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Parker RM Kenee,1 Alana L Christie,2 Philippe E Zimmern1 1Department of Urology, UT Southwestern Medical Center, Dallas, TX, 75290-9110, USA; 2Simmons Comprehensive Cancer Center Biostatistics, UT Southwestern Medical Center, Dallas, TX, 75390-8852, USACorrespondence: Philippe E Zimmern, Department of Urology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9110, USA, Tel +1 214 648 9397, Fax +1 214 648 8786, Email Philippe.Zimmern@UTSouthwestern.eduPurpose: To assess patient reliance on various over-the-counter (OTC) modalities used for prevention of recurrent urinary tract infection (RUTI) after electrofulguration (EF).Patients and Methods: Following IRB approval, qualifying women were offered a short survey over the phone by a medical researcher to collect information about their use of various OTC modalities for prophylaxis of RUTI. Data was compared between two cohorts, ≥ 70 years old and < 70 years old, using chi-squared and Student’s t-tests.Results: From a database of 324 patients, 163 accepted the interview. 17% (28/163) reported current use of cranberry supplements, 10% (16/163) D-mannose supplements, and 42% (69/163) another non-prescription modality for RUTI prophylaxis. The non-geriatric (< 70 years old) cohort spent, on average, $80 less annually on cranberry/D-mannose supplements (P=0.043) than the geriatric cohort and were more likely to use non-prescription modalities for the prevention of UTI (52% vs 30%; P=0.0061). Individuals using D-mannose were also much more likely to purchase their product online compared to those using cranberry supplements (85% vs 56%). Across all modalities, the perceived benefit difference in reducing UTI/year ranged from a median of 0 for Pyridium® (phenazopyridine hydrochloride) to four for probiotics, with D-mannose and cranberry at two/year, and those increasing daily fluid consumption at 2.5 fewer UTI/year.Conclusion: Continued use of non-prescription modalities for RUTI prophylaxis were common among women with an EF history, but varied based on age groups. Across both age cohorts, annual expenditure and perceived benefit also varied among different OTC prophylactic modalities. Awareness of type and method of OTC modality implementation by patients with RUTI is essential to aligning use with current field recommendations.Keywords: recurrent UTI, menopausal women, cranberry, D-mannose, UTI supplements

Objective: Stress urinary incontinence (SUI) affects a third of the female population and is characterized by involuntary urine leakage during abdominal efforts such as sneezing, laughing, or coughing. Acute neuromodulation of the bulbospongiosus nerve (BsN) was shown to increase bladder efficiency in aged and multiparous rabbits. This study investigates the efficacy of sub-chronic BsN neuromodulation in alleviating SUI-like deficits in mature multiparous rabbits, characterized by increased urine leakage and reduced leak point pressure. Results: Using the voiding spot assay, we observed a 40% reduction in urine leakage events after 30 days of BsN stimulation, which correlated with a 60% increase in daily micturition volume, a 10-fold increase in voided volume, and improvements in voiding efficiency and leak point pressure compared to negative control animals. Conclusion: In multiparous rabbits, BsN neuromodulation improves important SUI-like metrics including bladder capacity and urethral closure, supporting the use of this bioelectronic modality as treatment for SUI.

The corona mortis is a variant vascular anastomosis that crosses behind the superior pubic ramus connecting the external and internal iliac vessels. Its location with respect to key landmarks in the retropubic space varies. This case demonstrates a life-threatening hemorrhage following an anterior vaginal wall suspension due to needle passer injury of the corona mortis successfully managed with endovascular embolization. Surgeons operating in the retropubic space need to be cognizant of this vascular variant and potential for significant bleeding when injured. Prompt vascular control either endovascularly or with open exploration is critical in preventing patient mortality.

Macroplastique® is a periurethral bulking agent used for the treatment of female stress urinary incontinence. It is composed of polydimethylsiloxane macroparticles suspended in a polyvinylpyrolidone carrier to allow injection. The patient in this case report had increased 18F-FDG avidity on PET scan at the site of prior Macroplastique® injection. This avidity was likely due to a local inflammatory response and did not represent an occult malignancy. Keen clinical judgement is necessary when this PET-avid area is demonstrated in women with prior bulking therapy as this is an incidental benign finding that does not require further invasive management.

