Who Progresses to Third-Line Therapies for Overactive Bladder? Trends From the AQUA Registry.

INTRODUCTION: Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS: Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS: A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and ß3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS: Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN).

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is a well-established treatment for overactive bladder (OAB). The American Urological Association (AUA) 2008 Antibiotic Best Practice Statement (BPS) recommended trimethoprim-sulfamethoxazole or fluoroquinolone for cystoscopy with manipulation. The aim of the study was to evaluate concordance with antibiotic best practices at the time of BTX-A injection and urinary tract infection (UTI) rates based on antibiotic regimen. METHODS: Men and women undergoing first-time BTX-A injection for idiopathic OAB with 100 units in 2016, within the SUFU Research Network (SURN) multi-institutional retrospective database were included. Patients on suppressive antibiotics were excluded. The primary outcome was concordance of periprocedural antibiotic use with the AUA 2008 BPS antimicrobials of choice for "cystoscopy with manipulation." As a secondary outcome we compared the incidence of UTI among women within 30 days after BTX-A administration. Each outcome was further stratified by procedure setting (office vs. operating room; OR). RESULTS: Of the cohort of 216 subjects (175 women, 41 men) undergoing BTX-A, 24 different periprocedural antibiotic regimens were utilized, and 98 (45%) underwent BTX-A injections in the OR setting while 118 (55%) underwent BTX-A injection in the office. Antibiotics were given to 86% of patients in the OR versus 77% in office, and 8.3% of subjects received BPS concordant antibiotics in the OR versus 82% in office. UTI rates did not vary significantly among the 141 subjects who received antibiotics and had 30-day follow-up (8% BPS-concordant vs. 16% BPS-discordant, CI -2.4% to 19%, p = 0.13). A sensitivity analysis of UTI rates based on procedure setting (office vs. OR) did not demonstrate any difference in UTI rates (p = 0.14). CONCLUSIONS: This retrospective multi-institutional study demonstrates that antibiotic regimens and adherence to the 2008 AUA BPS were highly variable among providers with lower rates of BPS concordant antibiotic use in the OR setting. UTI rates at 30 days following BTX-A did not vary significantly based on concordance with the BPS or procedure setting.

Analyzing Access and Costs of Oral Medications for Overactive Bladder: Uncovering Disparities.

OBJECTIVE: To report out-of-pocket costs associated with overactive bladder (OAB) medications among Medicare beneficiaries and the uninsured. METHODS: We performed a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data (Q1-2022). FDA-approved medications for OAB were identified. We calculated out-of-pocket costs for Medicare beneficiaries in each Part D prescription benefit phase, average retail price, total yearly costs and discounted prices through cash-pay discount coupons (GoodRx) or online pharmacies like Mark Cuban Cost Plus Drug Company (MCCPDC). We also report plan utilization management requirements. RESULTS: We analyzed 5721 plan formularies for 18 medications. Mirabegron was the only beta-3 agonist (B3). Only Vesicare oral solution (14.3% of plans) and Mirabegron (0.1%) required prior authorization. Many plans required step therapy for selective generic anticholinergics (ACH) (12.4%-43.3%), while the B3 rarely required step therapy (0.6%). Monthly costs varied by coverage phase and averaged $59 for ACHs in the initial coverage phase ($14 in catastrophic; $72 in coverage gap). The monthly cost for the B3 averaged $47 in the initial coverage phase ($26 in catastrophic; $129 in coverage gap). The total yearly cost for generic ACHs ranged from $494 (oxybutynin IR) to $1452 (darifenacin) and the yearly cost for brand-name ACHs ranged from $1175 (Toviaz ER) to $2198 (Oxytrol). The total yearly cost for the B3 was $1283. CONCLUSION: We evaluated coverage, out-of-pocket costs, total yearly costs, and utilization management for OAB medications to make pricing more transparent. While selective medications may be "covered," coverage does not translate into affordable drug prices.

Factors Influencing Medication Selection for Management of Overactive Bladder: Trends and Insights From AUA Quality Registry.

