Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome.

Postmenopausal women are severely affected by recurrent urinary tract infection (rUTI). The urogenital microbiome is a key component of the urinary environment. However, changes in the urogenital microbiome underlying rUTI susceptibility are unknown. Here, we perform shotgun metagenomics and advanced culture on urine from a controlled cohort of postmenopausal women to identify urogenital microbiome compositional and function changes linked to rUTI susceptibility. We identify candidate taxonomic biomarkers of rUTI susceptibility in postmenopausal women and an enrichment of lactobacilli in postmenopausal women taking estrogen hormone therapy. We find robust correlations between Bifidobacterium and Lactobacillus and urinary estrogens in women without urinary tract infection (UTI) history. Functional analyses reveal distinct metabolic and antimicrobial resistance gene (ARG) signatures associated with rUTI. Importantly, we find that ARGs are enriched in the urogenital microbiomes of women with rUTI history independent of current UTI status. Our data suggest that rUTI and estrogen shape the urogenital microbiome in postmenopausal women.

Reduced urothelial expression of uroplakin-IIIa in cystitis areas in bladders of postmenopausal women with recurrent urinary tract infections: pilot study.

PURPOSE: To study human bladder biopsies to investigate urothelial response to UTI, expression of uroplakin, and urothelial response after healing from cystoscopy with electrofulguration (CEF) treatment for antibiotic-recalcitrant RUTI. METHODS: Following IRB approval, cold cup bladder biopsies from "no cystitis" and "cystitis" regions were obtained from women with antibiotic-recalcitrant rUTI undergoing CEF under anesthesia. "No cystitis" and "cystitis" biopsies from 14 patients (5 had prior CEF, 9 naïve) were analyzed by immunofluorescence (IF) confocal microscopy using antibodies against uroplakin-IIIa. For an additional 6 patients (2 prior CEF, 4 naïve), only "cystitis" area biopsies were taken and analyzed. Cytokeratin 5 (marker for squamous metaplasia) staining was performed on 14 patients. RESULTS: In healthy tissue, uroplakin-IIIa staining was observed as a contiguous line on the luminal surface of umbrella cells. In "cystitis" areas for 19/20 patients, there was either no uroplakin-IIIa staining observed or spotty (+) staining. The "cystitis" regions of all patients had less intense uroplakin-IIIa staining compared to the matched "no cystitis" area in the same patient. In patients post-CEF but requiring repeat EF for persistent RUTI lesions, healed areas served as control and in 3 of 7 patients no uroplakin-IIIa staining was observed. Squamous metaplasia was observed in 10 patients. CONCLUSION: In bladders of postmenopausal women with antibiotic-recalcitrant RUTI, areas with visible cystitis expressed less uroplakin-IIIa, supporting the model of urothelial exfoliation in response to UTI.

Twitter and Instagram Use in the Urology Residency Application Process.

OBJECTIVE: To define urology applicant attitudes and usage trends of social media (SM) during the 2021 urology match cycle. METHODS: We emailed an anonymous, de-identified 22-question, multiple choice survey to all applicants to our institution for the 2021 Urology Residency Match. We asked participants about use of SM and which aspects they found useful in the application process. Univariate descriptive analyses were conducted based on survey responses. Chi-square analyses were performed to define significant differences in use of social media and resultant match outcomes. RESULTS: Of the 528 students who registered for the 2021 AUA Match, 398 received our survey (75%), and 144 responded (27% of applicants nationwide). Of survey participants, 49% made a new account on Twitter while 30% had a preexisting account. Most participants (71%) had a preexisting Instagram account, while only 3% made a new account. Most participants agreed Twitter was used as a source to gather information about programs (84%) and learn about events (89%). Participants found SM most helpful for announcing event dates (71%) and highlighting resident social life (59%). Applicants did not match more highly on their rank lists if they used Twitter (P = .427) or Instagram (P = .166) and were not more likely to get more interviews if they used Twitter (P = .246) or Instagram (P = .114) CONCLUSION: Applicants found Twitter to be an important source of information through the virtual interview process. Despite the use of SM by most applicants, published content did not impact rank list decisions nor did SM engagement predict match outcomes.

The Virtual Urology Residency Match Process: Moving Beyond the Pandemic.

