OAB-QoL scores were significantly different between weeks 1 and 8 (62 [IQR], 49-75) vs 32 [IQR, 24-43]; P < 0.001). Patients also reported a decrease in frequency pretreatment and posttreatment (7 [IQR, 6-10] vs 5 [IQR, 4-7]; P = -0.04), nocturia (2 [IQR, 1-3] vs 1 [IQR, 1-2]; P = 0.03), and urge urinary incontinence (2 [IQR, 1-5] vs 0 [IQR, 0-3]; P = 0.04). Consumption of alcohol decreased from week 1 to week 8 (24 oz [IQR, 12-36 oz) to 14 oz (IQR, 9-22 oz]; P = 0.02). CONCLUSION: The use of a digital conversational agent effectively reduced the severity of symptoms and improved quality of life in patients with OAB.

Comparison of Morbidity and Retreatment After Urethral Bulking or Midurethral Sling at the Time of Pelvic Organ Prolapse Repair.

OBJECTIVE: To compare postprocedure retreatment rates for stress incontinence in patients who underwent either midurethral sling or urethral bulking at the time of concomitant repair of pelvic organ prolapse (POP). METHODS: This was a retrospective cohort study using data from the Premier Healthcare Database. Using Current Procedural Terminology codes, we identified patients who were undergoing POP repair and concomitant urethral bulking or midurethral sling between the years 2001 and 2018. Patients who underwent concomitant nongynecologic surgery, Burch urethropexy, or oncologic surgery, and those who did not undergo concomitant POP and anti-incontinence surgery, were excluded. Additional data collected included patient demographics, hospital characteristics, surgeon volume, and comorbidities. The primary outcome was a repeat anti-incontinence procedure at 2 years, and the secondary outcome was the composite complication rate. RESULTS: Over the study period, 540 (0.59%) patients underwent urethral bulking, and 91,005 (99.41%) patients underwent midurethral sling. The rate of a second procedure within 2 years was higher for urethral bulking, compared with midurethral sling (9.07% vs 1.11%, P <.001); in the urethral bulking group, 4.81% underwent repeat urethral bulking and 4.81% underwent midurethral sling. In the midurethral sling group, 0.77% underwent repeat midurethral sling and 0.36% underwent urethral bulking. After adjusting for confounders, midurethral sling was associated with a decreased odds of a repeat anti-incontinence procedure at 2 years (adjusted odds ratio 0.11, 95% CI 0.08-0.16). The probability of any complication at 2 years was higher with urethral bulking (23.0% vs 15.0%, P <.001). CONCLUSION: Urethral bulking at the time of POP repair is associated with a higher rate of repeat procedure and postoperative morbidity up to 2 years after surgery.

Focal adhesion kinase activation is involved in contractile stimulation-induced detrusor muscle contraction in mice.

Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 µM), latrunculin B (1 µM), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2-32 Hz), or carbachol (CCh, 10-7.5-10-4.5 M) were measured. In a separate experiment, the phosphorylated FAK (p-FAK) and MLC (p-MLC) levels were measured in the detrusor strips stimulated with CCh (10 µM) after incubation with PF-573228 or vehicle (DMSO) compared to those with vehicle incubation but without CCh stimulation. KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle-treated strips (p < 0.0001). The contractile responses induced by EFS were markedly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (p < 0.05) or latrunculin B at 16 and 32 Hz (p < 0.01). Following the application of PF-573228 or Latrunculin B, CCh-induced dose-response contractions were lower than the corresponding vehicle group (p = 0.0021 and 0.0003, respectively). Western blot examination showed that CCh stimulation enhanced the expression of p-FAK and p-MLC, while preincubation with PF-573228 prevented the increase of p-FAK but not p-MLC. In conclusion, FAK activation involves tension development induced by contractile stimulation in the mouse detrusor muscle. This effect is likely caused by promoting actin polymerization rather than elevating MLC phosphorylation.

Development of a machine learning-based predictive model for prediction of success or failure of medical management for benign prostatic hyperplasia.

OBJECTIVE: To develop a novel predictive model for identifying patients who will and will not respond to the medical management of benign prostatic hyperplasia (BPH). METHODS: Using data from the Medical Therapy of Prostatic Symptoms (MTOPS) study, several models were constructed using an initial data set of 2172 patients with BPH who were treated with doxazosin (Group 1), finasteride (Group 2), and combination therapy (Group 3). K-fold stratified cross-validation was performed on each group, Within each group, feature selection and dimensionality reduction using nonnegative matrix factorization (NMF) were performed based on the training data, before several machine learning algorithms were tested; the most accurate models, boosted support vector machines (SVMs), being selected for further refinement. The area under the receiver operating curve (AUC) was calculated and used to determine the optimal operating points. Patients were classified as treatment failures or responders, based on whether they fell below or above the AUC threshold for each group and for the whole data set. RESULTS: For the entire cohort, the AUC for the boosted SVM model was 0.698. For patients in Group 1, the AUC was 0.729, for Group 2, the AUC was 0.719, and for Group 3, the AUC was 0.698. CONCLUSION: Using MTOPS data, we were able to develop a prediction model with an acceptable rate of discrimination of medical management success for BPH.