OBJECTIVE: To determine how a patient's demographics, including insurance type, race/ethnicity, gender, and age, may impact the choice of medication prescribed for overactive bladder (OAB). METHODS: We queried the AUA Quality Registry for adults between 2014 and 2020 with a diagnosis of OAB for >1year, excluding neurogenic causes. Variables included age, race/ethnicity, gender, insurance type, medication first prescribed, year of prescription, provider metropolitan status, and provider practice type. Primary outcome was which factors were associated with increased odds of beta-3 prescription as first medication choice. RESULTS: We found 1,453,566 patients with OAB, 641,122 (44.1%) with complete data. Of these, 112,021 (17.5%) were prescribed medication. On multivariate analysis, patients with Medicaid, Medicare, and other/self-pay insurance were less likely to receive a beta-3 vs an anticholinergic compared to private or military insurance. Compared to white patients, Asian, Black, and other races were less likely to receive a beta-3, as were patients outside of metropolitan areas. Age >50, prescriptions after 2014, and nonacademic settings were associated with increased odds of beta-3 prescription. There was no difference between genders. CONCLUSION: Many nonclinical factors, including insurance type and race, may affect which medication is first prescribed for OAB. This is useful for practicing urologists and may help lower barriers to beta-3 prescription through policy change and advocacy.

Pelvic Organ Prolapse in Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) is a hereditary tissue and collagen synthesis disorder that can predispose patients to gynecologic and obstetric complications. Female patients often suffer from bothersome pelvic floor disorders, but due to the medical complexity of EDS, special considerations are needed for the treatment of pelvic organ prolapse and associated incontinence. In this paper, we present three unique cases of pelvic organ prolapse (POP) in EDS patients and delve deeper into the multidisciplinary approach involving urogynecology, rheumatology, physiatry, gastroenterology, and anesthesiology required to appropriately manage this condition.

Treatment of overactive bladder in men: Is it really different?

INTRODUCTION: Overactive bladder (OAB) in men is a topic that is gaining increasing attention as there is a wider understanding that OAB is not a female condition. There are several treatments; however, data in male populations are lacking compared to female cohorts. The high likelihood of concomitant benign prostatic hyperplasia (BPH) and benign prostatic obstruction (BPO) adds to the complexity of the treatment algorithm. The overlap in urinary storage symptoms also makes the interpretation of the literature challenging. METHODS: Articles that evaluated men with OAB and men with OAB and BPH/BPO were evaluated and assessed. RESULTS: Behavioral interventions can offer a significant benefit to male patients with OAB. Medical therapies that have been studied in men with OAB include anticholinergics, beta-3 agonists, and phosphodiesterase-5 inhibits. These agents can be offered in addition to alpha-blockers for men with coexisting BPH/BPO. The literature on Onabotulinumtoxin-A and neuromodulation modulation in the male population is growing and shows promising results. CONCLUSION: Male OAB is complex; however, there is a growing body of literature to help guide treatments. Many treatments are available and they have shown considerable success.

Consensus Current Procedural Terminology Code Definition of Source Control for Sepsis.

INTRODUCTION: Unlike antibiotic and perfusion support, guidelines for sepsis source control lack high-quality evidence and are ungraded. Internally valid administrative data methods are needed to identify cases representing source control procedures to evaluate outcomes. METHODS: Over five modified Delphi rounds, two independent reviewers identified Current Procedural Terminology (CPT) codes pertinent to source control. In each round, codes with perfect agreement were retained or excluded, whereas disagreements were reviewed by the panelists. Manual review of 400 patient records meeting Sepsis-3 criteria (2010-2017) clinically adjudicated which encounters included source control procedures (gold standard). The performance of consensus codes was compared with the gold standard to assess sensitivity, specificity, predictive values, and likelihood ratios. RESULTS: Of 5752 CPT codes, 609 consensus codes represented source control procedures. Of 400 hospitalizations for sepsis, 39 (9.8%; 95% confidence interval [CI] 7.0%-13.1%) underwent gold standard source control procedures and 29 (7.3%; 95% CI 4.9-10.3%) consensus code-defined source control procedures. Thirty consensus codes were identified (20.0% gastrointestinal/intraabdominal, 10.0% genitourinary, 13.3% hepatopancreatobiliary, 23.3% orthopedic/cranial, 23.3% soft tissue, and 10.0% intrathoracic), which had 61.5% (95% CI 44.6%-76.6%) sensitivity, 98.6% (95% CI 96.8%-99.6%) specificity, 83.2% (95% CI 66.6%-92.4%) positive, and 95.9% (95% CI 93.9%-97.2%) negative predictive values. With pretest probability at sample prevalence, an identified consensus code had a posttest probability of 83.0% (95% CI 66.0%-92.0%), whereas consensus code absence had a probability of 4.0% (95% CI 3.0-6.0) for undergoing a source control procedure. CONCLUSIONS: Using modified Delphi methodology, we created and validated CPT codes identifying source control procedures, providing a framework for evaluation of the surgical care of patients with sepsis.

