Indwelling Urological Device Biofilm Composition and Characteristics in the Presence and Absence of Infection.

OBJECTIVE: To characterize microbial biofilms associated with different device types used in the urological field including ureteral stents, sacral neuromodulation (SNM) devices, penile prostheses, and artificial urinary sphincters (AUS). MATERIALS AND METHODS: Data from 4 studies, each reporting biofilm composition of a particular device type, were pooled and included for inter-device analysis. Studies recruited adults scheduled for ureteral stent, SNM, IPP, or AUS removal/revision. Device (n = 115) biofilms and controls were analyzed with multi-omics approaches, and compositions were compared across device types and clinical factors. RESULTS: Microbiota present on each device type was distinct from that of perineal, rectal, or urine flora (P <.01). Biofilm microbial counts (P <.001) and diversity (P = .024) differed by device type. Ureteral stents had greater microbial counts than other device types (P <.001). Staphylococcus, Pseudomonas, Lactobacillus, Ureaplasma were commonly detected across devices. Device biofilms harbored a greater proportion of Proteobacteria phylum, and the rectal, perineal, and urine flora harbored a greater proportion of Firmicutes. Unique microbe-metabolite interaction networks were identified in presence and absence of infection. Antibiotic-resistance genes including sul2 (sulfonamide resistance) and rpoB (rifampin resistance) were detected in biofilms across device types. Biofilm reconstitution in vitro differed by device type from which strains were isolated. CONCLUSION: Ureteral stents, sacral neuromodulation devices, penile prostheses, and artificial urinary sphincters harbored unique microbial and metabolite profiles that differed from those of skin, urine, and rectal flora. The findings of this study set the groundwork for investigation of novel strategies to reduce device-associated infection risk within and outside urology.

External Validation Demonstrates Machine Learning Models Outperform Human Experts in Prediction of Objective and Patient-Reported Overactive Bladder Treatment Outcomes.

OBJECTIVE: To predict treatment response for overactive bladder (OAB) for a specific patient remains elusive. We sought to develop accurate models using machine learning for prediction of objective and patient-reported treatment response to intravesical botulinum toxin (OBTX-A) injection. We sought to validate the models in a challenging setting using an external dataset of a markedly different patient cohort and dosing regimen. We hypothesized the model would outperform human experts and top available algorithms. METHODS: Algorithms using "operator splitting" designed for accuracy and efficiency even in small training datasets with variable completeness, were trained to predict objective response and patient-reported symptomatic improvement using the ROSETTA trial cohort and validated using the ABC trial cohort of patients who underwent OBTX-A. Areas under the curve (AUC) of algorithms were compared to the top publicly-available machine-learning classifier XGBoost, logistic regression with cross validation, and human expert predictions in the external validation set. RESULTS: In the validation set, the operator splitting neural network had AUC of 0.66 and outperformed XGBoost with DART (top available machine-learning classifier, AUC: 0.58), logistic regression (AUC 0.55), and human experts (AUC 0.47-0.53) for prediction of clinical responder status. It was similarly accurate in prediction of patient subjective improvement in symptoms following OBTX-A (AUC: 0.64), again outperforming other algorithms and human experts (AUC 0.41-0.62). CONCLUSION: The neural network outperformed human experts and other machine-learning approaches in prediction of objective and patient-reported OBTX-A outcomes for OAB in a challenging independent validation cohort. Clinical implementation could improve counseling and treatment selection.

Does the setting for intradetrusor onabotulinumtoxinA injection for management of overactive bladder matter?

Introduction: Intradetrusor onabotulinumtoxinA (Botox) injections, to treat idiopathic overactive bladder (OAB), can be performed in the office setting under local analgesia alone or in the operating room (OR) under local and/or sedation. The objective of this study was to compare the symptomatic improvement in patients with OAB who underwent treatment with intradetrusor onabotulinumtoxinA injections in an in-office versus the OR setting. Methods: We performed a multicenter retrospective cohort study of women with the diagnosis of refractory non-neurogenic OAB who elected to undergo treatment with intradetrusor onabotulinumtoxinA injections between January 2015 and December 2020. The electronic medical records were queried for all the demographic and peri-procedural data, including the report of subjective improvement post procedure. Patients were categorized as either "in-office" versus "OR" based on the setting in which they underwent their procedure. Results: Five hundred and thirty-nine patients met the inclusion criteria: 297 (55%) in the in-office group and 242 (45%) in the OR group. A total of 30 (5.6%) patients reported retention after their procedure and it was more common in the in-office group (8.1%) versus the OR group (2.5%), (P = 0.003). The rate of urinary tract infection within 6 months of the procedure was higher in the OR group (26.0% vs. 16.8%, P = 0.009). The overall subjective improvement rate was 77% (95% confidence interval: 73%-80%). Patients in the OR group had a higher reported improvement as compared to the in-office group (81.4% vs. 73.3%, P = 0.03). Conclusions: In this cohort study of patients with OAB undergoing intradetrusor onabotulinumtoxinA injections, post procedural subjective improvement was high regardless of the setting in which the procedure was performed.

