Current position of neuromodulation for bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Despite established effectiveness in overactive bladder and nonobstructive retention, neuromodulation's application in interstitial cystitis/bladder pain syndrome (IC/BPS) remains a topic of ongoing research. The purpose of this article is to review recent developments in neuromodulation as treatment of IC/BPS offering guidance for healthcare practitioners dealing with IC/BPS cases. RECENT FINDINGS: Recent research underlines the promising role of sacral, tibial and pudendal neuromodulation in management of IC/BPS symptoms. Studies reveal encouraging outcomes, particularly in alleviating urgency and frequency symptoms. However, while urgency and frequency symptoms tend to improve, comprehensive pain relief remains a challenge. Percutaneous tibial nerve stimulation (PTNS) and transcutaneous tibial nerve stimulation (TTNS) stand out due to their minimal invasive nature. Existing literature points to the need for larger prospective studies with extended follow-up periods to validate the efficacy and sustainability of neuromodulation. SUMMARY: Neuromodulation is a promising treatment modality for refractory IC/BPS. Due to the minimal invasive nature, they should be tried before rigorous surgery. However, the limited quantity of available data and the variability in pain relief outcomes necessitate cautious interpretation. The review emphasizes the need for further research.

A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

BACKGROUND: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. OBJECTIVE: A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. METHODS: A prospective, multicenter, single-arm, open-label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1-month post-implantation of the device, participants delivered therapy at their convenience and completed a 7-day voiding diary before visits 6- and 12-months post-treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy ( ≥ 50% improvement on average number of urgency-related incontinence episodes) and incidence of adverse events from implantation to 12-month post-activation. RESULTS: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12-months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent-to-treat analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. CONCLUSIONS: iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient-centric therapy for the treatment of UUI.

What Is in the Pipeline on Investigational Neuromodulation Techniques for Lower Urinary Tract Dysfunction: A Narrative Review.

OBJECTIVES: Overactive bladder (OAB) affects millions of patients worldwide. Its treatment is challenging but improves the patient's quality of life. Besides standard techniques for neuromodulation (sacral and pudendal neuromodulation and posterior tibial nerve stimulation), several new techniques have been investigated to treat symptoms of refractory OAB. The purpose of the present review is to outline the state of the art of new neuromodulation techniques for lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: In March 2023, a comprehensive MEDLINE, EMBASE, and Scopus search was carried out (keywords: LUTD, new technologies, neuromodulation, LUTS, OAB, painful bladder syndromes, etc). Articles were included according to inclusion (randomized controlled trials, prospective trials, large retrospective studies) and exclusion (case reports, outcomes not clearly expressed in full text, animal studies) criteria. The reference lists of the included studies also were scanned. Both adult and pediatric populations were included, in addition to both neurogenic and nonneurogenic OAB. A narrative review was then performed. RESULTS: Peroneal neuromodulation, transcutaneous electrical nerve stimulation, magnetic nerve stimulation, and parasacral transcutaneous neuromodulation are the most studied investigative techniques and were shown to yield promising results in treating OAB symptoms. Most studies showed promising results even in the complex scenarios of patients with OAB refractory to standard treatments. Comparing investigational techniques with standard of care and their respective clinical outcomes and safety profiles, and confronting their pros and cons, we reasonably believe that once such treatment modalities are further developed, they could play a role in the OAB treatment algorithm. CONCLUSIONS: Although the described neuromodulation techniques are being intensely studied, the available results are not yet sufficient for any guidelines to recommend their use.

Cost-effectiveness of urethral bulking polydimethylsiloxane-Urolastic® compared with mid-urethral sling surgery for stress urinary incontinence: A two-arm cohort study.