Introduction and Objectives: Relevant, meaningful, and achievable data points are critical in objectively assessing quality, utility, and outcomes in female stress urinary incontinence (SUI) surgery. A minimum data set female SUI surgery studies was proposed by the first American Urological Association guidelines on the surgical management of female SUI in 1997, but recommendation adherence has been suboptimal The Female Stress Urinary Incontinence Surgical Publication Working Group (WG) was created from members of several prominent organizations to formulate a recommended standard of study structure, description, and minimum outcome data set to be utilized in designing and publishing future SUI studies. The goal of this WG was to create a body of evidence better able to assess the outcomes of female SUI surgery. Methods: The WG reviewed the minimum data set proposed in the 1997 AUA SUI Guideline document, and other relevant literature. The body of literature was examined in the context of the profound changes in the field over the past 25 years. Through a DELPHI process, a standard study structure and minimum data set were generated. Care was taken to balance the value of several meaningful and relevant data points against the burden of creating an excessively difficult or restrictive standard that would disincentivize widespread adoption and negatively impact manuscript production and acceptance. Results:: The WG outlined standardization in four major areas: (1) study design, (2) pretreatment demographics and characterization of the study population, (3) intraoperative events, and (4) post-treatment evaluation, and complications. Forty-two items were evaluated and graded as: STANDARD — must be included; ADDITIONAL — may be included for a specific study and is inclusive of the Standard items; OPTIMAL — may be included for a comprehensive study and is inclusive of the Standard and Additional items; UNNECESSARY/LEGACY — not relevant. Conclusion:: A reasonable, achievable, and clinically meaningful minimum data set has been constructed. A structured framework will allow future surgical interventions for female SUI to be objectively scrutinized and compared in a clinically significant manner. Ultimately, such a data set, if adopted by the academic community, will enhance the quality of the scientific literature, and ultimately improve short and long-term outcomes for female patients undergoing surgery to correct SUI.

Purpose:: To compare qualify of life outcomes in women with mixed urinary incontinence (MUI), urge (UUI) or stress (SUI) urinary incontinence after treatment with an anterior vaginal wall suspension (AVWS) to correct urethral hypermobility and concomitant anterior compartment prolapse (ACP). Methods:: Following IRB approval, a prospective long-term database of women who underwent an AVWS for urinary incontinence (UI) with early stage (stage ≤2) ACP was reviewed. Patients completed the Urogenital Distress Inventory short form (UDI-6 SF) and a one question visual analog scale (VAS) of quality of life (QoL) before and after AVWS. Indication for AVWS was based on demonstrable UI, with documented urethral hypermobility and cystocele on standing lateral cystogram comparing rest and straining views. Three groups (MUI, SUI, and UUI) were analyzed based on urge (Question 2) and stress (Question 3) predominant scores at baseline. Results:: From 1997 to 2018, 104 patients met study criteria: 54 with MUI, 30 SUI predominant, and 20 UUI predominant. Total UDI-6 and QoL scores improved significantly from baseline to 1-year post-AVWS and to the last visit (median 3.5 years) in all three groups. Patients with MUI had the most improvement based on UDI-6 total and QoL scores. Conclusions:: Regardless of the nature of baseline UI symptoms, restoring support of the anterior vaginal wall compartment can durably improve UI-specific quality of life scores in the short and long-term.

Introduction: We proceeded with an in-depth review of diet diaries for nutrient analysis from a cohort of women suffering from uncomplicated recurrent urinary tract infection (RUTI) to validate the accuracy of our current food diet record (FDR) form and evaluate possible domains of improvement. Materials and Methods: As part of an IRB-approved study, this previously published cohort of NHANES-comparable women was analyzed for consistency of the nutrient intake over 3 days, the influence of the time between meals and urine pH, the effect of nutrient intake over interval time between meals, and seasonal and before/during the COVID-19 pandemic changes. Intrarater reliability for nutrient analysis and intrapatient variability for urine pH were computed to test for consistency. Results: Intrarater reliability for diet analysis was 91% accurate for foods and beverage matching and nutrient analysis. Mean standard deviation of urine pH readings within study participants was 0.4 (95% CI: 0.4, 0.5). An association was noted between total calories and fat consumed at breakfast and an increase in time to lunch. Calories consumed were unaffected across seasons or during the COVID-19 pandemic. Water intake during summer was significantly lower than that during fall and winter (both, p < 0.001). The patients who reported drinking water had a significantly lower average urine pH than women who did not report drinking water (5.8 vs. 6.2; p = 0.026). Conclusion: In this cohort of postmenopausal women with RUTIs, in-depth analysis of our current FDR findings led to several actionable items, which will improve our current food diet self-reporting process by our patients.