Accuracy of anemia screening by point-of-care hemoglobin testing in patients seeking abortion.

OBJECTIVE: Accurate and timely diagnosis of anemia in pregnancy is necessary for safe management of abortion care. Screening for anemia in abortion care is often accomplished using commercially-available point-of-care tests from capillary blood, but the validity of this test has not been investigated in the context of abortion care. We sought to determine the accuracy of a capillary hemoglobin (Hb) among pregnant patients seeking induced abortion. STUDY DESIGN: We conducted a retrospective study of patients seeking abortion care at the University of Illinois at Chicago. We identified 108 subjects with paired capillary Hb and venous complete blood count (CBC) hemoglobin measurements within 7 days of each other and within 14 days before abortion. Agreement analysis was performed using Passing-Bablok regression and Bland-Altman plots. RESULTS: More patients were deemed anemic by capillary than by venous Hb measurement (32% vs 19%, p = 0.030). Capillary Hb correlated with venous Hb (r = 0.85, p < 0.001). The average bias for capillary Hb was -1.1 ± 1.0 g/dL. Step-wise, multivariable linear regression identified venous Hb as the only determinant of capillary Hb, and failed to identify any other predictors of bias. The agreement analysis between capillary and venous Hb by Passing-Bablok regression demonstrated systematic and proportional differences. CONCLUSION: Results from capillary Hb may be biased toward diagnosing anemia and should be interpreted with caution. IMPLICATIONS: Misdiagnosing anemia in abortion care can have several consequences and may prevent timely medical abortion or cause delayed procedural abortion. Clinical correlation, and possibly confirmation by venous complete blood count measurement, should be considered before clinical decision-making based solely upon the capillary point-of-care assay.

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation.

Neurogenic bladder management after spinal cord injury (SCI) is very challenging. Daily urethral catheterization is most commonly used to empty the bladder, which causes frequent infections of the lower urinary tract. This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13-14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40-50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20-30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal nerves bilaterally with 10 kHz stimulation to relax the external urethral sphincter and reduce the urethral outlet resistance successfully induced highly efficient (average 80-100%), low pressure (<50 cmH2O) voiding. The PNS at 5 Hz also promoted urine storage by inhibiting reflex bladder activity and increasing bladder capacity. At the end of 14-week chronic testing, low pressure efficient voiding induced by PNS was further confirmed under anesthesia by directly measuring voiding pressure using a bladder catheter inserted through the bladder dome. This study demonstrated the efficacy and safety of the PNS in awake chronic SCI cats, suggesting that a novel neuroprosthesis can be developed for humans to restore bladder function after SCI by stimulating and/or blocking the pudendal nerves.

Comparison of 2 single incision slings on the vagina in an ovine model.

BACKGROUND: Stress urinary incontinence carries a significant healthcare burden for women worldwide. Single incision slings are minimally invasive mesh devices designed to treat stress urinary incontinence. For prolapse repair, meshes with higher porosity and lower structural stiffness have been associated with improved outcomes. OBJECTIVE: In this study, we compared the higher stiffness, lower porosity Altis sling with the lower stiffness, higher porosity Solyx sling in an ovine model. We hypothesized that SIS-B would have a negative impact on the host response. STUDY DESIGN: A total of Altis and Solyx single incision slings were implanted suburethrally into sheep according to the manufacturer's instructions on minimal tension. The mesh-urethral-vaginal complex and adjacent ungrafted vagina (no mesh control) were harvested en bloc at 3 months. Masson's trichrome and picrosirius red staining of 6 µm thin sections was performed to measure interfiber distance and tissue integration. Smooth muscle contractility to a 120 mM KCl stimulus was performed in an organ bath to measure myofiber-driven contractions. Standard biochemical assays were used to quantify glycosaminoglycan, total collagen, and elastin content, and collagen subtypes. Bending stiffness was performed in response to a uniaxial force to define susceptibility to folding/buckling. Statistical analysis was performed using Mann-Whitney, Gabriel's pairwise post hoc, Wilcoxon matched-pairs, and chi-square tests. RESULTS: The animals had similar ages (3-5 years), parity (multiparous), and weights (45-72 kg). Trichrome cross sections showed that the Altis sling buckled in a "C" or "S" shape in most samples (8 of 11), whereas buckling after Solyx sling implantation was observed in only a single sample (1 of 13; P=.004). Tissue integration, as measured by the presence of collagen or smooth muscle between the mesh fibers on trichrome 4× imaging, was increased in samples implanted with the Solyx sling compared with the Altis sling (P<.05). Total collagen content decreased significantly with both products when compared with the ungrafted vagina consistent with stress shielding. There was no difference in the 2 groups with regard to glycosaminoglycan or elastin content. The Altis sling mesh tissue complex demonstrated significantly higher amounts of both collagen types I and III than the Solyx sling-implanted tissue and the ungrafted control. Smooth muscle contractility in response to 120 mM KCl was decreased after implantation of both slings compared with the sham (P=.011 and P<.01), with no difference between mesh types (P=.099). Bending stiffness in the Altis sling was more than 4 times lower than in the Solyx, indicating an increased propensity to buckle (0.0186 vs 0.0883). CONCLUSION: The structurally stiffer Altis sling had decreased tissue integration and increased propensity to buckle after implantation. Increased collagen types I and III after the implantation of this device suggests that these changes may be associated with a fibrotic response. In contrast, the Solyx sling largely maintained a flat configuration and had improved tissue integration. The deformation of the Altis sling is not an intended effect and is likely caused by its lower bending stiffness. Both meshes induced a decrease in collagen content and smooth muscle contractility similar to previous findings for prolapse meshes and consistent with stress shielding. The long-term impact of buckling warrants further investigation.

