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.

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.

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.

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.

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.

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 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.

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.

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.

Evaluation of the relationship of cholinergic metabolites in urine and urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To investigate differences in urine cholinergic metabolites in women with urinary urgency incontinence (UUI) and responders (R) and non-responders (NR) to anti-cholinergic medications (AC). METHODS: Patients with UUI and age-matched controls were evaluated pre- and post-treatment using OABSS, UDI-6 and IIQ-7. Controls were defined as having a cumulative OABSS of zero. Patients with UUI were treated with AC and followed for 12 weeks. Responders were those with a > 50% decrease in the total OABSS score. Urine samples were collected from all participants for evaluation. Metabolite detection was accomplished using commercial assay kits. Wilcoxon-rank sum test and Fisher's exact test were used to express differences between groups. Spearman's rho correlation coefficient was used to determine the relationship between acetylcholine (Ach), choline (Ch), acetylcholinesterase (AchE) and questionnaire scores. RESULTS: We recruited 39 with UUI and 33 controls. We found concentrations of Ch [29.0 (IQR: 24.2-42.5) µmol vs. 15.2 (IQR: 7.5-24.1) µmol] and Ach [65.8 (IQR: 30.4-101.8) nmol and 33.1 (IQR: 11.9-43.8) nmol] were higher in the UUI group compared to controls (p = 0.003 and p < 0.001, respectively] and no differences in AchE concentrations. In the UUI group, 43.6% responded to AC after 12 weeks of therapy. There were no differences in Ch or AchE levels between R and NR; Ach levels were higher in the R group [82.1 nmol (IQR: 54.8-118.1) vs. 50.3 nmol (IQR: 29.9-68.2), p = 0.007]. Ch and Ach were positively associated with pre-treatment OABSS parameters. CONCLUSIONS: Urine Ach is higher in responders to anti-cholinergic therapy, and urine cholinergic metabolites were higher in the UUI patients compared to controls.

Adoption, Safety, and Retreatment Rates of Prostatic Urethral Lift for Benign Prostatic Enlargement.

PURPOSE: Novel minimally invasive therapies like the prostatic urethral lift are among the many endoscopic options for the treatment of benign prostatic enlargement and lower urinary tract symptoms (BPE/LUTS). To further understand the relative uptake, complications and retreatment rates of contemporary endoscopic procedures for BPE/LUTS across diverse practice types, we performed a retrospective study of inpatient and ambulatory surgery encounters in the Premier Healthcare database. MATERIALS AND METHODS: We included men who underwent endoscopic procedures for BPE/LUTS between 2000 and 2018. We determined the utilization of endoscopic therapies for BPE/LUTS, 30-day and 90-day readmission rates, and retreatment rate. Multivariable logistic regression was used to assess the association of procedure type with outcomes for the 3 most commonly performed procedures. RESULTS: We identified 175,150 men treated with endoscopic surgery for BPE/LUTS. The annual percent utilization of the prostatic urethral lift increased from <1% in 2014 to 10.4% in 2018. Compared to transurethral resection of the prostate and prostate photovaporization, prostatic urethral lift was associated with a lower odds of readmission at 30 (OR 0.58, p <0.01) and 90 (OR 0.55, p <0.01) days and a higher odds of retreatment within 2 years of followup (OR 1.78, p <0.01). CONCLUSIONS: Providers have rapidly adopted prostatic urethral lift which accounted for more than 1 in 10 endoscopic procedures captured for BPE/LUTS in 2018. Men treated with prostatic urethral lift are readmitted less within 30 and 90 days but are more likely to be retreated within 2 years of their index procedure as compared to men treated with transurethral resection of the prostate or prostate photovaporization.

Tamsulosin vs placebo to prevent postoperative urinary retention following female pelvic reconstructive surgery: a multicenter randomized controlled trial.

BACKGROUND: Postoperative urinary retention is common after female pelvic reconstructive surgery. Alpha receptor antagonists can improve dysfunctional voiding by relaxing the bladder outlet and may be effective in reducing the risk of postoperative urinary retention. OBJECTIVE: This study aimed to determine whether tamsulosin is effective in preventing postoperative urinary retention in women undergoing surgery for pelvic organ prolapse. STUDY DESIGN: This was a multicenter, double-blind, randomized controlled trial between August 2018 and June 2020, including women undergoing surgery for pelvic organ prolapse. Patients were excluded from recruitment if they had elevated preoperative postvoid residual volume, history of postoperative urinary retention, or a contraindication to tamsulosin. Those who experienced cystotomy were excluded from analysis. Participants were randomized to a 10-day perioperative course of tamsulosin 0.4 mg vs placebo, beginning 3 days before surgery. A standardized voiding trial was performed on postoperative day 1. The primary outcome was the development of postoperative urinary retention, as defined by the failure of the voiding trial or subsequent need for catheterization to empty the bladder. Secondary outcomes included the rate of urinary tract infection and the impact on lower urinary tract symptoms as measured by the American Urological Association Symptom Index. RESULTS: Of 119 patients, 57 received tamsulosin and 62 received placebo. Groups were similar in regard to demographics, preoperative prolapse and voiding characteristics, and surgical details. Tamsulosin was associated with a lower rate of postoperative urinary retention than placebo (5 patients [8.8%] vs 16 patients [25.8%]; odds ratio, 0.28; 95% confidence interval, 0.09-81; P=.02). The number needed to treat to prevent 1 case of postoperative urinary retention was 5.9 patients. The rate of urinary tract infection did not differ between groups. American Urological Association Symptom Index scores significantly improved after surgery in both groups (median total score, 14 vs 7; P<.01). Scores related to urinary stream improved more in the tamsulosin group than in placebo (P=.03). CONCLUSION: In this placebo-controlled trial, tamsulosin use was associated with a reduced risk of postoperative urinary retention in women undergoing surgery for pelvic organ prolapse.

