Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives.

Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as "a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span". Despite the widespread prevalence of UAB/DU, there are significant gaps in our understanding of its pathophysiological mechanisms, diagnosis, and treatment compared with overactive bladder (OAB) and detrusor overactivity (DO). These gaps are such that clinicians regard UAB/DU as an incurable condition. In recent years, the understanding of UAB has increased. The definition of UAB has been clarified, and the diagnostic criteria for DU have been considered more comprehensively. Meanwhile, a number of non-invasive diagnostic methods have also been reported. Clinical trials involving novel drugs, electrical stimulation, and stem cell therapy have shown promising results. Therefore, this review summarizes recent reports on UAB and DU and highlights the latest advances in their diagnosis and treatment.

Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial.

BACKGROUND: Detrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men. METHODS: Nine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone. RESULTS: Cell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day. CONCLUSIONS: The results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity. Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021-Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398.

Prospective, Randomized, Double-blind, Placebo-controlled, Pilot Study of Extracorporeal Shock Wave Therapy for Detrusor Underactivity/Underactive Bladder.

BACKGROUND: Detrusor underactivity/underactive bladder (DU/UAB) is a disease with great unmet needs and no current approved drug treatment. Extracorporeal shock wave therapy (ESWT) has been shown to improve regeneration of tissue and increase detrusor contractility in preclinical studies of DU/UAB. OBJECTIVE: To assess ESWT as a treatment of DU/UAB. DESIGN, SETTING, AND PARTICIPANTS: Patients with DU/UAB were enrolled in this phase 2 randomized, double-blind, placebo-controlled, physician-initiated study. INTERVENTION: The patients were assigned to ESWT (N = 6, 2500 shocks, frequency of four pulses per second, and maximum total energy flow density of 0.25 mJ/mm2) once a week for 6 wk at the suprapubic bladder area or to placebo (N = 5, shock wave setting without energy transmission). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the average changes in postvoid residual urine (PVR) from baseline to 4 wk after treatment. Other endpoints included the average changes in 3-d voiding diary, global response assessment of patient satisfaction, Underactive Bladder Questionnaire (UAB-Q) score, and urodynamic evaluation. RESULTS AND LIMITATIONS: The difference in improvement in PVR was -157.8 ml (95% confidence interval [CI]: -380.1, 64.4) versus -6.6 ml (95% CI: -178.1, 164.9) and -77.5 ml (95% CI: -242.1, 87.1) versus 81.8 ml (95% CI: -137.2, 300.7) for ESWT versus placebo (p = 0.116 and 0.056) at 4 and 12 wk, respectively. The ESWT group exhibited a significant reduction in the UAB-Q score (-4.3; 95% CI: -9.1, 0.4) compared with the placebo group (-0.4; 95% CI: -1.8, 1.0) at 4 wk after treatment (p = 0.025), and the effects were decreased at 12 wk (p = 0.091). This study was limited by small sample size. CONCLUSIONS: ESWT was well tolerated with a statistically significant decrease of DU/UAB symptoms and a trend to decrease PVR versus placebo. These results indicate that ESWT may be a promising treatment for DU/UAB and multicenter studies are needed. PATIENT SUMMARY: Bladder shock wave therapy was studied in this randomized, double-blind, placebo-controlled study in patients with inadequate bladder emptying (underactive bladder). Bladder shock wave therapy was found to be well tolerated with an improvement in bladder emptying. These results indicate that bladder shock wave therapy may be a promising treatment for patients who cannot empty their bladder adequately.

Treatment outcomes of detrusor underactivity in women based on clinical and videourodynamic characteristics.

