Associations Between Sodium-Glucose Co-transporter 2 Inhibitors and Urologic Diseases: Implications for Lower Urinary Tract Symptoms From a Multi-State Health System Analysis.

OBJECTIVE: To analyze the frequency of new urologic visits and urologic diagnoses in patients prescribed sodium-glucose co-transporter-2 inhibitors (SGLT-2is). MATERIAL AND METHODS: Records from a multi-state health system between 2014 and 2022 were reviewed to identify patients referred for outpatient urology evaluation within 2 years of diabetes medication prescription. Patients were stratified by the prescription of SGLT-2is or another diabetes medication. Frequency of urology visits within 1-year, urologic diagnoses, and prescriptions to treat lower urinary tract symptoms (LUTS) were compared. Patients were stratified by whether they had achieved HbA1c goal (≥7% or <7%) following treatment as well as by sex. Multivariable logistic regression was performed to determine if SGLT-2 use independently predicted outcomes of interest. RESULTS: 163,827 patients met inclusion criteria. Use of SGLT-2is was associated with a higher frequency of early urologic referral, balanitis/balanoposthitis, overactive bladder, urinary frequency, urgency, and need for LUTS medications in males with HbA1c ≥7%. Females on SGLT-2is with HbA1c ≥7% also had higher rates of urinary incontinence. In those with HbA1c <7%, only balanitis/balanoposthitis and urinary incontinence were higher in the SGLT-2i cohorts for males and females, respectively. Multivariable analysis found SGLT-2i use as predictive of early urology referral, balanitis/balanoposthitis, urinary urgency, frequency, overactive bladder, and need for LUTS medications in males. Multivariable analysis of females demonstrated similar results. CONCLUSION: SGLT-2is may lead to worse urologic outcomes and increased utilization of urologic care relative to other diabetic medications. Future studies are necessary to identify which patients are at highest risk of adverse urologic outcomes.

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.

Medical management of benign prostatic hyperplasia.

Medical management of benign prostatic hyperplasia (BPH) has progressed gradually in recent years and remains the starting point for most symptomatic patients seeking treatment. Beyond well-known alpha-blockers and 5-alpha reductase inhibitors, there is growing evidence for the use of phosphodiesterase-5 inhibitors and beta-3 agonists in managing the condition, which may afford additional relief of "bothersome" symptoms in some patients. This review details contemporary medical management of BPH with an emphasis on the indications for certain classes of pharmacotherapy and their relative benefits and side effects. Surgical and procedural treatment of BPH is covered in a separate review.

Complications of GreenLight Laser vs Transurethral Resection of the Prostate for Treatment of Lower Urinary Tract Symptoms: Meta-analysis of Randomized Trials.

OBJECTIVE: To compare perioperative outcomes and complications between GreenLight and transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. METHODS: A systematic review and random effects meta-analysis of randomized trials comparing GreenLight with TURP was completed. Primary outcomes included periprocedural milestones, 12 predefined complications, Clavien-Dindo class III-V complications, reoperations (all-cause), and a composite of reoperations and readmissions. Metaregression assessed the relationship between patient- and study-level factors with periprocedural outcomes and reoperation rates. RESULTS: The review included 13 randomized trials with 1757 patients (839 GreenLight; 918 TURP). Procedure time was 10 minutes (95% CI: 5 to 15; P < .001) longer with GreenLight, while catheterization time (mean difference=-1.3days; 95% CI: -1.7 to -0.9; P<.001) and hospital stay (mean difference=-2.1days; 95% CI: -2.5 to -1.7; P<.001) were shorter. Bleeding-related complications, including clot retention (risk ratio [RR]=0.12; 95% CI: 0.05 to 0.32; P<.001) and transfusion (RR=0.26; 95% CI: 0.12 to 0.58; P = .001), as well as sexual dysfunction (RR=0.66; 95% CI: 0.45 to 0.98; P = .04), were less frequent with GreenLight. All other complications occurred at similar frequencies between groups. The risks of reoperation (RR: 1.17; 95% CI: 0.82 to 1.66; P = .38) and reoperation or readmission (RR: 1.05; 95% CI: 0.76 to 1.44; P = .79) did not differ. CONCLUSION: GreenLight achieved shorter catheterization times and hospital stays with lower rates of sexual dysfunction and bleeding-related complications compared to TURP.

Contemporary surgical and procedural management of benign prostatic hyperplasia.