OBJECTIVE: To investigate the cost-effectiveness of urethral bulking polydimethylsiloxane-Urolastic® (PDMS-U) compared with mid-urethral sling (MUS) surgery for stress urinary incontinence (SUI) at 1-year follow-up. DESIGN: Prospective, two-arm cohort study with 2-year follow-up. SETTING: International multicentre. POPULATION: Women with moderate to severe SUI. MAIN OUTCOME MEASURES: Primary outcome was subjective cure (Patient Global Impression of Improvement). SECONDARY OUTCOMES: objective cure (negative cough stress test), Urogenital Distress Inventory (UDI-6), complications and re-interventions. Cost-effectiveness outcomes: total costs, quality-adjusted life year (QALY) using IIQ7-scores (Incontinence Impact Questionnaire) and EQ-5D-5L, incremental cost-effectiveness ratio (ICER) and monetary benefit (adjusted for baseline confounders). RESULTS: In all, 131 PDMS-U and 153 MUS surgery patients were treated. Subjective cure rates for MUS surgery and PDMS-U were, respectively: 101/112 (90%) versus 40/87 (46%), adjusted odds ratio (aOR; for age, body mass index [BMI], severity, type of urinary incontinence and previous SUI procedure) was 4.9. Objective cure rates for MUS surgery and PDMS-U were respectively: 98/109 (90%) versus 58/92 (63%), aOR 5.4. Average total costs for PDMS-U and MUS surgery were €3567 and €6688. ICER for MUS surgery cost €15 598 per IIQ QALY and €37 408 per EQ-5D-5L QALY. With a willingness to pay (WTP) of €25 000, MUS has a 84% chance of being cost-effective using IIQ, whereas PDMS-U has a 99% chance of being cost-effective using EQ-5D-5L. CONCLUSION: MUS surgery is more cost-effective in realising improved disease-specific quality of life (QoL), while PDMS-U is more cost-effective in realising improved generic QoL.

Physicians' perspectives on using a patient decision aid in female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: A treatment choice for female stress urinary incontinence (SUI) is preference sensitive for both patients and physicians. Multiple treatment options are available, with none being superior to any other. The decision-making process can be supported by a patient decision aid (PDA). We aimed to assess physicians' perceptions concerning the use of a PDA. METHODS: In a mixed methods study, urologists, gynecologists and general practitioners in the Netherlands were asked to fill out a web-based questionnaire. Questions were based on the Tailored Implementation for Chronic Diseases checklist using the following domains: guideline factors, individual health professional factors, professional interactions, incentives and resources, and capacity for organizational change. Participants were asked to grade statements using a five-point Likert scale and to answer open questions on facilitators of and barriers to implementation of a PDA. Outcomes of statement rating were quantitatively analyzed and thematic analysis was performed on the outcomes regarding facilitators and barriers. RESULTS: The response rate was 11%, with a total of 120 participants completing the questionnaire. Ninety-two of the physicians (77%) would use a PDA in female SUI. Evidence-based and unbiased content, the ability to support shared decision making, and patient empowerment are identified as main facilitators. Barriers are the expected prolonged time investment and the possible difficulty using the PDA in less health-literate patient populations. CONCLUSIONS: The majority of physicians would use a PDA for female SUI. We identified facilitators and barriers that can be used when developing and implementing such a PDA.

Patient-reported outcomes and health-related quality of life after urinary diversions.

PURPOSE OF REVIEW: To study the recent literature on health-related quality of life (HRQOL) in patients after radical cystectomy followed by urinary diversion. RECENT FINDINGS: General consensus regarding, which urinary diversion is superior in terms of HRQOL has not been reached. Although there is an increase in studies favoring the orthotopic neobladder, overall quality of these studies is poor. Other studies suggest that HRQOL outcomes in different types of urinary diversions is similar and that other factors, such as age, comorbidities and sex are more important instead. Patient choice, in consultation with the treating surgeon should be the determinant of which urinary diversion is performed. Furthermore, sexual function can play an important role in HRQOL. However, practice shows that counselling on the option of sexual-preserving techniques is still not implemented in routine clinical practice. Furthermore, studies regarding differences in HRQOL after urinary diversion between male and female individuals are lacking. SUMMARY: Thorough preoperative counselling on the different types of urinary diversion and options for sexual-preserving techniques decreases decision regret and increases HRQOL in patients after radical cystectomy.

The functioning and the complication rate of extreme long existing urinary diversions.