PURPOSE: Treatment of voiding dysfunction due to detrusor underactivity (DU) remains challenging. This study sought to determine the characteristics of video urodynamic study (VUDS) in female DU and outcomes after active treatment. METHODS: A total of 409 female patients with VUDS-proven DU were recruited. All patients received conservative bladder management, with others receiving active treatment, such as oral medication, transurethral incision of bladder neck (TUI-BN), surgery for prolapse, and urethral botulinum toxin A (BoNT-A) injection, according to their VUDS characteristics. Treatment outcomes were then analyzed by different VUDS characteristics. RESULTS: Satisfactory treatment outcomes were noted in 123 patients (30.0%), among whom 35 and 88 had a VE of > 90% and > 66.7%, respectively. A total of 165 patients (40.3%) had voiding efficiency (VE) of 33.3-66.7%, whereas 121 (29.6%) remained unable to void (12.5%) or had a VE of < 33.3% (17.1%). Conservative treatment had the worst outcome. Patients with normal or slightly reduced bladder sensation (49.3%) and those with a post-void residual (PVR) of < 250 mL (59.4%) displayed better satisfactory outcome after treatment; while TUI-BN and urethral BoNT-A injection promoted better treatment results. Patients with detrusor acontractility and a PVR of ≥ 500 mL still achieved high VE rates (> 66.7%) after TUI-BN. A 56.3% satisfactory outcome was achieved after TUI-BN, whereas 58.1% satisfactory outcome was noted in those with a tight external sphincter after medical treatment. CONCLUSION: Female patients with DU exhibited VE improvement after active treatment. Patients with very low detrusor contractility and absent bladder sensation generally exhibited poor treatment outcomes.

Therapeutic outcome of active management in male patients with detrusor underactivity based on clinical diagnosis and videourodynamic classification.

Detrusor underactivity (DU) could be resulted from many different etiologies. Patients with DU might have reduced bladder sensation, low detrusor contractility, and large post-void residual volume. This study analyzed therapeutic outcome of active management for male DU patients, based on clinical and urodynamic characteristics. Male DU patients aged > 18 years old were retrospectively reviewed from the videourodynamic study (VUDS) records in recent 10 years. The patients' demographics, VUDS results, treatment modalities, and treatment outcome were analyzed. The treatment outcomes were compared among patients with different DU subgroups, clinical diagnosis and treatment modalities. Patients with voiding efficiency of > 66.7% were considered having a successful treatment outcome. For comparison, 30 men with normal VUDS finding served as the control arm. Most of the DU patients had reduced bladder sensation. The reduced bladder sensation is closely associated with low detrusor contractility. After active treatment, a successful outcome was achieved in 68.4% of patients after bladder outlet surgery, 59.1% after urethral botulinum toxin A injection, and 57.6% after medical treatment, but only 18.2% after conservative treatment. A successful treatment outcome was achieved in patients with an intact detrusor contractility, either low (69.2%) or normal voiding pressure (81.8%), and in patients with a normal or increased bladder sensation (78.1%). However, patients with detrusor acontractile (41.3%) or absent bladder sensation (17.9%) had less favorable treatment outcome after any kind of urological management. This study revealed that active management can effectively improve voiding efficiency in patients with DU. The normal bladder sensation, presence of adequate detrusor contractility, and bladder outlet narrowing during VUDS provide effective treatment strategy for DU patients. Among all management, BOO surgery provides the best treatment outcome.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

Evaluation of pre-operative bladder contractility as a predictor of improved response rate to a staged trial of sacral neuromodulation in patients with detrusor underactivity.

PURPOSE: Sacral neuromodulation (SNM) is one of the few management options shown to improve outcomes in patients with detrusor underactivity (DU). This original research will investigate if preserved bladder contractility can predict a successful treatment with SNM. METHODS: This is a retrospective study of a prospectively collected database of consecutive patients with DU, who had a staged SNM trial from January 2013 to December 2018, with a minimum of 12 months follow-up. The primary outcome was the success of stage 1 SNM trial. RESULTS: In total, 69 patients with DU were followed. The median age was 67 [interquartile range (IQR) 74-55], median baseline bladder contractility index (BCI) 18 (IQR 67-0), and median post-void residual 200 mL (IQR 300-130). There were 35 patients (51%) that responded to a SNM trial. At a median follow-up of 23 months (IQR 39-12), three were removed for poor efficacy. In patients with detrusor acontractility (DAC), six responded (33%), compared to 29 patients (57%) with BCI > 0. This was statistically significant, p value 0.03. Younger age was also a predictive factor for SNM response, p value 0.02. There were no differences noted in those with gender, neurogenic history, previous pelvic surgery, diabetes, or pre-operative voiding history. CONCLUSION: Our study showed that patients with preserved bladder contractility are more likely to respond to a trial of SNM compared with those that have DAC. Younger age was also predictive of SNM response. UDS is the only method to accurately identify DAC patients. This information will help in patient selection and pre-operative counselling.