Correlates of health-seeking behavior for sexual dysfunction after childbirth: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: Persistent sexual dysfunction (SD) after childbirth is common, but many patients do not receive adequate care, for unknown reasons. The aim of this study is to examine correlates for health care-seeking behavior for SD within 3 years after birth. METHODS: Subjects filled out an electronic survey regarding sexual function, obstetric, relationship, and demographic characteristics. The Sexual Function Questionnaire's Medical Impact Scale) as well as a number of novel, targeted survey questions were used to measure the impact of childbirth on sexual function. Patients were stratified into those without SD, and those with SD, both seeking and not seeking care. These domains were then compared in a series of univariate, bivariate, and multivariate analyses. RESULTS: Of 531 patients who completed the survey, 449 women (84.5%) reported some form of SD after birth. Only 16.0% of those with SD sought care for SD. Variables associated with care seeking include difficulty with perineal healing (adjusted odds ratio [aOR]=4.53, 95% confidence interval [CI]: 1.54-13.38), transfusion after birth (aOR=3.71, 95% CI: 1.44-9.56), current dyspareunia (aOR=3.41, 95% CI: 1.31-8.87). Factors associated with decreased probability of seeking care include children under 18 years in the home (aOR=0.61 per child, 95% CI: 0.43-0.88), number of cesarean births (aOR=0.46 per delivery, 95% CI: 0.29-0.74). CONCLUSIONS: This study highlights that many more women suffer from SD after childbirth than seek care, and identified several important risk factors associated with decreased care seeking. Future work should focus on decreasing the difficulty of accessing care for SD after childbirth.

Opioid use following pelvic reconstructive surgery: a predictive calculator.

INTRODUCTION AND HYPOTHESIS: Our objective was to evaluate the amount of opioids used by patients undergoing surgery for pelvic floor disorders and identify risk factors for opioid consumption greater than the median. METHODS: This was a prospective cohort study of 18- to 89-year-old women undergoing major urogynecological surgery between 1 November2020 and 15 October 2021. Subjects completed one preoperative questionnaire ("questionnaire 1") that surveyed factors expected to influence postoperative pain and opioid use. At approximately 1 and 2 weeks following surgery, patients completed two additional questionnaires ("questionnaire 2" and "questionnaire 3") about their pain scores and opioid use. Risk factors for opioid use greater than the median were assessed. Finally, a calculator was created to predict the amount of opioid used at 1 week following surgery. RESULTS: One hundred and ninety patients were included. The median amount of milligram morphine equivalents prescribed was 100 (IQR 100-120), whereas the median amount used by questionnaire 2 was 15 (IQR 0-50) and by questionnaire 3 was 20 (IQR 0-75). On multivariate logistic regression, longer operative time (aOR 1.64 per hour of operative time, 95% CI 1.07-2.58) was associated with using greater than the median opioid consumption at the time of questionnaire 2; whereas for questionnaire 3, a diagnosis of fibromyalgia (aOR=16.9, 95% CI 2.24-362.9) was associated. A preliminary calculator was created using the information collected through questionnaires and chart review. CONCLUSIONS: Patients undergoing surgery for pelvic floor disorders use far fewer opioids than they are prescribed.

The impact of urinary incontinence on multiple health outcomes: an umbrella review of meta-analysis of observational studies.

BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.

A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.

OBJECTIVE: The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes. DATA SOURCES: We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone. METHODS: A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder. RESULTS: A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes. CONCLUSION: Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.

Comparison of Morphological and Histological Characteristics of Human and Sheep: Sheep as a Potential Model for Testing Midurethral Slings in vivo.

INTRODUCTION: The sheep was evaluated as a potential model for preclinical evaluation of urethral slings in vivo based on: (1) anatomical measurements of the sheep vagina and (2) histological tissue integration and host response to polypropylene (PP) slings. METHODS: Eight female, multiparous sheep were utilized. Three of 8 animals underwent surgery mimicking human tension-free vaginal tape protocols for midurethral slings and were euthanized at 6 months. The following measurements were obtained: vaginal length, maximum vaginal width with retraction, symphysis pubis length, and distance from the pubic bone to incision. Explanted sling samples from sheep and human were stained with hematoxylin and eosin for host reaction assessment. RESULTS: Geometric measurements were similar between humans and sheep. Sheep vaginal anatomy allowed sling placement similar to procedures in human surgeries, and all sheep recovered without problems. Comparative histology between the sheep and human indicated similar host reaction and collagen deposition around implants, confirming suitability of the sheep model for biomaterial response assessment. CONCLUSION: Sheep vaginal length is comparable to humans. Tissue integration and host response to PP slings showed chronic inflammation with rich collagen deposition around the material in both sheep and human specimens, highlighting the sheep as a potential animal model for preclinical testing of midurethral slings.