PURPOSE OF REVIEW: This review is timely and relevant because many patients live many years with urinary diversions. Knowledge about the long term outcome with respect to function and complications are important for patient counseling and for the manner to follow-up patients. This study was performed to investigate the functioning of urinary diversions constructed > 25 years earlier. RECENT FINDINGS: Most studies have a relatively shorter follow-up, mainly focussing on short term postoperative complications. Focussing on the long term, urinary tract infections (UTI) including pyelonephritis are common. Mild kidney function deterioration is described. SUMMARY: Retrospective study (2018-2019); 43 patients with regular follow-up at the Radboud University Medical Centre Nijmegen the Netherlands. Ileal conduit (n = 19) and ureterosigmoidostomy (n = 11) are the most common diversion types for reasons such as: bladder exstrophy (n = 15), urinary incontinence (n = 9) and malignancy (n = 8). This series with a median follow-up of 40 years, shows it is possible to live and cope with a urinary diversion for a very long time. Ureterosigmoidostomies give relatively good results. Ileal conduits are functioning properly with acceptable complication rates. 95% suffers from chronic UTI's. Kidney function deterioration was mild. Diversions for benign reasons have more complex complications compared to diversion constructed for malignant reasons. VIDEO ABSTRACT: http://links.lww.com/COU/A32.

3-Year Followup of a New Implantable Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome.

PURPOSE: We evaluated the 3-year safety and efficacy of the BlueWind Medical RENOVA™ iStim system for the treatment of overactive bladder syndrome. MATERIALS AND METHODS: All patients who previously underwent implantation with the RENOVA system were offered continued participation. The primary long-term study end point was to evaluate the safety profile based on incidence of serious adverse events (system and/or procedure related), which was measured by the impact and frequency of serious adverse events. The secondary end points included clinical improvement compared to baseline and quality of life improvement compared to baseline at 36 months, which was measured by 3-day voiding diary and quality of life questionnaires at certain time points. RESULTS: Of the 34 patients with overactive bladder syndrome who previously underwent implantation with the RENOVA system 20 consented to continuation in this 3-year followup study. Mean patient age was 56.1 years and 80% (16) of the study cohort was female. The overall treatment success rate was 75% at 36 months in the per protocol (16) and the intent to treat (20) analyses. In total, 73% of the patients reported improvement in health related quality of life scores above the minimal important difference of 10 points. CONCLUSIONS: This 3-year followup study using the BlueWind RENOVA iStim system for the treatment of overactive bladder syndrome symptoms confirms the long-term good safety profile with no technical failures reported. Lasting treatment efficacy is mirrored by a sustained positive impact on patient quality of life.

Long-term real-life adherence of percutaneous tibial nerve stimulation in over 400 patients.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is used as a treatment to reduce the complaints of overactive bladder (OAB). Although it is rewarding therapy patients need maintenance treatment to preserve the beneficial effect. AIM: This real-life retrospective study was performed to assess the feasibility of PTNS adherence. MATERIALS & METHODS: All patients who underwent PTNS were retrospectively included. We analyzed the following: indication, kind of treatments (pharmacologic and third-line therapy) before and after PTNS treatment, time and reason for quitting therapy. Statistical analysis was done by performing competitive-risk analysis and Kaplan-Meier curves. Patients were categorized into four groups. Group 1: all patients; group 2: all patients on maintenance PTNS therapy (continuing after 12 weeks); group 3: patients on maintenance PTNS therapy excluding the following: (a) patients with initial good response who seized treatment due to death, (b) patient who successfully switched to transcutaneous stimulation, (c) patients who were cured of their OAB symptoms, or (d) patients who relocated; and group 4: group 3 but excluding those who stopped treatment because of nonmedical reasons (physical strain, inconveniencies associated with visiting the hospital). RESULTS: Four-hundred two patients (70% female) with a median age of 70 years underwent PTNS. Underlying treatment indications were: OAB-wet (54%) and OAB-dry (29%). The median follow-up (FU) of group 1 was 4 months. Fifty-seven percent (N = 228) of the patients received maintenance PTNS therapy. Median FU in group 4 was 46 months (range, 3-111 months). Over 40% of the maintenance patients stopped PTNS because of logistic reasons and physical strain during an FU time of 6 years. CONCLUSION: The real-world data described here with is in line with earlier published work in terms of the success rate of OAB treatment. However, over 40% quit their therapy due to nonmedical reasons.

Genetic variants and expression changes in urgency urinary incontinence: A systematic review.