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Urinalysis Exhibits Excellent Predictive Capacity for the Absence of Urinary Tract Infection.

OBJECTIVE: To assess predictive value of urinalysis for negative urine culture and absence of urinary tract infection, re-evaluate the microbial growth threshold for positive urine culture result, and describe antimicrobial resistance features. Urine culture is associated with 27% of U.S. hospitalizations, and unnecessary antibiotic prescription is a main antibiotic resistance contributor. METHODS: Urinalyses with urine culture from women ages 18-49 from 2013 to 2020 were studied. Clinically diagnosed urinary tract infection (CUTI) was defined as (1) uropathogen growth, (2) documented diagnosis of urinary tract infection, and (3) antibiotic prescription. Sensitivity, specificity, and diagnostic predictive values were used to assess urinalysis performance in predicting isolation of a uropathogen by culture and in detection of CUTI. RESULTS: Total 12,252 urinalyses were included. Forty-one percent of urinalyses were associated with positive urine culture and 1287 (10.5%) with CUTI. Negative urinalysis exhibited high predictive accuracy for negative urine culture (specificity 90.3%, PPV 87.3%) and absence of CUTI (specificity 92.2%, PPV 97.4%). Twenty-four percent of patients not meeting the CUTI definition were still prescribed antibiotics. Twenty-two percent of cultures associated with CUTI exhibited growth less than 100,000 CFU/mL. Escherichia coli was implemented as causing 70% of CUTIs, and 4.2% of these produced an extended spectrum beta-lactamase. CONCLUSION: Negative urinalysis exhibits high predictive accuracy for absence of CUTI. A reporting threshold of 10,000 CFU/mL is more clinically appropriate than a 100,000 CFU/mL cutpoint. Reflex culture based on urinalysis results could complement clinical judgement and improve laboratory and antibiotic stewardship in premenopausal women.

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe-Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe−metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

Cognitive impairment does not impact sacral neuromodulation implant rates for overactive bladder.

OBJECTIVE: To evaluate the impact of cognitive impairment (CI) diagnoses on sacral neuromodulation (SNM) outcomes in older patients. MATERIALS AND METHODS: We completed a retrospective review of all patients aged ≥55 years who underwent test-phase SNM (peripheral nerve evaluation (PNE) or stage 1) for overactive bladder (OAB) between 2014 and 2021 within a large multi-regional health system. Patient demographics, relevant comorbidities, CI diagnoses (dementia or mild CI), and SNM procedures were recorded. Logistic regression modeling was performed to evaluate the impact of CI on SNM implantation rates. RESULTS: Five-hundred and ten patients underwent SNM test phase (161 PNE, 349 Stage 1) during the study period. The mean age was 71.0(8.5) years, and most (80.6%) were female. Overall, 52(10.1%) patients had a CI diagnosis at the time of SNM, and 30 (5.8%) were diagnosed at a median of 18.5 [9.25, 39.5] months after SNM. Patients with CI diagnoses were older, with more comorbidities, and were more likely to undergo PNE. Univariable comparison found no difference in implantation rate based on pre-SNM CI (85.4% vs. 76.9%, p = 0.16). Multivariable analysis identified PNE (OR 0.43, 95% CI 0.26-0.71), age (OR 0.96, 95%CI 0.93-0.98), and prior beta-3 agonist use (OR 0.60, 95% CI 0.37-0.99) but not CI or dementia as independent negative predictors of implantation. Implanted patients had a median follow-up of 25 [12.0, 55.0] months. Explant and revision rates did not differ according to CI. CONCLUSION: Patients with OAB and CI diagnoses proceed to SNM implant at rates similar to patients without CI diagnoses. A diagnosis of CI should not necessarily exclude patients from SNM therapy for refractory OAB.

Neural networks outperform expert humans in predicting patient impressions of symptomatic improvement following overactive bladder treatment.