ABSTRACT Electrofulguration (EF) of areas of chronic cystitis in women with antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) can result in improvement of their urinary tract infections (UTIs). We compared urine culture (UC) findings in patients before and after EF, as well as how they vary with cystitis stage at the time of EF, to evaluate for persistent species. After obtaining institutional review board approval, we retrospectively reviewed a prospectively maintained database of EF patients for those with positive UC findings in the 3–6 months preceding EF. Patient pre-EF UC was then compared with first positive UC after EF prompted by a new symptomatic UTI episode, with the hypothesis that the same species will be identified before and after EF. Exclusion criteria included UC from outside institution, neurogenic bladder, and need for catheterization. Ninety-nine women with pre- or post-EF UC-recorded organisms met the study criteria. The median age was 65 years (interquartile range 64–74), with a median time to first positive culture following fulguration of 9.7 months. For 26 patients with positive cultures both pre- and post-EF, the same organism was present in both cultures in 73% of the patients, with predominantly Escherichia coli. EF was effective at reducing the rate of UTIs in this population. For women undergoing EF for antibiotic-recalcitrant RUTIs and associated chronic cystitis lesions, 73% of those with a UC obtained at the time of a first symptomatic recurrent UTI episode post-EF expressed the same organism as before EF. Further study is needed to better understand the evolution of the microbiome post-EF.IMPORTANCEAmong women who experience a recurrent urinary tract infection after a fulguration procedure on areas of chronic cystitis in their bladder, there are no data available on whether the bacterial species found in urine cultures are the same or different from those present before fulguration. By removing the inflamed surface layer of cystitis during fulguration, it is possible that the procedure unmasks deep-seated bacteria. The bacterial kingdom in the bladder wall of these chronically infected women may be different from what is expressed sporadically in urine cultures. Confirming prior studies, we found that fulguration in women with antibiotic-recalcitrant recurrent urinary tract infections and cystitis lesions was effective at reducing the rate of urinary tract infections. At the time of a first symptomatic recurrent UTI episode post-fulguration, 73% expressed the same organism in urine culture as before fulguration. Further study is needed to better understand the evolution of the microbiome post-EF. This article evaluates persistent infections after electrofulguration of areas with chronic cystitis in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections. Pre-fulguration urine cultures were compared with the first positive urine culture prompted by a new symptomatic UTI episode after electrofulguration, with the hypothesis that the same species will be identified before and after the fulguration procedure. Electrofulguration was effective at reducing the rate of UTIs in this population. However, 73% of those with a urine culture obtained at the time of a first symptomatic recurrent UTI episode post-electrofulguration expressed the same organism (predominantly Escherichia coli) as before the fulguration procedure. Further study is needed to better understand the evolution of the microbiome after electrofulguration.

ABSTRACTManagement of urinary tract infection (UTI) in postmenopausal women can be challenging. The recent rise in resistance to most of the available oral antibiotic options together with high recurrence rate in postmenopausal women has further complicated treatment of UTI. As such, intravesical instillations of antibiotics like gentamicin are being investigated as an alternative to oral antibiotic therapies. This study evaluates the efficacy of the candidate intravesical therapeutic VesiX, a solution containing the cationic detergent Cetylpyridinium chloride, against a broad range of uropathogenic bacterial species clinically isolated from postmenopausal women with recurrent UTI (rUTI). We also evaluate the cytotoxicity of VesiX against cultured bladder epithelial cells and find that low concentrations of 0.0063% and 0.0125% provide significant bactericidal effect toward diverse bacterial species including uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, and Proteus mirabilis while minimizing cytotoxic effects against cultured 5637 bladder epithelial cells. Lastly, to begin to evaluate the potential utility of using VesiX in combination therapy with existing intravesical therapies for rUTI, we investigate the combined effects of VesiX and the intravesical antibiotic gentamicin. We find that VesiX and gentamicin are not antagonistic and are able to reduce levels of intracellular UPEC in cultured bladder epithelial cells.IMPORTANCEWhen urinary tract infections (UTIs), which affect over 50% of women, become resistant to available antibiotic therapies dangerous complications like kidney infection and lethal sepsis can occur. New therapeutic paradigms are needed to expand our arsenal against these difficult to manage infections. Our study investigates VesiX, a Cetylpyridinium chloride (CPC)-based therapeutic, as a candidate broad-spectrum antimicrobial agent for use in bladder instillation therapy for antibiotic-resistant UTI. CPC is a cationic surfactant that is FDA-approved for use in mouthwashes and is used as a food additive but has not been extensively evaluated as a UTI therapeutic. Our study is the first to investigate its rapid bactericidal kinetics against diverse uropathogenic bacterial species isolated from postmenopausal women with recurrent UTI and host cytotoxicity. We also report that together with the FDA-approved bladder-instillation agent gentamicin, VesiX was able to significantly reduce intracellular populations of uropathogenic bacteria in cultured bladder epithelial cells.