OBJECTIVES: To define applicant response to the 2021 Urology Residency Match Process in the COVID-19 Pandemic and to extrapolate lessons to optimize the urology resident selection process after the pandemic. METHODS: We emailed an anonymous, de-identified 22-question, multiple choice survey to all applicants to our institution for the 2021 Urology Residency Match, including a summary of the study with a survey link (RedCap). RESULTS: Of the 398 survey recipients, 144 responded (36%). Even if the match process were not limited by COVID-19, 39% of applicants thought interviews should remain in virtual format, 23% said "no," and 30% said "not sure." Nearly all applicants (97%) thought all interview offers should be released on the same day. Regarding the early match, 84% thought this should remain. When asked what factors had the most impact on rank lists, faculty and resident interviews were overwhelmingly favored. Open houses and resident "happy hours" were less important. Most applicants agreed that the faculty and resident interviews and informational talks were adequately replicated on the virtual platform. A majority of applicants (65%) spent under $2000 for the application cycle. CONCLUSION: The COVID-19 pandemic dramatically changed the urology match process. The faculty and resident interviews remained the most important factors in program ranking, and most applicants agreed those were adequately replicated in the virtual format. A plurality of applicants felt that the interview process should remain virtual in a post-COVID-19 environment. The virtual application cycle reduced the cost of applying to residency.

Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women.

Urinary tract infection (UTI) is one of the most common adult bacterial infections and exhibits high recurrence rates, especially in postmenopausal women. Studies in mouse models suggest that cyclooxygenase-2 (COX-2)-mediated inflammation sensitizes the bladder to recurrent UTI (rUTI). However, COX-2-mediated inflammation has not been robustly studied in human rUTI. We used human cohorts to assess urothelial COX-2 production and evaluate its product, PGE2, as a biomarker for rUTI in postmenopausal women. We found that the percentage of COX-2-positive cells was elevated in inflamed versus uninflamed bladder regions. We analyzed the performance of urinary PGE2 as a biomarker for rUTI in a controlled cohort of 92 postmenopausal women and PGE2 consistently outperformed all other tested clinical variables as a predictor of rUTI status. Furthermore, time-to-relapse analysis indicated that the risk of rUTI relapse was 3.6 times higher in women with above median urinary PGE2 levels than with below median levels. Taken together, these data suggest that urinary PGE2 may be a clinically useful diagnostic and prognostic biomarker for rUTI in postmenopausal women.

A standardized telephone interview with validated questionnaires for very long-term evaluation of women lost to follow-up after a stress urinary incontinence procedure.

OBJECTIVES: Telephone interviews including questionnaires have been used to obtain very long-term (>10-year) follow-up after stress urinary incontinence (SUI) procedures in women otherwise lost to follow-up (LTF). For questionnaires validated for office use, our goal was to evaluate recent telephone vs last clinic scores in a long-term study. METHODS: For women with >10 years of follow-up after anterior vaginal wall suspension (AVWS) for bothersome SUI associated with an anterior compartment prolapse, questionnaire scores from their last clinic encounter were compared with their scores from a standardized telephone interview at long-term follow-up. The validated questionnaires were Urinary Distress Inventory 6-Short Form (UDI-6), International Incontinence Questionnaire 7-Short Form (IIQ-7), and Quality of Life (QoL). RESULTS: Eighty-four women underwent a telephone interview (median follow-up: 13.8 years, interquartile range [IQR]: 12.2-17) after AVWS. The median difference between telephone and clinic visit was 10.2 years (IQR: 6.1-12.2). The clinic UDI-6 total score remained low but was higher than the phone score (mean difference 1.2, P = .0023). The UDI-6 Q2, Q3, Q5, IIQ-7, and QoL scores did not significantly differ between clinic and phone. For "incontinent" AVWS patients (UDI-6 Q3 ≥ 2), there was a larger difference between clinic and phone UDI-6 total score (P < .0001), while "dry" patients (UDI-6 Q3 ≤ 1) responded similarly. CONCLUSIONS: In women who would otherwise be LTF after anti-incontinence native tissue repair AVWS, UDI-6 total score varied slightly between last clinic and long-term follow-up phone interviews, but QoL and IIQ-7 remained similar.

Assessing the Female and Underrepresented Minority Medical Student Experience in the Urology Match: Where Do We Fall Short?