INTRODUCTION AND HYPOTHESIS: The objective was to accurately predict patient-centered subjective outcomes following the overactive bladder (OAB) treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM) using a neural network-based machine-learning approach. In the context of treatments designed to improve quality of life, a patient's perception of improvement should be the gold standard outcome measure. METHODS: Cutting-edge neural network-based algorithms using reproducing kernel techniques were trained to predict patient-reported improvements in urinary leakage and bladder function as assessed by Patient Global Impression of Improvement score using the ROSETTA trial datasets. Blinded expert urologists provided with the same variables also predicted outcomes. Receiver operating characteristic curves and areas under the curve were generated for algorithm and human expert predictions in an out-of-sample holdout dataset. RESULTS: Algorithms demonstrated excellent accuracy in predicting patient subjective improvement in urinary leakage (OBTX-A: AUC 0.75; SNM: 0.80). Similarly, algorithms accurately predicted patient subjective improvement in bladder function (OBTX-A: AUC 0.86; SNM: 0.96). The top-performing algorithms outcompeted human experts across outcome measures. CONCLUSIONS: Novel neural network-based machine-learning algorithms accurately predicted OBTX-A and SNM patient subjective outcomes, and generally outcompeted expert humans. Subtle aspects of the physician-patient interaction remain uncomputable, and thus the machine-learning approach may serve as an aid, rather than as an alternative, to human interaction and clinical judgment.

Third-line therapy for overactive bladder in the elderly: Nuances and considerations.

INTRODUCTION: Overactive bladder (OAB) disproportionally affects older adults in both incidence and severity. OAB pharmacotherapy is often problematic in the elderly due to polypharmacy, adverse side effect profiles and contraindications in the setting of multiple comorbidities, and concerns regarding the risk of incident dementia with anticholinergic use. The burden of OAB in older patients coupled with concerns surrounding pharmacotherapy options should motivate optimization of nonpharmacologic therapies in this population. At the same time, several aspects of aging may impact treatment efficacy and decision-making. This narrative review critically summarizes current evidence regarding third-line OAB therapy use in the elderly and discusses nuances and treatment considerations specific to the population. METHODS: We performed an extensive, nonsystematic evidence assessment of available literature via PubMed on onabotulinumtoxinA (BTX-A), sacral neuromodulation, and percutaneous tibial nerve stimulation (PTNS) for OAB, with a focus on study in elderly and frail populations. RESULTS: While limited, available studies show all three third-line therapies are efficacious in older populations and there is no data to support one option over another. BTX-A likely has a higher risk of urinary tract infection and retention in older compared to younger populations, especially in the frail elderly. PTNS incurs the lowest risk, although adherence is poor, largely due to logistical burdens. CONCLUSION: Advanced age and frailty should not preclude third-line therapy for refractory OAB, as available data support their efficacy and safety in these populations. Ultimately, treatment choices should be individualized and involve shared decision-making.

Machine learning provides an accurate prognostication model for refractory overactive bladder treatment response and is noninferior to human experts.

OBJECTIVE: The increasing wealth of clinical data may become unmanageable for a physician to assimilate into optimal decision-making without assistance. Utilizing a novel machine learning (ML) approach, we sought to develop algorithms to predict patient outcomes following the overactive bladder treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM). MATERIALS AND METHODS: ROSETTA datasets for overactive bladder patients randomized to OBTX-A or SNM were obtained. Novel ML algorithms, using reproducing kernel techniques were developed and tasked to predict outcomes including treatment response and decrease in urge urinary incontinence episodes in both the OBTX-A and SNM cohorts, in validation and test sets. Blinded expert urologists also predicted outcomes. Receiver operating characteristic curves were generated and AUCs calculated for comparison to lines of ignorance and the expert urologists' predictions. RESULTS: Trained algorithms demonstrated outstanding accuracy in predicting treatment response (OBTX-A: AUC 0.95; SNM: 0.88). Algorithms accurately predicted mean decrease in urge urinary incontinence episodes (MSE < 0.15) in OBTX-A and SNM. Algorithms were superior to human experts in response prediction for OBTX-A, and noninferior to human experts in response prediction for SNM. CONCLUSIONS: Novel ML algorithms were accurate, superior to expert urologists in predicting OBTX-A outcomes, and noninferior to expert urologists in predicting SNM outcomes. Some aspects of the physician-patient interaction are subtle and uncomputable, and thus ML may complement, but not supplant, a physician's judgment.

Surgical management of vaginal prolapse: current surgical concepts.