ABSTRACTEnterococcus faecalis is the leading Gram-positive bacterial species implicated in urinary tract infection (UTI). An opportunistic pathogen, E. faecalis is a commensal of the human gastrointestinal tract (GIT), and its presence in the GIT is a predisposing factor for UTI. How E. faecalis colonizes and survives in the urinary tract (UT) is poorly understood, especially in uncomplicated or recurrent UTI. The UT is distinct from the GIT and is characterized by a sparse nutrient landscape and unique environmental stressors. In this study, we isolated and sequenced a collection of 37 clinical E. faecalis strains from the urine of primarily postmenopausal women. We generated 33 closed genome assemblies and 4 highly contiguous draft assemblies and conducted a comparative genomics analysis study to identify genetic features enriched in urinary E. faecalis with respect to E. faecalis isolated from the human GIT and blood. Phylogenetic analysis revealed high diversity among urinary strains and a closer relatedness between urine and gut isolates than blood isolates. Plasmid replicon (rep) typing further underscored possible UT-GIT interconnection, identifying nine shared rep types between urine and gut E. faecalis. Both genotypic and phenotypic analyses of antimicrobial resistance among urinary E. faecalis revealed infrequent resistance to the front-line UTI antibiotics nitrofurantoin and fluoroquinolones and no vancomycin resistance. Finally, comparing gene presence and absence among urinary and gut strains, we identified 19 candidate genes enriched among urinary strains. These genes are involved in the core processes of sugar transport, cobalamin import, glucose metabolism, and post-transcriptional regulation of gene expression.IMPORTANCEUrinary tract infection (UTI) is a global health issue that imposes a substantial burden on healthcare systems. Women are disproportionately affected by UTI, with >60% of women experiencing at least one UTI in their lifetime. UTIs can recur, particularly in postmenopausal women, leading to diminished quality of life and potentially life-threatening complications. Understanding how pathogens colonize and survive in the urinary tract is necessary to identify new therapeutic targets that are urgently needed due to rising rates of antimicrobial resistance. How Enterococcus faecalis, a bacterium commonly associated with UTI, adapts to the urinary tract remains understudied. Here, we generated a collection of high-quality closed genome assemblies of clinical urinary E. faecalis isolated from the urine of postmenopausal women that we used alongside detailed clinical metadata to perform a robust comparative genomic investigation of genetic factors that may be involved in E. faecalis survival in the urinary tract.

BackgroundType 2 diabetes mellitus is considered a risk factor for developing recurrent urinary tract infections. This review examined current knowledge on the incidence rates, bacterial strains, risk factors, treatments, and outcomes of recurrent urinary tract infections in type 2 diabetes, predominantly in women.MethodsA systematic review was conducted for all English language articles from inception to June 2022 utilizing the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards in the databases PubMed, OVID Embase, and Cochrane Library. References were cross-examined for further articles. Data collected described the prevalence, characteristics, and management of recurrent urinary tract infections. Risk of bias assessments were performed for all studies.ResultsFrom 3342 identified articles, 597 met initial study criteria. Fifteen studies from 10 countries were included after full-text reviews. Four studies found higher recurrent urinary tract infection rates in diabetics versus non-diabetics meanwhile others reported recurrence rates from 23.4% to 37%. Four of five studies found diabetes to be a risk factor for recurrent urinary tract infection. E. coli was the most frequent causative pathogen. Antibiotic prescription results varied; however, multiple studies determined that longer treatment (≥ 5 days) did not correlate with lower recurrence rates. Risk of bias assessments found the most frequent study weakness to be identification of confounding variables.ConclusionThis review covered multiple subtopics, with few comprehensive or generalizable results, suggesting a need for more research on how recurrent urinary tract infections can be better evaluated and managed in women with type 2 diabetes.

Objective:To report the outcomes of the anterior vaginal wall suspension (AVWS) procedure for stress urinary incontinence (SUI).Materials and Methods:Following institutional review board approval, a long-term pelvic organ prolapse database of non-neurogenic patients who underwent AVWS for bothersome SUI and ≤ stage 2 anterior vaginal compartment laxity was reviewed. Any patient with prior SUI surgery or < a 6-month follow-up were excluded. Preoperative evaluation included detailed history, validated questionnaires [Urogenital Distress Inventory-Short form, visual analog quality of life score (QoL)], physical examination, and standing lateral voiding cystourethrogram (VCUG). Follow-up included VCUG at 6-12 months postoperatively, yearly examinations, and questionnaires. Failure was measured by a Kaplan-Meier curve using time to reoperation for SUI.Results:Between 1996 and 2016, 171 patients met the study criteria. The median follow-up was 4.2 years, with 26 (15%) patients having over a 10-year follow-up. Median (interquartile range): age 64 (53-70), body mass index 26 (22-30), and parity 2 (2-3). Ninety-one (53%) patients underwent AVWS with a concomitant procedure, hysterectomy being the most common. Aa and Ba points, questionnaire results, and QoL improved post-operatively and remained improved over time. VCUG findings also improved for urethral support and bladder base reduction. SUI reoperation occurred in 9 (5%) patients, including: fascial sling placement (3) or injectable agents (6).Conclusion:The AVWS procedure can correct SUI secondary to urethral hypermobility by restoration of the vaginal anatomic support to the bladder neck and bladder base.

