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.

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.

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.

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.

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.

Medication Discontinuation Following Transurethral Prostatectomy: an Unrecognized Effectiveness Measure?

PURPOSE OF REVIEW: Freedom from medication is a common goal for patients undergoing surgical treatment of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Knowing medication discontinuation rates following various forms of transurethral prostatectomy may aid patient counseling and assessing the comparative effectiveness of different approaches. This review examined discontinuation rates of BPH/LUTS medications following transurethral prostatectomy. RECENT FINDINGS: Rates of BPH/LUTS medication use after transurethral resection of the prostate varied from 15% to 55%, and discontinuation rates were 54-95% across medications and follow-up periods. For laser prostatectomy, approximately 18% of patients continued medications postoperatively and discontinuation rates ranged from 53% to 75%. Minimal data on holmium laser enucleation existed. For reference, medication discontinuation rates after transurethral needle ablation or microwave therapy were only 15-28%. No recommendations or best practices inform the use of medical therapy following BPH surgery. Rates of BPH/LUTS medication use following transurethral prostatectomy are considerable.

Advances in Ambulatory Urodynamics.

PURPOSE OF REVIEW: This manuscript reviews recent technological advances in ambulatory urodynamics. RECENT FINDINGS: Ambulatory urodynamics is currently recommended by the International Continence Society as a second-line diagnostic tool in patients with nondiagnostic traditional urodynamics. Novel techniques involving telemetric monitoring are in development, which utilize catheter-free wireless systems to address several recognized shortcomings of inoffice urodynamic studies. Current research in catheter-free bladder pressure measurements involves either an intravesical, intradetrusor, or transdetrusor approach. Real-time bladder volume estimation may be performed using ultrasonography, near-infrared spectroscopy, or bladder volume conductance measurement. Ambulatory urodynamics can measure bladder function in the "real world" setting, capturing physiological bladder filling and emptying and allowing patients to reproduce the activities that may trigger their symptoms. Telemetric devices being developed represent further advances in this field and focus upon improving diagnostic capabilities, evaluating patient response to treatment, and facilitating closed-loop bladder control with neuroprosthetic integration.

Cost Comparison of Benign Prostatic Hyperplasia Treatment Options.

PURPOSE OF REVIEW: To provide an economic context within which to consider treatment options for benign prostatic hyperplasia (BPH). To this end, this review provides a comparison of the costs of combination medical therapy, operative treatment, and office-based therapies for BPH from a payer perspective. RECENT FINDINGS: Analysis of Medicare charges from the authors' institution, as well as local retail costs of medication, demonstrated a wide range in costs of commonly used BPH treatments. In this study, interventions for BPH reached cost equivalence with combination medical therapy within 6 months to 8 years. A myriad of options for managing men with symptomatic BPH exist. It is prudent not only to consider surgeon preference and patient-specific factors when selecting a treatment but also to understand the economic impact different BPH therapies confer.

Electrical stimulation of the pudendal nerve promotes neuroregeneration and functional recovery from stress urinary incontinence in a rat model.

The pudendal nerve can be injured during vaginal delivery of children, and slowed pudendal nerve regeneration has been correlated with development of stress urinary incontinence (SUI). Simultaneous injury to the pudendal nerve and its target muscle, the external urethral sphincter (EUS), during delivery likely leads to slowed neuroregeneration. The goal of this study was to determine if repeat electrical stimulation of the pudendal nerve improves SUI recovery and promotes neuroregeneration in a dual muscle and nerve injury rat model of SUI. Rats received electrical stimulation or sham stimulation of the pudendal nerve twice weekly for up to 2 wk after injury. A separate cohort of rats received sham injury and sham stimulation. Expression of brain-derived neurotrophic factor (BDNF) and ßII-tubulin expression in Onuf's nucleus were measured 2, 7, and 14 days after injury. Urodynamics, leak point pressure (LPP), and EUS electromyography (EMG) were recorded 14 days after injury. Electrical stimulation significantly increased expression of BDNF at all time points and ßII-tubulin 1 and 2 wk after injury. Two weeks after injury, LPP and EUS EMG during voiding and LPP testing were significantly decreased compared with sham-injured animals. Electrical stimulation significantly increased EUS activity during voiding, although LPP did not fully recover. Repeat pudendal nerve stimulation promotes neuromuscular continence mechanism recovery possibly via a neuroregenerative response through BDNF upregulation in the pudendal motoneurons in this model of SUI. Electrical stimulation of the pudendal nerve may therefore improve recovery after childbirth and ameliorate symptoms of SUI by promoting neuroregeneration after injury.

Can Lumbosacral Magnetic Resonance Imaging be Performed Safely in Patients with a Sacral Neuromodulation Device? An In Vivo Prospective Study.

PURPOSE: We sought to determine the safety of sacral neuromodulation in patients during lumbosacral 1.5 Tesla magnetic resonance imaging. MATERIALS AND METHODS: We prospectively recruited patients with a sacral neuromodulation implant who required lumbosacral 1.5 Tesla magnetic resonance imaging. Before imaging the patients completed validated urinary symptom questionnaires and a survey regarding the usual sacral neuromodulation sensation. The implantable pulse generator was interrogated, and impedances, battery life and stimulus amplitude sensory thresholds were assessed before and after magnetic resonance imaging. Devices were switched off before the patient entered the scanner. Patients were monitored during the study and magnetic resonance imaging related adverse events questionnaires were completed after imaging. Validated questionnaires were repeated 1 month after magnetic resonance imaging to assess for changes in sacral neuromodulation therapeutic efficacy. RESULTS: A total of 11 patients were enrolled in the study. Lower back pain, which was noted by 6 of the 11 patients (55%), was the most common indication for imaging. Immediately after magnetic resonance imaging only 1 patient reported mild discomfort during imaging at the site of the implantable pulse generator. This discomfort was present only during the scan and not afterward. Two patients reported warmth at the implantable pulse generator site during the scan, which was also present only during scanning. Patients did not report any other adverse events. There were no major changes in impedance or battery life after magnetic resonance imaging. Stimulus amplitude sensory thresholds and stimulation localization were unchanged. Validated questionnaires 1 month after imaging did not show worsening scores compared to scores before imaging. CONCLUSIONS: No significant adverse events occurred in patients implanted with a Medtronic InterStim™ II device who underwent a 1.5 Tesla lumbosacral magnetic resonance imaging scan. Therapeutic efficacy of sacral neuromodulation was unchanged 1 month after imaging.