Physical multimorbidity and incident urinary incontinence among community-dwelling adults aged ≥50 years: findings from a prospective analysis of the Irish Longitudinal Study on Ageing.

BACKGROUND: There are no prospective studies on the association between multimorbidity and urinary incontinence (UI), while mediators in this association are unknown. Thus, we aimed to (i) investigate the longitudinal association between multimorbidity and UI in a large sample of Irish adults aged ≥50 years and (ii) investigate to what extent physical activity, polypharmacy, cognitive function, sleep problems, handgrip strength and disability mediate the association. METHODS: Data on 5,946 adults aged ≥50 years old from the Irish Longitudinal Study on Aging were analysed. The baseline survey was conducted between 2009 and 2011 and follow-up after 2 years was conducted. Information on self-reported occurrence of UI in the past 12 months and lifetime diagnosis of 14 chronic conditions were obtained. Multivariable logistic regression and mediation analysis were conducted. RESULTS: After adjustment for potential confounders, compared to having no chronic conditions at baseline, having three (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.30-2.48) and four or more (OR = 1.86; 95% CI = 1.32-2.60), chronic conditions were significantly associated with incident UI. Mediation analysis showed that polypharmacy, sleep problems and disability explained 22.7, 17.8 and 14.7% of the association between multimorbidity (i.e. two or more chronic conditions) and incident UI, respectively. CONCLUSION: A greater number of chronic conditions at baseline were associated with a higher risk for incident UI at 2-year follow-up among adults aged ≥50 years in Ireland. Considering the effects of different medications on UI and improving sleep quality and disability among people aged ≥50 years with multimorbidity may reduce the incidence of UI.

Abdominal and vaginal pelvic support with concomitant hysterectomy for uterovaginal pelvic prolapse: a comparative systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: While approximately 225,000 pelvic organ prolapse (POP) surgeries are performed annually in the US, there is no consensus on the optimal route for pelvic support for the initial treatment of uterovaginal prolapse (UVP). Our objective is to compare the outcomes of abdominal sacrocolpopexy (ASC) to vaginal pelvic support (VPS) with either uterosacral ligament suspension (USLS) or sacrospinous ligament fixation (SSF) in combination with hysterectomy for treating apical prolapse. METHODS: A systematic search was performed through March 2021. Studies comparing ASC with VPS for treatment of UVP were included in the review. The primary outcome was the rate of overall anatomic prolapse failure per studies' definition. Secondary outcomes included evaluating isolated recurrent vaginal wall prolapse, postoperative POP-Q points, total vaginal length (TVL), and Pelvic Floor Distress Inventory (PFDI-20) scores. Random effect analyses were generated utilizing R 4.0.2. RESULTS: Out of 4225 total studies, 4 met our inclusion criteria, including 226 patients in the ASC group and 199 patients in the VPS group. ASC was not found to be associated with a higher rate of vaginal wall prolapse recurrence (OR = 0.6; 95% CI = 0.2-2.4; P = 0.33). There was no significant difference between groups for anterior or apical vaginal wall prolapse recurrence (P = 0.58 and P = 0.97, respectively). ASC was associated with significantly longer TVL (mean difference [MD]: 1.01; 95% CI = 0.33-1.70; P = 0.02) and better POP-Q Ba scores [MD = -0.23; 95% CI = -0.37; -0.10; P = 0.01]. CONCLUSIONS: ASC and vaginal pelvic support (either USLS or SSF) have comparable anatomical outcomes. However, weak evidence of a difference in TVL and Ba was found. The strength of the evidence in this study is based on the small number of observational studies. A large, randomized trial is highly warranted.