Objective: Tamoxifen complicates management of conditions such as urinary tract infections (UTIs), urinary incontinence (UI), and/or pelvic organ prolapse (POP) that traditionally benefit from hormonal intake; thus, we reviewed our experience in managing these hormonally deprived women. Materials and Methods: After IRB approval, electronic medical records from women with current use or history of tamoxifen use and referred to a tertiary care center with female pelvic medicine and reconstructive surgery expertise for UTI, UI, and/or POP were reviewed. Results: From 2015 to 2020, 32 women treated with tamoxifen 10?40?mg for a median of 4 years were referred for UTIs (9), UI (10), symptomatic POP (8), or for a combination of these (5). Participants with UTI treated with antibiotics, prophylactic supplements, and/or electrofulguration had satisfactory response at median follow-up of 1 year (interquartile range [IQR]: 0.5?1). Ten of 15 women with UI chose intervention, with no self-reported UI recurrence at median follow-up of 2.5 years (IQR: 1?3). All but one participant with POP underwent vaginal or open/robotic mesh repairs, with satisfactory outcomes at median follow-up of 3 years (IQR: 2?7). Conclusions: The management of UTIs, UI, and POP in women on tamoxifen or unable to benefit from hormonal intake is challenging, but traditional interventions can be considered with satisfactory results.

BackgroundFemale urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described.ObjectiveWe sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery.Study designPreoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models.ResultsThe majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P < .001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women.ConclusionWomen undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

Abstract Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2–5 Hz) or medium (10–20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

AimsTo examine treatment options selected for recurrent stress urinary incontinence (rSUI) in follow-up after Burch, autologous fascial and synthetic midurethral sling (MUS) procedures.MethodsWe performed a secondary analysis of the SISTER and ToMUS trials of participants who underwent primary stress urinary incontinence (SUI) treatment (without prior SUI surgery or concomitant procedures). Using Kaplan-Meier analysis, retreatment-free survival rates by initial surgical procedure were compared. Mean MESA (Medical Epidemiologic and Social Aspects of Aging) stress index was also compared between those retreated for rSUI compared to those not retreated.ResultsHalf of the women in the SISTEr trial met inclusion criteria for this analysis (329/655, 174 Burch and 155 fascial sling), as did 444/597 (74%) of subjects in ToMUS (221 transobturator midurethral sling (TMUS), and 223 retropubic midurethral sling (RMUS). Types of surgical retreatment included autologous fascial sling (19), synthetic sling (1), and bulking agent (18). Five-year retreatment free survival rates (and standard errors) were 87% (3%), 96% (2%), 97% (1%), and 99% (0.7%) for Burch, autologous fascial sling, TMUS, and RMUS groups respectively (P

Genetic sequencing technologies have led to an increase in the identification and characterization of monogenic epilepsy syndromes. This increase has, in turn, generated strong interest in developing “precision therapies” based on the unique molecular genetics of a given monogenic epilepsy syndrome. These therapies include diets, vitamins, cell-signaling regulators, ion channel modulators, repurposed medications, molecular chaperones, and gene therapies. In this review, we evaluate these therapies from the perspective of their clinical validity and discuss the future of these therapies for individual syndromes.

Glycosaminoglycans (GAGs) are linear polysaccharides and are among the primary components of mucosal surfaces in mammalian systems. The GAG layer lining the mucosal surface of the urinary tract is thought to play a critical role in urinary tract homeostasis and provide a barrier against urinary tract infection (UTI). This key component of the host-microbe interface may serve as a scaffolding site or a nutrient source for the urinary microbiota or invading pathogens, but its exact role in UTI pathogenesis is unclear. Although members of the gut microbiota have been shown to degrade GAGs, the utilization and degradation of GAGs by the urinary microbiota or uropathogens had not been investigated. In this study, we developed an in vitro plate-based assay to measure GAG degradation and utilization and used this assay to screen a library of 37 urinary bacterial isolates representing both urinary microbiota and uropathogenic species. This novel assay is more rapid, inexpensive, and quantitative compared to previously developed assays, and can measure three of the major classes of human GAGs. Our findings demonstrate that this assay captures the well-characterized ability of Streptococcus agalactiae to degrade hyaluronic acid and partially degrade chondroitin sulfate. Additionally, we present the first known report of chondroitin sulfate degradation by Proteus mirabilis, an important uropathogen and a causative agent of acute, recurrent, and catheter-associated urinary tract infections (CAUTI). In contrast, we observed that uropathogenic Escherichia coli (UPEC) and members of the urinary microbiota, including lactobacilli, were unable to degrade GAGs.

Introduction We report on the management of intraoperative vaginal cuff perforation during robotic‐assisted mesh recto‐sacrocolpopexy for vaginal vault prolapse with defecatory dysfunction. Case presentation A 75‐year‐old woman with vaginal bulge and constipation was to undergo a joint robotic mesh recto‐sacrocolpopexy. Intraoperatively, mesh was secured to the left posterior vaginal wall following dissection. Prior to contralateral suture placement, the vaginal cuff split open and exposed an end‐to‐end anastomotic sizer previously inserted in the vagina. Due to subsequent mesh erosion risk, we proceeded with vaginotomy closure with running and interrupted absorbable sutures, removal of mesh, direct suture rectopexy to the promontory, and enterocele defect correction by reapproximating the right and left wings of the peritoneum flaps over the rectum with running sutures. Patient reported satisfactory outcomes after 2 years. Conclusion We reviewed our experience with vaginal cuff perforation during robotic‐assisted mesh recto‐sacrocolpopexy prompting enterocele repair and rectopexy without mesh.