Interventions for benign prostatic hyperplasia have evolved from transurethral resection of the prostate and simple prostatectomy to a myriad of office-based and operating-room procedures. The contemporary approach involves matching the right procedure to the right patient, choosing on the basis of prostate characteristics, patient preference, and urologist expertise. This review details currently available and guideline-backed surgical and procedural treatments.

Penile prostheses harbor biofilms driven by individual variability and manufacturer even in the absence of clinical infection.

BACKGROUND: Culture-based studies have shown that penile prostheses harbor biofilms in the presence and absence of infection, but these findings have not been adequately validated using contemporary microbiome analytic techniques. AIM: The study sought to characterize microbial biofilms of indwelling penile prosthesis devices according to patient factors, device components, manufacturer, and infection status. METHODS: Upon penile prostheses surgical explantation, device biofilms were extracted, sonicated, and characterized using shotgun metagenomics and culture-based approaches. Device components were also analyzed using scanning electron microscopy. OUTCOMES: Outcomes included the presence or absence of biofilms, alpha and beta diversity, specific microbes identified and the presence of biofilm, and antibiotic resistance genes on each prosthesis component. RESULTS: The average age of participants from whom devices were explanted was 61 ± 11 years, and 9 (45%) of 20 had a diagnosis of diabetes mellitus. Seventeen devices were noninfected, and 3 were associated with clinical infection. Mean device indwelling time prior to explant was 5.1 ± 5.1 years. All analyzed components from 20 devices had detectable microbial biofilms, both in the presence and absence of infection. Scanning electron microscopy corroborated the presence of biofilms across device components. Significant differences between viruses, prokaryotes, and metabolic pathways were identified between individual patients, device manufacturers, and infection status. Mobiluncus curtisii was enriched in manufacturer A device biofilms relative to manufacturer B device biofilms. Bordetella bronchialis, Methylomicrobium alcaliphilum, Pseudoxanthomonas suwonensis, and Porphyrobacter sp. were enriched in manufacturer B devices relative to manufacturer A devices. The most abundant bacterial phyla were the Proteobacteria, Actinobacteria, and Firmicutes. Glycogenesis, the process of glycogen synthesis, was among the predominant metabolic pathways detected across device components. Beta diversity of bacteria, viruses, protozoa, and pathways did not differ among device components. CLINICAL IMPLICATIONS: All components of all penile prostheses removed from infected and noninfected patients have biofilms. The significance of biofilms on noninfected devices remains unknown and merits further investigation. STRENGTHS AND LIMITATIONS: Strengths include the multipronged approach to characterize biofilms and being the first study to include all components of penile prostheses in tandem. Limitations include the relatively few number of infected devices in the series, a relatively small subset of devices included in shotgun metagenomics analysis, and the lack of anaerobic and other expanded conditions for culture. CONCLUSION: Penile prosthesis biofilms are apparent in the presence and absence of infection, and the composition of biofilms was driven primarily by device manufacturer, individual variability, and infection, while being less impacted by device component.

Microbe-metabolite interaction networks, antibiotic resistance, and in vitro reconstitution of the penile prosthesis biofilm support a paradigm shift from infection to colonization.

To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern-rather than a single organism-is responsible for the transition from asymptomatic to infected or painful states.

Intraoperative Predictors of Sacral Neuromodulation Implantation and Treatment Response: Results From the ROSETTA Trial.

PURPOSE: We determined the utility of intraoperative data in predicting sacral neuromodulation outcomes in urgency urinary incontinence. MATERIALS AND METHODS: Intraoperative details of sacral neuromodulation stage 1 were recorded during the prospective, randomized, multicenter ROSETTA trial, including responsive electrodes, amplitudes, and response strengths (motor and sensory Likert scales). Stage 2 implant was performed for stage 1 success on 3-day diary with 24-month follow-up. An intraoperative amplitude response score for each electrode was calculated ranging from 0 (no response) to 99.5 (maximum response, 0.5 V). Predictors for stage 1 success and improvement at 24 months were identified by stepwise logistic regression confirmed with least absolute shrinkage and selection operator and stepwise linear regression. RESULTS: Intraoperative data from 161 women showed 139 (86%) had stage 1 success, which was not associated with number of electrodes generating an intraoperative motor and/or sensory response, average amplitude at responsive electrodes, or minimum amplitude-producing responses. However, relative to other electrodes, a best amplitude response score for bellows at electrode 3 was associated with stage 1 failure, a lower reduction in daily urgency urinary incontinence episodes during stage 1, and most strongly predicted stage 1 outcome in logistic modeling. At 24 months, those who had electrode 3 intraoperative sensory response had lower mean reduction in daily urgency urinary incontinence episodes than those who had no response. CONCLUSIONS: Specific parameters routinely assessed intraoperatively during stage 1 sacral neuromodulation for urgency urinary incontinence show limited utility in predicting both acute and long-term outcomes. However, lead position as it relates to the trajectory of the sacral nerve root appears to be important.