Evaluation of the ACS NSQIP surgical risk calculator in patients undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to evaluate the accuracy of the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) surgical risk calculator in predicting postoperative complications in patients undergoing pelvic organ prolapse surgery. METHODS: We performed a retrospective review of 354 patients who underwent surgery for pelvic organ prolapse from 2013 to 2017 at a single academic institution. Patient medical information and surgical procedure were entered into the calculator to obtain predicted complication rates, which were compared with observed complications. Logistic regression, C-statistic, and Brier score were used to assess the accuracy of the calculator. RESULTS: Of 354 patients included in the analysis, 79.7% were under the age of 75, and 41.5% were classified as American Society of Anesthesiologists class ≥3. The majority of patients underwent robotic sacrocolpopexy (40.7%) or uterosacral ligament suspension (36.4%), followed by colpocleisis, abdominal sacrocolpopexy, and extraperitoneal suspension. Complications were experienced by 100 patients (28.3%). Most common complications were urinary tract infection (n = 57), surgical site infection (n = 42), and readmission (n = 16); other complications were rare. The surgical risk calculator displayed poor predictive ability for experiencing a complication (C-statistic = 0.547, Brier score = 0.25). CONCLUSIONS: The NSQIP surgical risk calculator displayed poor predictive ability in our cohort of patients undergoing surgery for pelvic organ prolapse, suggesting that this tool might have limited clinical applicability to individual patients in this population.

Adnexectomy at the time of vaginal hysterectomy for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Preoperative counseling about salpingectomy with pelvic surgery is recommended by the American College of Obstetrics and Gynecology for ovarian cancer risk reduction. Our objective was to determine recent practice patterns and patient factors associated with salpingectomy with vaginal hysterectomy (VH) for pelvic organ prolapse (POP) in the USA. We hypothesize that salpingectomy might have become more common in recent years. METHODS: We queried the 2014-2016 National Surgical Quality Improvement Program database for women with a postoperative diagnosis of POP who underwent VH with any combination of pelvic reconstructive procedures. CPT codes do not differentiate salpingectomy from salpingo-oophorectomy, so subjects were stratified by whether concurrent adnexectomy was performed. Chi-squared and multivariate logistic regression analyses were used to evaluate characteristics associated with adnexectomy. Propensity score matching was utilized when evaluating postoperative complication rates. RESULTS: Of 5,344 women who underwent VH, 2019 (37.8%) had adnexectomy. Adnexectomy rate increased from 34.4% in 2014 to 46.8% in 2016 (p < 0.001). Adnexectomy rates of fellowship-trained urogynecologists and general gynecologists were similar (36.0% vs 38.8%, p = 0.197). On logistic regression analysis, patients more likely to undergo adnexectomy were < 65 years old (OR 0.844, CI 0.75-0.95, p = 0.004), had BMI <30 (OR 0.76, CI 0.68-0.86, p < 0.001), and were non-smokers (OR 0.78, CI 0.64-0.95, p = 0.016). Mean operative time was 17 min longer with adnexectomy (145 vs 128 min, p < 0.001). There were no differences in postoperative complications or reoperation rates between groups. CONCLUSIONS: Adnexectomy during VH for POP is safe and increasingly utilized by gynecology surgeons in the USA.

Stromal derived factor-1 plasmid as a novel injection for treatment of stress urinary incontinence in a rat model.

INTRODUCTION AND HYPOTHESIS: SDF-1 chemokine enhances tissue regeneration through stem cell chemotaxis, neovascularization and neuronal regeneration. We hypothesized that non-viral delivery of human plasmids that express SDF-1 (pSDF-1) may represent a novel regenerative therapy for stress urinary incontinence (SUI). METHODS: Seventy-six female rats underwent vaginal distention (VD). They were then divided into four groups according to treatment: pSDF-1 (n = 42), sham (n = 30), PBS (n = 1) and luciferase-tagged pSDF-1 (n = 3). Immediately after VD, the pSDF-1 group underwent immediate periurethral injection of pSDF-1, and the sham group received a vehicle injection followed by leak point pressure (LPP) measurement at the 4th, 7th and 14th days. Urogenital tissues were collected for histology. H&E and trichrome slides were analyzed for vascularity and collagen/muscle components of the sphincter. For the luciferase-tagged pSDF-1 group, bioluminescence scans (BLIs) were obtained on the 3rd, 7th and 14th days following injections. Statistical analysis was conducted using ANOVA with post hoc LSD tests. The Mann-Whitney U test was employed to make pair-wise comparisons between the treated and sham groups. We used IBM SPSS, version 22, for statistical analyses. RESULTS: BLI showed high expression of luciferase-tagged pSDF-1 in the pelvic area over time. VD resulted in a decline of LPP at the 4th day in both groups. The pSDF1-treated group demonstrated accelerated recovery that was significantly higher than that of the sham-treated group at the 7th day (22.64 cmH2O versus 13.99 cmH2O, p < 0.001). Functional improvement persisted until the 14th day (30.51 cmH2O versus 24.11 cmH2O, p = 0.067). Vascularity density in the pSDF-1-treated group was higher than in the sham group at the 7th and 14th days (p < 0.05). The muscle density/sphincter area increased significantly from the 4th to 14th day only in the pSDF-1 group. CONCLUSIONS: Periurethral injection of pSDF-1 after simulated childbirth accelerated the recovery of continence and regeneration of the urethral sphincter in a rat SUI model. This intervention can potentially be translated to the treatment of post-partum urinary incontinence.