Financial toxicity is increasingly recognized as a devastating outcome of cancer treatment but is poorly characterized in patients with early-onset colorectal cancer. Young patients are particularly vulnerable to financial toxicity as they are frequently underinsured and may suffer significant disruptions to professional and financial growth. We hypothesized that financial toxicity associated with colorectal cancer treatment confers long-lasting effects on patients' well-being and disproportionately impacts patients diagnosed at <50 years of age. A retrospective cross-sectional analysis of the National Health Interview Survey from years 2019 to 2021 was performed. Patients with a history of colorectal cancer were included and stratified by age at diagnosis. Randomly selected age-matched controls with no cancer history were used for comparison. The primary endpoint was financial toxicity, as assessed by a composite score formulated from 12 National Health Interview Survey items. The secondary endpoint was food security assessed by the United States Department of Agriculture's food security scale, embedded in the National Health Interview Survey. When compared to age-matched controls, patients with colorectal cancer experienced significant financial toxicity, as reflected by a composite financial toxicity score (P =.027). Within patients with colorectal cancer, female sex (adjusted odds ratio = 1.46, P =.046) and early-onset disease (adjusted odds ratio = 2.11, P =.002) were found to significantly increase the risk of financial toxicity. Patients with early-onset colorectal cancer more frequently experienced food insecurity (P =.011), delayed necessary medical care (P =.053), mental health counseling (P =.043), and filling prescriptions (P =.007) due to cost when compared to patients with average-onset colorectal cancer. Colorectal cancer is associated with significant long-term financial toxicity, which disproportionately impacts patients diagnosed at <50 years of age. Targeted interventions are warranted to reduce financial toxicity for patients with high-risk colorectal cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate the subjective and objective outcomes of Macroplastique® (MPQ) in women with stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD). Materials and Methods Following Institutional Review Board (IRB) approval, charts of non-neurogenic women with SUI secondary to ISD who underwent MPQ injection and had 6 months minimum follow-up were reviewed from a prospectively maintained database. Patients were divided into 3 groups: Naïve (Group I), Prior Anti-Incontinence Surgery (Group II), and combined Prior Bulking Agent and Anti-Incontinence Surgery (Group III). Data collected included SUI self-report, Urogenital Distress Inventory (UDI-6) Question 3, and VAS Quality of Life (QoL) Questionnaire scores at baseline and in follow-up. Three-dimensional ultrasound (3DUS) evaluated volume/configuration of MPQ. Success was defined after the last MPQ injection as a UDI-6 Question 3 score of 0 (dry) or 1, and no reoperation for SUI. Results From 2011-2017, 106 of 142 women met study criteria. At a median follow-up of 20 months (mean=26 months; range: 6-71), success rate was 41% for Group I, 40% for Group II, and 65% for Group III (p = 0.22). QoL scores were significantly improved over baseline in all groups. There was no significant difference in clinical outcome between the asymmetrical and symmetrical group on 3DUS. The completely dry rate was highest in Group III at 29%, compared to 4% for Group I and 15% for Group II (p = 0.05). Conclusion Macroplastique® improved subjective and objective outcome measures for SUI secondary to ISD as both a primary and secondary treatment option in women.

The past 25 years have seen a strong increase in the number of publications related to criticality in different areas of neuroscience. The potential of criticality to explain various brain properties, including optimal information processing, has made it an increasingly exciting area of investigation for neuroscientists. Recent reviews on this topic, sometimes termed brain criticality, make brief mention of clinical applications of these findings to several neurological disorders such as epilepsy, neurodegenerative disease, and neonatal hypoxia. Other clinicallyrelevant domains – including anesthesia, sleep medicine, developmental-behavioral pediatrics, and psychiatry – are seldom discussed in review papers of brain criticality. Thorough assessments of these application areas and their relevance for clinicians have also yet to be published. In this scoping review, studies of brain criticality involving human data of all ages are evaluated for their current and future clinical relevance. To make the results of these studies understandable to a more clinical audience, a review of the key concepts behind criticality (e.g., phase transitions, long-range temporal correlation, self-organized criticality, power laws, branching processes) precedes the discussion of human clinical studies. Open questions and forthcoming areas of investigation are also considered.