A National Survey of Motor Vehicle Crashes Among General Surgery Residents.

OBJECTIVES: Evaluate the frequency of self-reported, post-call hazardous driving events in a national cohort of general surgery residents and determine the associations between duty hour policy violations, psychiatric well-being, and hazardous driving events. SUMMARY OF BACKGROUND DATA: MVCs are a leading cause of resident mortality. Extended work shifts and poor psychiatric well-being are risk factors for MVCs, placing general surgery residents at risk. METHODS: General surgery residents from US programs were surveyed after the 2017 American Board of Surgery In-Training Examination. Outcomes included self-reported nodding off while driving, near-miss MVCs, and MVCs. Group-adjusted cluster Chi-square and hierarchical regression models with program-level intercepts measured associations between resident- and program-level factors and outcomes. RESULTS: Among 7391 general surgery residents from 260 programs (response rate 99.3%), 34.7% reported nodding off while driving, 26.6% a near-miss MVC, and 5.0% an MVC over the preceding 6 months. More frequent 80-hour rule violations were associated with all hazardous driving events: nodding off while driving {59.8% with ≥5 months with violations vs 27.2% with 0, adjusted odds ratio (AOR) 2.86 [95% confidence interval (CI) 2.21-3.69]}, near-miss MVCs, [53.6% vs 19.2%, AOR 3.28 (95% CI 2.53-4.24)], and MVCs [14.0% vs 3.5%, AOR 2.46 (95% CI 1.65-3.67)]. Similarly, poor psychiatric well-being was associated with all 3 outcomes [eg, 8.0% with poor psychiatric well-being reported MVCs vs 2.6% without, odds ratio 2.55 (95% CI 2.00-3.24)]. CONCLUSIONS: Hazardous driving events are prevalent among general surgery residents and associated with frequent duty hour violations and poor psychiatric well-being. Greater adherence to duty hour standards and efforts to improve well-being may improve driving safety.

Pudendal Nerve Block by Low-Frequency (≤1 kHz) Biphasic Electrical Stimulation.

OBJECTIVES: To test the hypothesis that poststimulation block of nerve conduction can be achieved by low-frequency (≤1 kHz) biphasic stimulation (LFBS). MATERIALS AND METHODS: A tripolar cuff electrode was placed around the pudendal nerve in cats to deliver LFBS (1 kHz, 500 Hz, and 100 Hz). Two bipolar hook electrodes were placed central and distal to the cuff electrode to induce external urethral sphincter (EUS) contractions. A catheter was inserted into the urethra to record EUS contraction pressure. Pudendal nerve block by LFBS was confirmed by the failure of the central hook electrode stimulation to induce EUS contractions, while the distal hook electrode stimulation still induced contractions. RESULTS: Pudendal nerve conduction was completely blocked by LFBS at different frequencies (1 kHz, 500 Hz, and 100 Hz) after terminating LFBS. The post-LFBS block induced at the minimal stimulation intensity and duration was fully reversible within the same time period (10-15 min on average) for the three frequencies. However, the stimulation duration to induce block significantly (p < 0.05) increased from 23 ± 8 sec to 95 ± 14 sec when frequency increased from 100 Hz to 1 kHz. CONCLUSION: This study discovered that LFBS (≤1 kHz), like high-frequency (≥5 kHz) biphasic stimulation (HFBS), can induce poststimulation block. The result provides support for the theory that biphasic stimulation waveforms block axonal conduction by changing intracellular and extracellular ion concentrations. The post-LFBS block provides the opportunity to develop new neuromodulation devices for clinical applications where initial nerve firing is acceptable.