OBJECTIVE: To better understand the experiences of female and underrepresented minority (URM) medical students pursuing urology and determine if discrimination was perceived at any point during the application process. METHODS: After the rank list submission deadline (January 2, 2020), we emailed an anonymous survey to all 353 applicants to our institution for the 2020 AUA Residency Match (80.0% of applicants nationally). The survey inquired about their experiences pursuing urology and the residency match process. Ordinal regression models were used to identify any significant predictors of survey responses. RESULTS: One hundred ninety applicants (136 male [72%], 54 female [28%]) completed the survey. A significantly higher percentage of females vs males noted discrimination (odds ratio: 2.53; confidence interval: 1.37-4.74, Fig. 1). URM students also reported higher frequencies of discrimination than non-URM students (odds ratio: 2.27; confidence interval: 1.07-4.83). Thirty-two percent of respondents tested positive on the Maslach Burnout Inventory; we did not identify any predictors of burnout. Higher proportions of female residents, faculty and leadership at a particular program had a more favorable impact on the rank lists of female applicants compared with males. Higher proportions of URM residents, faculty and leadership at a particular program had a more favorable impact on the rank lists of URM applicants compared with non-URM. CONCLUSION: Our collective findings suggest that URM and female medical students have less favorable experiences interacting with urology trainees and faculty than do their nonminority and male counterparts. Higher percentages of female and URM urology residents and faculty promote effective recruitment of female and URM applicants.

Very long-term follow-up of the anterior vaginal wall suspension procedure for incontinence and/or prolapse repair.

OBJECTIVE: To report outcomes of the anterior vaginal wall suspension (AVWS) procedure for stress urinary incontinence (SUI) and/or anterior compartment prolapse (POP), with minimum 10-year follow-up. METHODS: Following institutional review board approval, a database of patients with > 10-year follow-up after AVWS for bothersome SUI with early stage anterior compartment prolapse (stage ≤ 2) or symptomatic anterior compartment prolapse (stage > 2) was reviewed. Preoperative evaluation included validated questionnaires [Urogenital Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), quality of life (QoL)], Pelvic Organ Prolapse Quantification (POP-Q), and voiding cystourethrography. Follow-up data was based on clinic visits or telephone interviews for patients not seen in the past 2 years. Telephone interviews used validated questionnaires and were conducted by a third party not involved in patient care. Failure was defined as reoperation for SUI or POP. The influence of lost to follow-up (LTF) was also analyzed. RESULTS: Between 1996 and 2008, 161 of 328 patients met study criteria, with follow-up from phone interviews (103) or clinic visits (58). The LTF patients were deceased (52), mentally disabled (5), or unreachable by telephone (110). Median follow-up was 13.5 years (IQR 11.5-17). Type of follow-up (clinic vs. phone) and uterine status (concomitant/prior/no hysterectomy) did not impact reoperation rates. Reoperation occurred in 23/161 (14%) and consisted of sacrocolpopexy (8), anterior colporrhaphy (5), injectable agents (8), fascial sling (2). CONCLUSIONS: The AVWS procedure to restore anterior vaginal support to the bladder neck and bladder base to correct SUI/POP can provide satisfactory and durable results.

Prospective Evaluation of Daily and Weekly Urine pH Variations Along With Diet Intake in Postmenopausal Women With Recurrent Urinary Tract Infections.

OBJECTIVES: Acidic urine pH may be protective against recurrent urinary tract infections (RUTIs). After reviewing the literature, we primarily analyzed urine pH fluctuations and secondarily compared them with diet in older women with RUTIs. METHODS: After IRB approval, postmenopausal women with documented RUTIs were enrolled. Participants were given preformatted charts to record urinalysis reagent strips (Medimpex) findings 4 times per day and concomitant food/beverage intake (food diary). Urine cultures at baseline ensured no infection during measurement period. Nutrient content reported in food diaries was analyzed by an experienced registered dietitian and compared with parallel fluctuations in urine pH. RESULTS: Of 26 women with median age of 72 years (55-86 years), the first 3 days of diet and urine pH recordings found that 17 (65%) of 26 exhibited urine pH variation greater than 1 unit, with an overall median of 6 (5-9). Comparing dietary analysis and urine pH changes, beta-carotene (P = 0.017) and total dietary sugar intake (P = 0.036) were associated with a decrease in urine pH, whereas monounsaturated fatty acids (MFA, 22:1, P = 0.023) and protein (P = 0.028) were associated with an increase in urine pH. CONCLUSIONS: In this real-life, observational study, 65% of older women with RUTIs exhibited notable changes in urine pH, with decreased urine pH associated with nutrients found in orange and yellow vegetables and several major food groups. A longitudinal study is needed to determine if changing an individual's diet and/or adding supplements could decrease the urine pH, thus affecting the rate of RUTIs.