ABSTRACT Recent advances in the analysis of microbial communities colonizing the human body have identified a resident microbial community in the human urinary tract (UT). Compared to many other microbial niches, the human UT harbors a relatively low biomass. Studies have identified many genera and species that may constitute a core urinary microbiome. However, the contribution of the UT microbiome to urinary tract infection (UTI) and recurrent UTI (rUTI) pathobiology is not yet clearly understood. Evidence suggests that commensal species within the UT and urogenital tract (UGT) microbiomes, such as Lactobacillus crispatus, may act to protect against colonization with uropathogens. However, the mechanisms and fundamental biology of the urinary microbiome-host relationship are not understood. The ability to measure and characterize the urinary microbiome has been enabled through the development of next-generation sequencing and bioinformatic platforms that allow for the unbiased detection of resident microbial DNA. Translating technological advances into clinical insight will require further study of the microbial and genomic ecology of the urinary microbiome in both health and disease. Future diagnostic, prognostic, and therapeutic options for the management of UTI may soon incorporate efforts to measure, restore, and/or preserve the native, healthy ecology of the urinary microbiomes.

Objectives: To review various erroneous diagnoses assigned to symptomatic women after MUS incision, and report our outcomes after MUS excision in these women. Materials and Methods: Following IRB approval, a retrospective review of a prospectively collected MUS removal database was performed for non-neurogenic women who presented with continued LUTS despite a prior sling incision. Data reviewed by a neutral investigator not involved in patient care included demographics, presenting symptomatology, and outcomes after sub-urethral sling excision. Results: From 2006-2015, 18 patients were identified. Mean age was 55 + 12 years. Median time from initial placement to sling incision was 12 (range 1-108) months. Following sling incision, residual LUTS were treated with various therapies but without LUTS resolution. Indications for sling excision were obstruction (3), obstruction and pain (2), persistent vaginal pain/dyspareunia (9), recurrent vaginal exposure/dyspareunia (2), worsening urgency incontinence (1) and mixed urinary incontinence (1). Median time from sling incision to sling excision was 55 (range 5-146) months. Median follow-up after MUS excision was 12 months (range 6-45 months). Obstruction (5) and exposure (2) were all cured. Vaginal pain and dyspareunia improved in 8 of 11 women and UUI improved in one. Three women had persistent SUI and 1 developed recurrent SUI. Two women were treated satisfactorily with bulking agents, one with fascial sling and one with bulking agent followed by a fascial sling. Conclusions: Sling incision may not always resolve LUTS. In a subset of women, sling excision may eventually be needed, with variable outcomes.

OBJECTIVES To describe our experiences with a continuous quality improvement process for the standardization of multicenter urodynamic studies (UDSs) in a multi-institutional network. Multicenter UDSs can have considerable variations in testing procedures, training, equipment, and reviewer biases. METHODS A quality control process was developed that included protocol development, certification of modynamic testers, central review to assess compliance with protocol and quality, protocol modifications, standardization of equipment and signal configuration, development of an electronic signal repository, and the development of UDS Interpretation Guidelines. RESULTS We describe our experience and process in the development and implementation of a standardized UDS protocol in a multicenter surgical trial for stress urinary incontinence. The process included our protocol development, quality control measures, standardization processes, electronic signal repository, and the need for UDS Interpretation Guidelines. A urodynamic testing procedures protocol was implemented successfully by 20 urodynamic testers at nine continence treatment centers. The protocol provides explicit and detailed guidelines for equipment, calibration, patient position, specific annotations, lay language bladder sensation parameters, visual leak point pressure techniques, modifications for prolapse, and data recording. A UDS Interpretation Guidelines document provides specific suggestions for validity and plausibility determination, expected ranges of urodynamic variables, and reasonable agreement of measuring systems. Both documents are available to urodynamic investigators on the Urinary Incontinence Treatment Network website (http://WWW.Llitn.net/resourcesforphysicians.htm). CONCLUSIONS Multicenter UDSs require a continuous quality improvement process and the development of UDS testing procedures and interpretation guidelines. (c) 2007 Elsevier Inc.

Objective: To report our long-term pubovaginal sling (PVS) outcomes using fascia lata for stress urinary incontinence (SUI) secondary to intrinsic sphincteric deficiency (ISD). Methodology and methods: Following Institute Review Board approval, charts from women undergoing PVS with fascia lata, with at least 6 months of follow up, were reviewed. Preoperative and postoperative data collected included demographics, validated questionnaires, prior anti-incontinence procedures, associated repairs, urodynamic findings, and reoperation procedures for SUI. Success was defined as cure of SUI (no pad, UDI-6 Question 3 related to SUI at ≤ 1, and no SUI reoperation). Results: Between 1997 and 2013, 22 women met the inclusion criteria with mean age of 73 (52–88) years, mean BMI 29 (17–38) and mean parity 2.7 (1–4). Mean follow up was 96 months (8–190). Indication for fascia lata sling included obesity (13) and prior abdominal procedures (9), including abdominoplasty. Fifteen women had received one or more prior antiincontinence procedures and five a prior injectable agent. No perioperative complications were noted. Overall, 14 of 22 women met success criteria [UDI-6 Question 3 at 0 (10) and at 1 (4)]. Three women underwent a subsequent procedure for residual SUI with periurethral bulking agent and one is awaiting an artificial urinary sphincter. Conclusion: At long-term follow-up of over 8 years after fascia lata sling, women who underwent fascia lata sling had acceptable continence outcomes with minimal complications.