Dissociable Effects of Monetary, Liquid, and Social Incentives on Motivation and Cognitive Control.

Humans are social creatures and, as such, can be motivated by aspects of social life (e.g., approval from others) to guide decision-making in everyday contexts. Indeed, a common view is that people may have stronger orientation toward social goals or incentives relative to other incentive modalities, such as food or money. However, current studies have only rarely addressed how social incentives compare to other types of rewards in motivating goal-directed behavior. The current study tested this claim; across two separate experiments, the effects of liquid and social incentives were compared in terms of their subsequent impact on task performance and self-reported affect and motivation. Critically, valenced social incentives offered both ecological validity (short video clips-Experiment 1) and continuity with prior stimuli used in the social reward and motivation literature (static images-Experiment 2) when examining their effect on behavior. Across both studies, the results replicate and extend prior work, demonstrating robust effects of liquid incentives on task performance and self-reported affect and motivation, while also supporting an interpretation of weaker motivational and affective effects for social incentives. These patterns of results highlight the complex and wide-ranging effects of social incentives and call into question the effectiveness of social incentives, relative to other incentive modalities, in motivating behavior.

Superficial peroneal neuromodulation of nonobstructive urinary retention in cats.

AIMS: To determine if superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR). METHODS: In α-chloralose anesthetized cats, NOUR was induced by repetitive application (4-16 times) of 30-minute tibial nerve stimulation (TNS: 5 Hz frequency, 0.2 ms pulse width) at 4 to 6 times threshold intensity (T) for inducing toe twitches. SPNS (1 Hz, 0.2 ms) at 2 to 4 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) during a cystometrogram (CMG) or during voiding (SPNSv) by a surgically implanted cuff electrode or by skin surface electrodes to determine if the stimulation reduced NOUR induced by prolonged TNS. RESULTS: During control CMGs, efficient (86.4% ± 5.5%) voiding occurred with a postvoid residual (PVR) volume equal to 14.9% ± 6.2% of control bladder capacity. NOUR elicited by prolonged TNS significantly (P < .05) increased bladder capacity to 168.6% ± 15.5% of control, reduced voiding efficiency to 30.4% ± 4.8%, and increased PVR to 109% ± 9.2% of control. Using the implanted cuff electrode, SPNSc and SPNSv significantly (P < .05) increased voiding efficiency to 66.7% ± 7.4% and 65.0% ± 5.9%, respectively, and reduced PVR to 52.2% ± 11.4% and 64.3% ± 11.6%, respectively. SPNSc but not SPNSv significantly (P < .05) reduced bladder capacity to 133.4% ± 15% of control. Transcutaneous SPNSv but not SPNSc also significantly (P < .05) reversed the TNS-induced NOUR responses. CONCLUSIONS: This study shows that SPNS is effective in reversing NOUR induced by prolonged TNS. Transcutaneous SPNS provides the opportunity to develop a noninvasive neuromodulation therapy for NOUR to treat more patients than current sacral neuromodulation therapy.

Microbe-Derived Butyrate and Its Receptor, Free Fatty Acid Receptor 3, But Not Free Fatty Acid Receptor 2, Mitigate Neointimal Hyperplasia Susceptibility After Arterial Injury.