Evolution of male patients with detrusor underactivity and conservative treatment. Five-year follow-up. / Evolución de pacientes varones con detrusor hipoactivo y tratamiento conservador. Seguimiento a cinco años.

INTRODUCTION: The objective of the study was to compare the evolution of male patients with neurogenic detrusor underactivity (NDU) versus non-neurogenic DU (NNDU) and to establish risk factors to predict the need for clean intermittent catheterization (CIC) during the follow-up period. MATERIAL AND METHODS: Longitudinal, descriptive study of a cohort of patients diagnosed with DU, and 2,496 urodynamic studies (2008-2018) were reviewed. Patients with DU (ICS 2002 and/or Bladder contraction index (< 100)) without treatment were included. Patients with CIC or interventional treatment were excluded. Follow-up included flowmetry every six months. CIC was indicated in cases of high residual volume (PVR) > 200 mL or voiding efficiency (VE)<50%. The need for CIC during follow-up or the appearance of complications (urinary tract infections (UTI), bladder lithiasis) were compared. RESULTS: DU was found in 172 (6.89%) men. Neurological causes were observed in 106 (61,6%) cases. Finally, 62 patients were included with a mean follow-up of 4.9 years (+/- 2.6). Of these patients, 33 (53%) presented NDU and 29 (47%) NNDU. Six patients with NDU needed CIC versus none with NNDU (p = 0.04). Patients requiring CIC had higher PVR (p = 0.009) and lower VE (p = 0.017)), and there were also differences in terms of time until the need for CIC (log Rank: 0.009), which was 15.1 months [4-38]. In the multivariate analysis, none of the variables showed to be predictive of the need for CIC. CONCLUSIONS: The most common cause of DU is neurologic injury. Patients with NDU remain stable without requiring CIC. We have not detected any risk factors that identify patients at risk of needing CIC.

PRImary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study).

INTRODUCTION: Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. METHODS AND ANALYSIS: PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. ETHICS AND DISSEMINATION: Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN10327305.

Risk factors for febrile genito-urinary infection in the catheterized patients by with spinal cord injury-associated chronic neurogenic lower urinary tract dysfunction evaluated by urodynamic study and cystography: a retrospective study.

INTRODUCTION: To investigate the risk factors for febrile genito-urinary tract infection (GUTI) in spinal cord injury-associated neurogenic lower urinary tract dysfunction (NLUTD) patients who perform routine clean intermittent catheterization (CIC) evaluated by urodynamic study (UDS) and cystography. PATIENTS AND METHODS: Over a 3-year period, we retrospectively assessed risk factors for febrile UTI in 141 spinal cord injury patients diagnosed as NLUTD and performing routine CIC, regarding gender, UDS findings such as bladder compliance, maximum cystometric capacity, and cystography. RESULTS: A total of 41 patients had febrile GUTI in the follow-up period as along with 32 cases of pyelonephritis, 10 cases of epididymitis, and 1 case of prostatitis, including patients with multiple infectious diseases. The causative bacteria were Escherichia coli (14 cases) followed by Pseudomonas aeruginosa (n = 5), Klebsiella pneumoniae (n = 4), and Klebsiella oxytoca (n = 4). Antibiotic-resistant E. coli were seen, with 36.4% instances of extended-spectrum beta-lactamase production in whole of E. coli. Male gender (p = 0.018), ASIA Impairment Scale (AIS) C or more severe (p = 0.031), the number of CIC (p = 0.034), use of quinolones (p < 0.001) and severe bladder deformity (DG 2 or more, p = 0.004) were significantly associated with febrile GUTI occurrence. CONCLUSIONS: Our data demonstrated that male gender, severe bladder deformity (DG 2 or more), AIS C or more, the number of CIC, and use of quinolones were significantly associated with febrile GUTI occurrence in NLUTD patients employing routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile GUTI in these patients.

Detrusor underactivity in women: A current understanding.