INTRODUCTION Pelvic organ prolapse (POP) is a condition defined by a loss of structural integrity within the vagina and often results in symptoms which greatly interfere with quality of life in women. POP is expected to increase in prevalence over the coming years, and the number of patients undergoing surgery for POP is expected to increase by up to 13%. Two categories of surgery for POP include obliterative and reconstructive surgery. Patient health status, goals, and desired outcomes must be carefully considered when selecting a surgical approach, as obliterative surgeries result in an inability to have sexual intercourse postoperatively. MATERIALS AND METHODS: This review article covers the role of traditional native tissue repairs, surgical options and techniques for vaginal and abdominal reconstruction for POP and the associated complications, and considerations for prevention and management of post-cystectomy vaginal prolapse. RESULTS: Studies comparing native and augmented anterior repairs demonstrate better anatomic outcomes in patients with mesh at the cost of more surgical complications, while different procedures for posterior repair result in similar improvements in symptoms and quality of life. In the management of apical prolapse, vaginal obliterative repair, namely colpocleisis, results in very low risk of recurrence at the cost of the impossibility of having sexual intercourse postoperatively. Reconstructive procedures preserve vaginal length along with the ability to have intercourse, but show higher failure rates over time. They can be divided into vaginal approaches which include sacrospinous ligament fixation (SSLF) and uterosacral vaginal vault suspension (USVS), and the abdominal approach which primarily includes abdominal sacrocolpopexy (ASC). There is evidence that ASC confers a distinct advantage over vaginal approaches with respect to symptom recurrence, sexual function, and quality of life. Patients who have had radical cystectomy for bladder cancer are at an increased risk of POP, and may benefit from preventative measures and prophylactic repair during surgery. Importantly, the success rates of POP surgery vary depending on whether anatomic or clinical definitions of success are used, with success rates improving when metrics such as the presence of symptoms are incorporated. CONCLUSIONS: The surgical management of POP should greatly take into account the postoperative goals of every patient, as different approaches result in different sexual and quality of life outcomes. It is important to consider clinical metrics in the evaluation of success for POP surgery as opposed to using exclusively anatomic criteria. Preoperative counseling is critical in managing expectations and increasing patient satisfaction postoperatively.

Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019.

PURPOSE: The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder (OAB). MATERIALS & METHODS: The primary source of evidence for the original version of this guideline was the systematic review and data extraction conducted as part of the Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment Number 187 titled Treatment of Overactive Bladder in Women (2009). That report was supplemented with additional searches capturing literature published through December 2011. Following initial publication, this guideline underwent amendment in 2014 and 2018. The current document reflects relevant literature published through October 2018. RESULTS: When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low). Such statements are provided as Standards, Recommendations, or Options. In instances of insufficient evidence, additional guidance information is provided as Clinical Principles and Expert Opinions. CONCLUSIONS: The evidence-based statements are provided for diagnosis and overall management of OAB, as well as for the various treatments. Diagnosis and treatment methodologies can be expected to change as the evidence base grows and as new treatment strategies become obtainable.

Posterior Vaginal Wall Prolapse: Suture-Based Repair.

Pelvic organ prolapse is common in parous women, although few report symptoms. The incidence of posterior compartment prolapse, or rectocele, is less well-reported. Posterior vaginal wall prolapse is associated with pain, constipation, and splinting. Surgery is the mainstay of therapy for symptomatic rectoceles. Though several surgical techniques have been described, no clear indications for type of repair have emerged. This article reviews the management strategies and draws conclusions about suture-based and site-specific techniques.

Fluoro-urodynamic Image Interpretation Is Not Altered by Using Dilute Intravesical Contrast.

OBJECTIVE: To determine if using one 250 mL bottle of intravesical contrast followed by sterile saline alters interpretation of fluoroscopic images during fluoro-urodynamics. MATERIALS AND METHODS: Subjects were randomized to receive 250 mL of intravesical contrast followed by sterile saline until maximal cystometric capacity vs non-dilute intravesical contrast alone during fluoro-urodynamics. Interpreters, blinded to study group, graded images on an ordinal rank scale rating confidence in image interpretation. Primary endpoint was differences in image interpretation between the two groups using visual grading characteristics curves and contrast-to-noise ratios (CNR). Secondary endpoints were obtaining anthropometric data such as body mass index and waist circumference to determine predictors of CNR in a multivariate multiple regression analysis. RESULTS: 26 subjects were randomized to receive dilute intravesical contrast and 22 non-dilute contrast; two subjects were unable to complete the study. There was no difference in baseline characteristics between the two groups. Visual grading characteristics demonstrated no difference in readability of the fluoroscopic images between groups and CNR was not statistically different between the two groups. No correlation was identified between CNR and waist circumference or body mass index. CONCLUSION: Interpretation of fluoro-urodynamic images and image quality was not altered with using of 250 mL of contrast followed by saline. Expert reviewers did not perceive a difference in their confidence to distinguish between the two groups. Fluoro-urodynamics can be reliably performed using only 250 mL of contrast without compromising the ability to read the fluoroscopic images.