AIM: To perform a systematic review summarizing the knowledge of genetic variants, gene, and protein expression changes in humans and animals associated with urgency urinary incontinence (UUI) and to provide an overview of the known molecular mechanisms related to UUI. METHODS: A systematic search was performed on March 2, 2020, in PubMed, Embase, Web of Science, and the Cochrane library. Retrieved studies were screened for eligibility. The risk of bias was assessed using the ROBINS-I (human) and SYRCLE (animal) tool. Data were presented in a structured manner and in the case of greater than five studies on a homogeneous outcome, a meta-analysis was performed. RESULTS: Altogether, a total of 10,785 records were screened of which 37 studies met the inclusion criteria. Notably, 24/37 studies scored medium-high to high on risk of bias, affecting the value of the included studies. The analysis of 70 unique genes and proteins and three genome-wide association studies showed that specific signal transduction pathways and inflammation are associated with UUI. A meta-analysis on the predictive value of urinary nerve growth factor (NGF) levels showed that increased urinary NGF levels correlate with UUI. CONCLUSION: The collective evidence showed the involvement of two molecular mechanisms (signal transduction and inflammation) and NGF in UUI, enhancing our understanding of the pathophysiology of UUI. Unfortunately, the risk of bias was medium-high to high for most studies and the value of many observations remains unclear. Future studies should focus on elucidating how deficits in the two identified molecular mechanisms contribute to UUI and should avoid bias.

Midurethral support is also necessary for reflex closure of the urethra.

BACKGROUND AND OBJECTIVES: The pathophysiology of female stress urinary incontinence (SUI) is far from unraveled. Capturing all aspects of this bothersome condition in one theory remains challenging. The well-known Hammock and Integral theories, both from the early 90's, were successful in explaining a large proportion of the observations made in clinical practice. Nevertheless, some (pre)clinical observations cannot be explained by the current understanding. One of the issues concerns the pressure transmission. Is this process really a passive mechanical action, or is an additional active mechanism responsible for urethral closure? The finding that an increase in urethral pressure sometimes precedes and exceeds the increase in intravesical pressure suggests the latter. This concept has never been incorporated in one of the existing theories describing SUI. This is remarkable as a lot of evidence has been generated in recent years that proves involvement of active components. This review aims to provide an additional theory in which an active reflex closure mechanism of the urethra is incorporated. METHODS: Recent as well as older publications from clinical and animal studies are included to support the hypothesis. RESULTS: The smooth muscles of the urethra, the vascular bed, and the estrogen-influenced urethral mucosa, combined with striated muscle tone, contribute to the intra-urethral pressure. A passive transmission of force to the urethra exists only in the abdominal proximal third of the urethra. In the distal two thirds of the urethra an active closure mechanism is present, dependent on sufficient urethral support in the proper anatomical position. This active closure mechanism is generated by reflex contraction of striated muscles of the urethra and the pelvic floor. CONCLUSION: Continence is a result of passive as well as active urethral closure mechanisms. The most important factor in female continence seems to be the proper functioning of an active reflex urethral closing mechanism.

A novel leadless, miniature implantable Tibial Nerve Neuromodulation System for the management of overactive bladder complaints.

BACKGROUND: Overactive bladder is a chronic condition affecting lower urinary tract function that has a significant negative impact on QoL. OBJECTIVE: Evaluation of the BlueWind implantable tibial nerve system performance and safety in refractory OAB. DESIGN, SETTING, AND PARTICIPANTS INTERVENTION: A 6-month multi-center prospective intervention study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Objective assessment was done by voiding diary parameters including voids/day, volume voided/day, urgency assessment, leaking episodes/day, pads used/day, leak severity, and clinical success defined as a ≥50% reduction in the number of leaks/day or number of voids/day or number of episodes with degree of urgency >2 or a return to <8 voids/day on a 3 Day diary. Subjective assessment was based on OAB-q including HRQL and symptom severity score. Safety was evaluated by adverse event (AE) analysis. RESULTS AND LIMITATIONS: Thirty-four of the 36 implanted subjects completed the study. One subject withdrew voluntarily and one developed inflammation necessitating removal of the system. In the remaining subjects, 71% experienced clinical success at 6 months. Leaks/day, leak severity, and pad changes/day decreased significantly over time with 27.6% of urge incontinence subjects that became "dry." Voids/day, degree of urgency, volume/void, pads changed improved significantly. All quality of life aspects (concern, coping, sleep, and social) improved as well as symptom severity scores measured by the OAB-q. Adverse events included: implant site pain (13.9%), suspected infection (22.2%), and procedural wound complications (8.3%). CONCLUSIONS: The BlueWind implantable tibial nerve stimulator is a safe, minimally invasive system that affords OAB patients significant improvements. PATIENT SUMMARY: The performance and safety of the BlueWind RENOVA™ implantable tibial nerve neuromodulator for OAB was tested. Our preliminary results demonstrate that the system has a low risk safety profile and may be considered an effective treatment option for OAB management.