Objectives: To evaluate short-term outcomes of Macroplastique (MPQ) in women with stress urinary incontinence (SUI) using patient reported outcome and three-dimensional vaginal ultrasound (3DUS). Materials and methods: After obtaining institutional review board approval, a chart review of non-neurogenic women that received MPQ for intrinsic sphincter deficiency (ISD) was extracted from a prospective database. Patients were divided into three groups: naïve (Group I), prior incontinence surgery (Group II), and both prior incontinence surgery and bulking agent (Group III). Women with urethral hypermobility were excluded. Baseline evaluation included a history, physical examination to confirm SUI, and questionnaires [Urinary Distress Inventory-6 (UDI-6), 1 quality of life (QOL) global score based on visual analog scale], and in select patients urodynamic studies and/or standing voiding cystogram. Patient follow up included repeat questionnaires scores and 3DUS to objectively assess MPQ volume. Success was defined as sufficient improvement after one injection so that a subsequent reinjection/different SUI operation was not requested at the last follow-up visit. It was hypothesized that Group I would fare best. Results: Fifty-nine women met the inclusion criteria. Success rate was 83% for Group I, 70% for Group II, and 69% for Group III (p = 0.54) at 9 months mean follow up. Fifteen patients underwent a second 3DUS during follow up with a stable volume, compared to the first study (4.5 ± 1.5 vs. 4.4 ± 1.5, p = 0.70), which confirmed stable volumes over time. Among the failures (N = 15), nine patients proceeded with reinjection; four patients had fascial slings, and two patients had artificial sphincters. Conclusion: As confirmed by 3DUS, Macroplastique appears efficacious as a primary treatment and as a salvage treatment for SUI due to ISD in the short-term.

Purpose: To review the current literature on reported pulmonary, liver, and nerve adverse reactions (ARs) of long-term Nitrofurantoin (NF) suppression in older patients treated for urinary tract infections (UTIs). Materials and methods: An extensive literature search was performed on PubMed for the search terms “Nitrofurantoin,” and “Nitrofurantoin and lung, pulmonary, liver, nerve or ARs”. Relevant cited papers were also analyzed. Articles not in English, or related to children, or pregnant women were excluded. Results: In 43 articles and other texts meeting the inclusion criteria from 1968 to 2014, rates of long-term NF-related pulmonary ARs compared to total NF prescriptions differed worldwide, but remained extremely small at 0.001% (USA) and 0.001% for pulmonary and hepatic ARs (France). Among all NF ARs, rates of pulmonary ARs differed across the literature from 2% (UK), 3% (Holland), 5% (Sweden), to 7% (Australia). Nerve ARs were reported as .0007% and liver ARs as .0003% of total prescriptions Conclusions: Pulmonary, nerve, or liver ARs resulting from long-term NF prophylaxis in older patients treated for UTIs are potentially serious but extremely rare, and should not deter from the cautious use of NF in this population.

Purpose: Antibiotic-refractory recurrent urinary tract infections are challenging to manage. Prior studies have shown that, in selected patients, electrofulguration of cystitis may disrupt potential nidus of recurrent urinary tract infections. We report on long-term outcomes of electrofulguration in women with at least 5 years of follow-up. Materials and Methods: Following Institutional Review Board approval, we analyzed a cohort of nonneurogenic women with (3 symptomatic recurrent urinary tract infections/y and inflammatory lesions on cystoscopy who underwent electrofulguration, excluding those with alternate identifiable etiology for recurrent urinary tract infections or less than 5-year follow-up. Preoperative characteristics, antibiotic regimens, and annual urinary tract infections were reported. Primary outcome was clinical cure (0-1 urinary tract infection/y), improvement (>1 and <3/y) or failure ((3/y) at last follow-up. Secondary outcomes included need for antibiotics or repeat electrofulguration. A subanalysis was performed for women with >10-year follow-up. Results: From 2006 to 2012, 96 women met study criteria with median age 64. Median follow-up was 11 years (IQR: 10-13.5); 71 women had >10-year follow-up. Prior to electrofulguration, 74% used daily antibiotic suppression, 5% used postcoital prophylaxis, 14% used self-start therapy, and 7% were not on prophylaxis. At last post-electrofulguration visit, 72% of women were cured, 22% improved, and 6% failed. Antibiotic usage decreased post-electrofulguration (P < .05). Five percent were on continuous antibiotics at last follow-up as compared to 74% on continuous antibiotics pre-electrofulguration (McNemar P < .05). Nineteen percent of women underwent a repeat electrofulguration. Conclusions: In menopausal women with over 5-year follow-up after electrofulguration for antibiotic-refractory recurrent urinary tract infections, there appears to be durable clinical cure and improvement, with decreased need for long-term antibiotics. [ABSTRACT FROM AUTHOR]