AIMS: To examine the current understanding and management of detrusor underactivity (DUA) and underactive bladder (UAB) in women. METHODS: A review of the current literature was performed with a specific focus on new management strategies and treatment options for women with DUA and UAB. RESULTS: DUA has become an area of increased interest in recent years. Affecting up to 45% of older women undergoing urodynamic evaluation for non-neurogenic lower urinary tract symptoms, DUA is common. There are a variety of possible etiologies including neurogenic or myogenic dysfunction. As there is currently no cure for DUA and no way to restore the ability of the detrusor muscle to contract, management of DUA in women is mostly focused on effective bladder drainage by urinary catheterization. Clean intermittent catheterization is the gold standard for bladder drainage however for a variety of reasons, women with DUA often are managed with indwelling urethral catheter or suprapubic tube. Medications, sacral neuromodulation, and the inFlow urinary prosthesis are also treatment alternatives or additions to catheterization. Novel therapies using stem cells and gene therapy are also under investigation for the treatment of DUA and UAB. CONCLUSIONS: DUA is likely more prevalent than recognized and undertreated in women. It is vital that further research in treatment options beyond catheterization be developed for these patients to offer patients a variety of treatment options.

Medical evaluation and management of male and female voiding dysfunction: a review.

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction.

Long-term functional change of cryoinjury-induced detrusor underactivity and effects of extracorporeal shock wave therapy in a rat model.

PURPOSE: To investigate the long-term functional change of cryoinjury-induced detrusor underactivity (DU) and the therapeutic potential of repeated low-energy shock wave therapy (LESW). METHODS: Fifty-six female Sprague-Dawley rats were assigned into sham and cryoinjury of bladder with or without LESW (0.05 or 0.12 mJ/mm2; 200 pulses; twice a week for 2 weeks after cryoinjury). Under halothane anesthesia, an incision was made in lower abdomen, and cryoinjury was provoked by bilateral placement of a chilled aluminum rod on the bladder filled with 1 ml saline. Measurement of contractile responses to KCl and carbachol in vitro, conscious voiding, and histological and protein changes were performed on week 1, 2, and 4 after cryoinjury. RESULTS: Cryoinjury of bladder induced a significant decrease in the detrusor contraction amplitude at week 1 (55.0%) and week 2 (57.2%), but the decrease in the contractile response to KCl and carbachol was only noted at week 1. At week 1, significantly increased COX-2 and TGF-ß1 expression accompanied a decrease of VEGF and CGRP expression. At week 4, there was a partial recovery of voiding function and a significant increase in the Ki-67 staining. LESW treatment at higher energy level further amplified the Ki-67 staining and improved the recovery of contraction amplitude and the expression of TGF-ß1 and VEGF. CONCLUSIONS: Cryoinjury of detrusor induces DU/UAB with functional impairment lasting for up to 4 weeks, but the associated molecular changes are restored by 2 weeks. LESW improved bladder wall composition, and hastened functional recovery from cryoinjury.

The development of the ICIQ-UAB: A patient reported outcome measure for underactive bladder.

AIMS: To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry. METHODS: Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity. RESULTS: The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies. CONCLUSIONS: The validity and reliability of the ICIQ-UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.

Risk of prolapse and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor using clean intermittent catheterization versus Valsalva voiding.

AIMS: To assess the relative risks of pelvic organ prolapse (POP) and urinary complications in adult spina bifida patients with neurogenic acontractile detrusor voiding with Valsalva versus those using clean-intermittent catheterization (CIC). METHODS: We conducted a retrospective analysis including all spina bifida patients with neurogenic acontractile detrusor with a minimum follow-up of 12 months. Patients were then divided in two groups according to their bladder management: voiding with Valsalva versus CIC. The primary endpoint was any de novo or worsened rectal and/or pelvic organ prolapse (POP) diagnosed during follow-up. The secondary outcome was urinary complications defined as febrile urinary tract infections (UTI) and/or urolithiasis and/or renal failure. RESULTS: Fifty-five patients (50.9% were males) met the inclusion/exclusion criteria: 28 voiding with Valsalva and 27 performing CIC. At baseline, the rates of vaginal prolapse (44.4% vs 50%; P = 0.99), and rectal prolapse/intussusception (25.9% vs 21.4%; P = 0.76) were similar in both groups. After a median follow-up of 80.6 and 65.6 months, respectively (P = 0.29), the rate of de novo or worsened rectal prolapse/intussusception was higher in the Valsalva voiding group than in the CIC group (32.1% vs 3.7%; P = 0.01). De novo or worsened vaginal prolapses were also more common in the Valsalva voiding group, but it did not reach statistical significance (33.3% vs 11.1%; P = 0.29). CONCLUSIONS: Valsalva voiding might be harmful in adult spina bifida patients with neurogenic acontractile detrusor as it may increase the risk of rectal prolapse/intussusception. Overall, the prevalence of POP and rectal prolapse was high in both groups.