Background Arterial restenosis after vascular surgery is a common cause of midterm restenosis and treatment failure. Herein, we aim to investigate the role of microbe-derived butyrate, FFAR2 (free fatty acid receptor 2), and FFAR3 (free fatty acid receptor 3) in mitigating neointimal hyperplasia development in remodeling murine arteries after injury. Methods and Results C57BL/6 mice treated with oral vancomycin before unilateral femoral wire injury to deplete gut microbiota had significantly diminished serum and stool butyrate and more neointimal hyperplasia development after arterial injury, which was reversed by concomitant butyrate supplementation. Deficiency of FFAR3 but not FFAR2, both receptors for butyrate, exacerbated neointimal hyperplasia development after injury. FFAR3 deficiency was also associated with delayed recovery of the endothelial layer in vivo. FFAR3 gene expression was observed in multiple peripheral arteries, and expression was increased after arterial injury. Treatment of endothelial but not vascular smooth muscle cells with the pharmacologic FFAR3 agonist 1-methylcyclopropane carboxylate stimulated cellular migration and proliferation in scratch assays. Conclusions Our results support a protective role for butyrate and FFAR3 in the development of neointimal hyperplasia after arterial injury and delineate activation of the butyrate-FFAR3 pathway as a valuable strategy for the prevention and treatment of neointimal hyperplasia.

Underactive Bladder and Bladder Outlet Procedures in Women.

PURPOSE OF REVIEW: This review outlines current options for women suffering from both stress urinary incontinence (SUI) and underactive bladder (UAB). This is often a challenging patient population; however, many treatment options are available including behavioral, pharmacologic, and surgical. Therapies can be divided into those specifically targeting either the bladder or the bladder outlet. RECENT FINDINGS: For patients with SUI and UAB, several clinical trials have helped to formulate current guidelines. Also, a number of novel techniques and therapeutic agents are currently under investigation. Current surgical treatments frequently employed for SUI include midurethral slings and urethral bulking agents. In contrast, the current treatments for UAB are limited to either sacral neuromodulation in women with Fowlers syndrome or in the majority, clean intermittent catheterization. Recent studies have investigated the use of adjustable urethral slings and novel modes of neuromodulation with varying degrees of success. SUMMARY: Choosing the best treatment plan for SUI combined with UAB involves a thorough understanding of a patient's preferences and goals. Fortunately, women have many options that can significantly benefit their quality of life.

Response of hypogastric afferent fibers to bladder distention or irritation in cats.

The goal of this study in anesthetized cats was to identify silent hypogastric nerve (HGN) afferent fibers that do not respond to bladder distention but become responsive after chemical irritation of the bladder. The HGN was split into multiple filaments small enough for recording action potentials from single or multiple afferent fibers. The bladder was distended by infusion of either saline or 0.5% acetic acid (AA) through a urethral catheter while recording intravesical pressure. A total of 90 HGN filaments from 17 cats responded to bladder distention with saline or AA. Three types of HGN afferents were identified. The first type was non-nociceptive mechano-sensitive that responded to bladder distention at normal physiological pressures (10-40 cmH2O). The second type was nociceptive mechano-sensitive that only responded to high-pressure (50-80 cmH2O) bladder distention with saline but responded to low-pressure bladder distention after sensitization with AA. The third type was chemo-sensitive nociceptive that was silent even during high-pressure bladder distention but after sensitization with AA did respond to low-pressure bladder distention. These results indicate that HGN afferents as well as pelvic nerve afferents may play a role in bladder nociception. The HGN afferent fibers that are silent during bladder distention at normal physiological pressures but become responsive after chemical irritation are important for understanding the possible pathophysiological mechanism underlying bladder allodynia in painful bladder syndrome.

Additive Inhibition of Reflex Bladder Activity Induced by Bilateral Pudendal Neuromodulation in Cats.

OBJECTIVE: To determine the inhibitory effect on bladder activity induced by bilateral pudendal neuromodulation. METHODS: In 10 cats under anesthesia, two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves for stimulation. A double lumen catheter was inserted into the bladder through the urethra to infuse saline and measure bladder pressure. During repeated cystometrograms (CMGs) pudendal nerve stimulation (PNS: 5 Hz, 0.2 ms, 5-15 min) was applied unilaterally or bilaterally at 1- or 2-times intensity threshold (T) for inducing anal sphincter twitching. PNS inhibition was indicated by the increase in bladder capacity measured by CMGs. RESULTS: Unilateral PNS at 1T did not significantly increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 30%. Bilateral PNS at 1T also failed to increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 60%, indicating an additive effect induced by the bilateral 2T PNS. Unilateral 1T PNS did not enhance the inhibitory effect induced by contra-lateral 2T PNS. CONCLUSION: This study in anesthetized cats reveals that an additive inhibition of reflex bladder activity can be induced by bilateral pudendal neuromodulation, indicating that bilateral PNS might achieve better therapeutic efficacy in treating overactive bladder (OAB) than unilateral PNS.

Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.

Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.