De-implementation of urodynamics in The Netherlands after the VALUE/VUSIS-2 results: a nationwide survey.

INTRODUCTION AND HYPOTHESIS: We aimed to estimate the level of de-implementation of preoperative routine urodynamics (UDS) before stress urinary incontinence (SUI) surgery in The Netherlands and to analyze facilitators and barriers. Routine UDS was performed by 37% of the medical specialists in 2010. We hypothesized that the recommendations from the recent Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) and Value of Urodynamic Evaluation (ValUE) studies would have been followed by a reduction of routine UDS. METHODS: A national survey was performed among all Dutch gynecologists and urologists dealing with SUI in daily practice. The questionnaire contained two parts: (1) respondents' characteristics and their actual care concerning preoperative UDS, and (2) facilitators and barriers. RESULTS: The response rate was 41% (127/308). Of the respondents, 93% (n = 118) did not perform routine UDS in the preoperative workup for women in this group. Professional characteristics associated with not following the recommendations were profession urologist, academic hospital, and a lower number of midurethral sling (MUS) placed yearly. Facilitators to follow the recommendation not to perform routine UDS were adequate design of the VUSIS-II study and outcome and recommendations from the studies. Barriers not to follow the recommendation were believe in the additional value of UDS, especially the pressure transmission ratio, and the presence of detrusor overactivity. CONCLUSION: According to respondents to this questionnaire, VUSIS-II and ValUE study results are well implemented in The Netherlands. The vast majority of respondents replied as not performing routine preoperative UDS in women with primary, uncomplicated (predominant) SUI. Therefore, there is no need for a further de-implementation strategy.

A New Implanted Posterior Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome: 3-Month Results of a Novel Therapy at a Single Center.

PURPOSE: This study was designed to investigate the safety and performance of a new implantable system for tibial nerve stimulation for overactive bladder symptoms. MATERIALS AND METHODS: A battery-free stimulation device for tibial nerve stimulation (BlueWind Medical, Herzliya, Israel) was implanted in 15 patients. Safety and efficacy assessments were done at 3 months after activation with a 3-day bladder diary, a 24-hour pad test and 2 quality of life questionnaires. RESULTS: Two males and 13 females were enrolled in the study. Mean age was 54 years (range 19 to 72). Five of 15 patients were previously treated with percutaneous tibial nerve stimulation and 12 experienced urgency urinary incontinence. Median operative time was 34 minutes. At 3 months of followup a significant change was seen in 24-hour frequency from a mean ± SD of 11.8 ± 3.5 to 8.1 ± 2.0 times per day (p = 0.002), the number of severe urinary urgency episodes from 6.5 ± 5.1 to 2.0 ± 2.1 times per day (p = 0.002), the number of severe incontinence episodes from 2.8 ± 5.2 to 0.3 ± 0.4 episodes per day (p = 0.017), urinary loss per day from 243 ± 388 to 39 ± 55 gm (p = 0.038) and improvement in quality of life. After implantation, 3 patients received prolonged antibiotic treatment and 3 received pain medication for 1 week. In 1 patient the device was explanted due to pain and swelling suspicious for infection, although tissue cultures did not reveal a bacterial infection. CONCLUSIONS: This novel posterior tibial nerve stimulator is safe and easy to implant with good clinical results.

Para-Urethral Injections with Urolastic® for Treatment of Female Stress Urinary Incontinence: Subjective Improvement and Safety.

INTRODUCTION: Female stress urinary incontinence (SUI) is often treated surgically. Urethral bulking agents are a minimally invasive alternative, especially in patients suffering from intrinsic sphincter deficiency, but often with limited long-term efficacy. Urolastic® is a non-deformable, non-resorbable silicone elastomer that is used as an injectable. Its properties might result in a more durable response after injection. If this durability factor can be combined with a low complication rate, this can become a useful treatment option. We therefore assessed the subjective improvement and safety after treatment with Urolastic®. MATERIALS AND METHODS: In 2 Dutch hospitals, 65 patients were treated with Urolastic®. The subjective improvement was assessed and the medical charts were reviewed for complications that appeared during the follow-up period. The complications were classified using the Clavien-Dindo classification. RESULTS: We found that 76-88% of the patients showed subjective improvement at 12-25 months follow-up. The rate of improvement experienced was 50-70%. The rate of complications classified as Clavien-Dindo >II was 24-33%. The 12 patients with 75-100% subjective improvement after 2 months, showed 85% improvement after a median of 25 months. CONCLUSIONS: With careful patient selection, Urolastic® seems to be a safe, durable and effective treatment option for female SUI.

TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in urinary bladder afferent neural pathways was investigated using spinal c-fos measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice underwent noxious bladder distention and treatment with either intravesical instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin (RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice underwent paraformaldehyde perfusion for rapid fixation and L6-S1 spinal cord sections were removed followed by immunohistochemical staining for c-fos. A number of c-fos expressing neurons in the dorsal horns of L6-S1 spinal cord transections were quantified. Groups were compared using univariate ANOVA. Even with the absence of bladder inflammation on H&E, the TRPV4 -/- mice still have a significant twofold higher c-fos expression (n = 39, SD 2) after noxious bladder distention compared to wild type mice (n = 20, SD 3). A twofold increase in c-fos expression was observed after LPS treatment in wild types (n = 42, SD 5), but no increase was seen in TRPV4 -/- mice (n = 42, SD 2). After desensitization of primary afferent C-nerve fibers with RTX, c-fos expression in TRPV4-/- mice decreased significantly (threefold) (n = 12, SD 4). Results imply that TRPV4 channels are important for bladder afferent signaling. TRPV4 -/- mice bladders generate more noxious sensory output, which is predominantly mediated through TRPV1 expressing high threshold nerve fibers. This study reveals TRPV1 related adaptive changes in afferent pathways of the TRPV4 -/- mouse. We propose that this effect is caused by a congenital impairment of low threshold nerves that mediate normal bladder filling sensations.

Neurogenic lower urinary tract dysfunction: Clinical management recommendations of the Neurologic Incontinence committee of the fifth International Consultation on Incontinence 2013.

BACKGROUND: Evidence-based guidelines for the management of neurological disease and lower urinary tract dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. AIMS: To update clinical management of neurogenic bladder dysfunction from the recommendations of the fourth ICI, 2009. MATERIALS AND METHODS: A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and consequently amended to deliver evidence-based conclusions and recommendations in 2013. RESULTS: The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic lower urinary tract dysfunction. The pathophysiology is categorized according to the nature of onset of neurological disease and the part(s) of the nervous system affected. Assessment requires clinical evaluation, general investigations, and specialized testing. Treatment primarily focuses on ensuring safety of the patient and optimizing quality of life. Symptom management covers conservative and interventional measures to aid urine storage and bladder emptying, along with containment of incontinence. A multidisciplinary approach to management is essential. DISCUSSION: The review offers a pragmatic review of management in the context of complex pathophysiology and varied evidence base. Neurourol. Urodynam. 35:657-665, 2016. © 2016 Wiley Periodicals, Inc.

Results of primary versus recurrent surgery to treat stress urinary incontinence in women.

INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in patients who had undergone primary or recurrent (secondary) surgery for stress urinary incontinence (SUI). METHODS: A retrospective cohort study that included patients who underwent surgery to treat SUI in a tertiary referral center was carried out. All patients had, predominantly, SUI. Exclusion criteria were patients with a neurogenic bladder or a neobladder and patients without postoperative follow-up (FU). The primary objective was to assess the success rate, defined as cured SUI or improved SUI at six weeks and at the latest available moment of FU. The secondary objective was to assess complications. RESULTS: A total of 541 women with SUI underwent surgery for SUI between 2002 and 2010. After exclusion of 102 patients a total of 242 patients with primary SUI and 197 patients with recurrent SUI were identified. The success rate at first FU was 89 %. At last FU (median 205 days) the success rate was 83 % (P < 0.01). There were no significant differences in success rate between primary and recurrent surgery at first FU. The overall success rate of primary surgery was 86 %; for recurrent surgery it was 79 %. During surgery, 27 bladder injuries occurred (6.2 %), with no significant difference between the two groups. At last FU, 11 patients (2.6 %) had persistent residual volume, necessitating prolonged clean intermittent self-catheterization. CONCLUSIONS: The results of recurrent surgery to treat recurrent or persistent SUI are still good in experienced hands and do not significantly differ from results of primary surgery. The complication rates are comparable to those of primary surgery.