Durability of Macroplastique volume and configuration in women with stress urinary incontinence secondary to intrinsic sphincter deficiency: A retrospective review.

OBJECTIVES: To evaluate the durability of Macroplastique® (MPQ) volume and configuration in women with stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD) using serial three-dimensional ultrasound (3DUS) measurements. METHODS: Following Institutional Review Board approval, charts of women with SUI and ISD (defined based on leak point pressure; lateral imaging of urethral support without hypermobility) who underwent MPQ were reviewed from a prospectively maintained database. All had at least two serial transperineal 3DUS measurements with no MPQ or other bulking agent injection between measurements. 3DUS was performed using the Philips IU22 ultrasound system with endovaginal 3D 9-3V end-fire probe typically at 6-8 weeks post-injection and yearly thereafter. The same imaging team blinded to clinical outcomes evaluated volume and configuration (circumferential/symmetric or asymmetric) at each 3DUS. RESULTS: Between 2011 and 2019, 62 of 174 women met study criteria. Those with prior other bulking agent injection or having ≤1 3DUS follow-up were excluded. Seventy-one percent of patients had one injection, while the remainder had two or more (29%). Median time between first and second 3DUS was 12 months. The mean change in MPQ volume between the first and last 3DUS measurement was -0.2 cc (95% CI: -0.5 to 0.004; P = .054). A median of 5.0 cc were injected in each patient. Forty-seven women had symmetric MPQ at first 3DUS, of whom only five (11%) had a follow-up 3DUS showing asymmetric MPQ distribution. CONCLUSIONS: At mid-term follow-up, repeat transperineal 3DUS after MPQ injection revealed minimal change in volume and configuration in the urethral wall.

Urology Residency Applications in the COVID-19 Era.

OBJECTIVE: To evaluate urology applicants' opinions about the interview process during the COVID-19 pandemic. MATERIAL AND METHODS: An anonymous survey was emailed to applicants to our institution from the 2019 and 2020 urology matches prior to issuance of professional organization guidelines. The survey inquired about attitudes toward the residency interview process in the era of COVID-19 and which interview elements could be replicated virtually. Descriptive statistics were utilized. RESULTS: Eighty percent of urology applicants from the 2019 and 2020 matches received our survey. One hundred fifty-six people (24% of recipients) responded. Thirty-four percent preferred virtual interviews, while 41% in-person interviews at each program, and 25% regional/centralized interviews. Sixty-four percent said that interactions with residents (pre/postinterview social and informal time) were the most important interview day component and 81% said it could not be replicated virtually. Conversely, 81% believed faculty interviews could be replicated virtually. Eighty-seven percent believed that city visits could not be accomplished virtually. A plurality felt that away rotations and second-looks should be allowed (both 45%). COMMENT: Applicants feel that faculty interviews can be replicated virtually, while resident interactions cannot. Steps such as a low-stakes second looks after programs submit rank lists (potentially extending this window) and small virtual encounters with residents could ease applicant concerns. CONCLUSION: Applicants have concerns about changes to the match processes. Programs can adopt virtual best practices to address these issues.

Challenges of Very Long-term Reporting in Stress Urinary Incontinence Surgeries in Women.