Effect of pulse width variations on sacral neuromodulation for overactive bladder symptoms: A prospective randomized crossover feasibility study.

INTRODUCTION/BACKGROUND: The pulse width (PW) parameter in sacral neuromodulation (SNM) is understudied, with no evidence-based guidance available on optimal PW for urinary indications. The aim of this prospective, randomized, single-blinded, 3 × 3 cross over design study was to estimate the effect of two PW settings (60 µs, 420 µs) compared to the industry standard (210 µs) on SNM efficacy, quality of life, and device parameters in patients who were stable and satisfied with their SNM treatment. METHODS/MATERIALS: Eligible patients were previously implanted and had urge incontinence or urgency-frequency with satisfaction on SNM at time of enrollment. Patients completed a 3-day voiding diary, validated questionnaires, and device interrogations with sensory threshold assessment at baseline and after a 4-week period on each of the three PW settings, to which they were randomized. Eighteen participants completed the study, as called for by power analysis. RESULTS: Eighteen patients were enrolled in the study. Mean age was 68 years and implant duration at the time of participation was 4.4 years. While PW variations did not produce significant differences in overall objective outcomes, device parameters, including sensory threshold amplitude and battery life differed significantly. Shortened PW necessitated higher amplitude while conserving battery life. Stimulus sensation location, quality, and intensity did not differ between PW. Standard PW was chosen by 11 patients after the study, 5 chose extended, and 2 chose shortened. Those who chose alternative PW achieved significant reductions in urinary frequency from enrollment -2.23 voids/day (p = 0.015). Upon sub-analysis, patients reporting "much better" or "very much better" on extended PW achieved significant reductions in urinary frequency and nocturia at 5.6 and 0.4, compared to 8.5 and 2.16 at baseline (p = 0.005, p = <0.001). Whereas those reporting "much better" or "very much better" on shortened PW achieved significant reductions in urinary frequency at 5.15 compared to 7.35 (p = 0.026). There were no adverse events or complications. CONCLUSIONS: Overall SNM effectiveness was unchanged with alternative PW; however, 39% of patients preferred alternative to standard PW and achieved significant improvements in urinary symptoms with such. Shorter PW can also provide savings in estimated battery life without sacrificing therapeutic efficacy.

Outcomes of Inflatable Penile Prosthesis following Radical Cystectomy: A Matched Cohort Analysis.

OBJECTIVE: To evaluate outcomes of inflatable-penile-prosthesis (IPP) implantation after radical-cystectomy compared to other etiologies of erectile dysfunction. MATERIALS AND METHODS: All IPPs within the past 20 years in a large regional health system were reviewed, and erectile dysfunction (ED) etiology was determined as radical-cystectomy, radical-prostatectomy, or organic/other ED. Cohorts were generated by 1:3 propensity score match using age, body mass index, and diabetes status. Baseline demographics and relevant comorbidities were evaluated. Clavien-Dindo complications, grade, and reoperation were assessed. Multivariable logarithmic regression was used to identify the predictors of 90-day complications following IPP implantation. Log-rank analysis was used to assess the time-to-reoperation after IPP implantation in patients with a history of cystectomy compared with noncystectomy etiologies. RESULTS: Of 2600 patients, 231 subjects were included in the study. Comparing patients undergoing IPP for cystectomy vs pooled noncystectomy indications, those who underwent radical-cystectomy had a higher overall complication rate (24% vs 9%, p = 0.02). Clavien-Dindo complication grades did not differ across groups. Reoperation was significantly more common following cystectomy (cystectomy: 21% vs noncystectomy: 7%, p = 0.01), however time to reoperation did not differ significantly by indication (cystectomy: 8 years vs noncystectomy: 10 years,p = 0.09). Among cystectomy patients, 85% of reoperations were due to mechanical failure. CONCLUSION: Compared to other erectile dysfunction etiologies, patients undergoing IPP with a history of cystectomy have an increased risk of complications within 90-days of implantation and need for surgical device revision, but no greater risk for high-grade complications. Overall IPP remains a valid treatment option after cystectomy.

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.