Effects of different diets used to induce obesity/metabolic syndrome on bladder function in rats.

Preclinical and human studies on the relationship between obesity/metabolic syndrome (MetS) and lower urinary tract dysfunction (LUTD) are inconsistent. We compared the temporal effects of feeding four different diets used to induce obesity/MetS, including 60% fructose, 2% cholesterol +10% lard, 30% fructose + 20% lard, or 32.5% lard diet, up to 42 wk, on metabolic parameters and bladder function in male Sprague-Dawley rats. Rats fed a 30% fructose + 20% lard or 32.5% lard diet consumed less food (grams), but only the 32.5% lard diet group took in more calories. Feeding rats a 60% fructose or 30% fructose + 20% lard diet led to glucose intolerance and increased blood pressure. Higher body weight and increased cholesterol levels were observed in the rats maintained on a 2% cholesterol +10% lard diet, whereas exposure to a 32.5% lard diet affected most of the above parameters. Voiding behavior measurement showed that voiding frequency and the total voided volume were lower in the experimental diet groups except for the 30% fructose + 20% lard group. The mean voided volume was lower in the 30% fructose + 20% lard and 32.5% lard groups compared with the control group. Cystometric analysis revealed a decreased bladder capacity, mean voided volume, intermicturition interval, and compliance in the 32.5% lard diet group. In conclusion, experimental diets including 60% fructose, 30% fructose + 20% lard, or 2% cholesterol + 10% lard diet differently affected physiological and metabolic parameters and bladder function to a limited extent, while exposure to a 32.5% lard diet had a greater impact.

A study on etiology of incontinence in double knockout mouse model.

INTRODUCTION AND OBJECTIVE: Stress urinary incontinence is of concern in both pediatric and adult population. Double mutant GLI family zinc finger Gli2+/-; Gli3Δ699/+ murine model of stress incontinence has been recently developed as a reliable model which does not require surgical manipulation to create incontinence and is shown to survive to adulthood. The aim of this study was to establish the etiology of incontinence in the double mutant Gli2+/-; Gli3Δ699/+ mice. STUDY DESIGN: We used 13 cluster of differentiation 1 (CD-1) mice (7-9 weeks) for demonstration of histology of the bladder and urethra. There were 3 Wild Gli2+/- females, 2 Wild Gli2+/- males, 4 Gli2+/-;Gli3Δ699/+ females and 4 Gli2+/-;Gli3Δ699/+ males. The Wild Gli2+/- mice served as the control group and Gli2+/-;Gli3Δ699/+ mice served as the test group. Additionally, eight 16.5 days mice (2 each of Wild Gli2+/- females, Wild Gli2+/- males, double knockout (DKO) Gli2+/-;Gli3Δ699/+ females and Gli2+/-;Gli3Δ699/+ males) were used to assess the histology of the spinal cord. The gross appearance of bladder and urethra was studied using ink injection assays. Immunohistochemistry was done for smooth muscle actin and cytokeratin. RESULTS: Gross and histologic appearance confirmed the previously reported widening of bladder outlet and hypoplasia of smooth muscles in female urethra and also established them in the male urethra of Gli2+/-;Gli3Δ699/+ mice compared to Gli2+/- mice. The double knockout mice were smaller than the Gli2 mice (5.2 vs 6.1 cm, p = 0.002). Immunohistochemistry demonstrated epithelial hyperplasia and smooth muscle hypoplasia. Additionally, there was prostatic hypoplasia in the Gli2+/-;Gli3Δ699/+ male mice. The spinal cord length for body size appeared comparable between the Gli2+/- and Gli2+/-;Gli3Δ699/+ mice but histological evaluation revealed abnormal development of the caudal end of the vertebral body with premature termination of the spinal cord (Figure). DISCUSSION: The histological changes in the bladder neck and urethra were consistent to those previously reported. While previous report described the findings in female mice only, we confirmed that these findings are also present in males as well as prostatic hypoplasia, a possible additional factor leading to stress incontinence. The most important finding in the present study however, was the detection of premature termination of spinal cord in the DKO Gli2+/-; Gli3Δ699/+ mice which has not been reported previously and is likely a major contributor to incontinence in this model. CONCLUSION: The incontinence in male as well as female Gli2+/-; Gli3Δ699/+ mice is due to both myogenic and neurogenic involvement. These double knockout mice are a valuable model of stress incontinence related to neurogenic bladder due to low outlet resistance.