OBJECTIVE: To review studies on surgeries to correct stress urinary incontinence (SUI) with very long-term results (≥ 10 years) to explore the challenges in reporting long-term follow-up. METHODS: A comprehensive Ovid and PubMed search was conducted for articles containing long-term data over 10 years for the most commonly established surgical procedures to correct SUI. The methods of follow-up, lost to follow-up (LTF) rates, cure rates, and complications were compared. RESULTS: SUI corrective surgeries reviewed included: tension free vaginal tape, transobturator sling, retropubic suspensions (Burch, Marshall-Marchetti-Krantz), autologous fascial sling, and Stamey needle suspension. Mean follow-up of all 17 studies was 12.6 years (range: 10-17 years) with sample sizes ranging from 26 to 650 patients. Methods of follow-up included clinic visits (n = 11), telephone interviews (n = 8), or mailed questionnaires (n = 5). Mean LTF rate was 24% (range: 10-49%). Mean objective and subjective cure rate with varying success definitions was 86% (range 81-91%) and 69%, respectively (range: 33-94%). The most common complications included de novo urgency (range: 2-70%), repeat SUI/prolapse surgeries (range: 2-37%), mesh/suture exposure (range: 1-9%), voiding problems (range: 2-36%), and pain (range: 2-14%). CONCLUSION: All very long-term data for SUI surgeries share considerable LTF, infrequent examination data, mostly questionnaire-based information, and variable success rates from varying success definitions. Standardization of all these key outcome measures is urgently needed to provide more reliable long-term information on the outcome of these procedures.

Long-Term Results of Burch and Autologous Sling Procedures for Stress Urinary Incontinence in E-SISTEr Participants at 1 Site.

PURPOSE: We report long-term outcomes in participants in the E-SISTEr (Extended Stress Incontinence Surgical Treatment Efficacy Trial) at 1 tertiary care center who underwent a Burch or a fascial sling procedure for stress urinary incontinence. MATERIALS AND METHODS: After receiving institutional review board approval E-SISTEr participants at 1 center who underwent midterm office evaluation in 2010 were further reevaluated at longer term followup by office visits and structured telephone interviews. The telephone interviews were performed by a third party not involved in patient care for those not seen in the last 2 years. Each group received validated questionnaires, including the UDI-6 (Urogenital Distress Inventory-Short Form), the IIQ-7 (Incontinence Impact Questionnaire-Short Form) and the visual analogue quality of life score questionnaire. Failure was measured by Kaplan-Meier curves using time to reoperation for stress urinary incontinence. RESULTS: Of the 29 eligible patients, including 14 treated with a Burch procedure and 15 treated with a sling procedure, 21 had long-term information available, including 11 and 10, respectively. Median followup was 15.1 years (range 11.2 to 16.0). One of the 8 patients was lost to followup, 1 died and 7 were unreachable by telephone. The UDI-6 question 3 score was lower for the 13 patients followed by telephone, including 13 and 7 with a Burch and a sling procedure compared to the 8 seen in clinic, including 5 and 3 with a Burch and a sling procedure, respectively (mean ± SD score 0.3 ± 0.6 vs 1.3 ± 1.1, p=0.0208). The UDI-6 scores were similar for the 2 procedures. Stress urinary incontinence reoperation was performed in 3 cases, including placement of a fascial sling in 1 Burch case. The other 2 cases in the Burch and sling groups received an injectable agent at 11.6 and 13.5 years, respectively. The overall Kaplan-Meier 15-year reoperation-free survival rate was 85.2% (95% CI 60.8-95). CONCLUSIONS: In this well characterized cohort with a median followup of 15.1 years there was sustained improvement in continence scores and quality of life related to stress urinary incontinence in each group and the reoperation rate was low.

Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection.

Urinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. The molecular basis of RUTI, especially in postmenopausal women, has remained unclear because modeling RUTI in mice is difficult, and human data are limited. Invasion of the urothelium and induction of host inflammation are hypothesized to be key mechanisms by which bacterial pathogens cause RUTI. To further our understanding of RUTI in humans, we performed a systematic analysis of urine and bladder biopsy samples from postmenopausal women undergoing cystoscopy with fulguration of trigonitis in the advanced management of antibiotic-refractory RUTI. We provide direct evidence that bacteria reside in the bladder wall of postmenopausal RUTI patients and that diverse bacterial species can be isolated from the bladder tissue. Histopathological scoring revealed significant edema and alterations of urothelial architecture in RUTI patient biopsies. Lymphocytes, including plasma B-cells, were detected within the mesenchyme, urothelium, and follicular aggregates in the majority of patients, indicating that the local adaptive immune response is active during human RUTI. These data provide conclusive evidence that bacteria invade the human urothelium and suggest that diverse bacterial species and the adaptive immune response play important roles in RUTI in humans.