New technology assessment and current and upcoming therapies for underactive bladder.

BACKGROUND AND AIMS: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder. METHODS: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB. RESULTS: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria. 2) Should residual urine volume be the primary outcome parameter and how often should it be measured? 3) Are there secondary measures that should have a place in UAB trials, such as change in the number of catheterizations, quality of life measures, etc.? 4) Use and format of bladder voiding and catheterization diary for trials. 5) Define role and technique of urodynamics in UAB trials. Are urodynamics required to monitor, and possibly exclude, individuals with high pressure voiding induced by bladder prokinetic therapies? 6) Development and use of UAB questionnaires. DISCUSSION AND CONCLUSION: The UAB regulatory working group recognizes the path forward should include engaging the FDA and other regulatory organizations that may harmonize and formalize guidance for regulatory trial designs for therapeutics for UAB.

Current concepts of the acontractile bladder.

The acontractile bladder (AcB) is a urodynamic-based diagnosis wherein the bladder is unable to demonstrate any contraction during a pressure flow study. Although it is often grouped with underactive bladder, it is a unique phenomenon and should be investigated independently. The purpose of the present review was to examine the current literature on AcB regarding its pathology, diagnosis, current management guidelines, and future developments. We performed a review of the PubMed database, classifying the evidence for AcB pathology, diagnosis, treatment, and potential future treatments. Over the 67 years covered in our review period, 42 studies were identified that met our criteria. Studies were largely poor quality and mainly consisted of retrospective review or animal models. The underlying pathology of AcB is variable with both neurological and myogenic aetiologies. Treatment is largely tailored for renal preservation and reduction of infection. Although future developments may allow more functional restorative treatments, current treatments mainly focus on bladder drainage. AcB is a unique and understudied bladder phenomenon. Treatment is largely based on symptoms and presentation. While cellular therapy and neuromodulation may hold promise, further research is needed into the underlying neuro-urological pathophysiology of this disease so that we may better develop future treatments.

Low-intensity extracorporeal shockwave therapy ameliorates diabetic underactive bladder in streptozotocin-induced diabetic rats.

OBJECTIVES: To evaluate the therapeutic effect of once-weekly low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin (STZ)-induced diabetic rat model. MATERIALS AND METHODS: In all, 36 female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus control (DMC), and DM with Li-ESWT (DM Li-ESWT). The two DM groups received an intraperitoneal 60 mg/kg STZ injection to induce DM. The Li-ESWT was applied toward the pelvis of the rats starting 4 weeks after STZ administration and lasting for 4 weeks. The Li-ESWT was given once weekly, with an energy flux density of 0.02 mJ/mm2 at 3 Hz for 400 pulses. All rats underwent conscious cystometry, leak-point pressure (LPP) assessment, ex vivo organ-bath study, histology, immunofluorescence, and Western Blot analysis. RESULTS: Conscious cystometry revealed voiding dysfunction in the DMC group, whereas the DM Li-ESWT group showed significantly improved voiding function, reflected in a reduced post-void residual urine volume and increased LPP compared to the DMC group. Ex vivo organ-bath studies showed that Li-ESWT enhanced muscle contractile activity of the bladder and urethra during electrical-field stimulation and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology, reflected by a reduction in the intravesical lumen area and increased muscle proportion of the bladder wall. Western Blot analysis showed higher smooth muscle actin expression in the bladder wall in the DM Li-ESWT group compared to the DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibres in the DMC group, and recovery of neuronal integrity and innervation in the DM Li-ESWT group. CONCLUSIONS: In conclusion, Li-ESWT ameliorated UAB and urinary incontinence in the diabetic UAB rat model. The improvement appears to be the result of restoration of bladder and urethral structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.

The role of urodynamics in the surgical management of benign prostatic obstruction.

PURPOSE OF REVIEW: Benign prostatic obstruction (BPO) is a common cause of lower urinary tract symptoms (LUTS) in elderly men. However, such symptoms are often caused by primary detrusor overactivity or underactivity. Surgical management where BPO is absent or merely incidental has a lower chance of success, and exposes the patient to the potential complications of surgery. This review discusses the diagnostic challenges facing this common presentation. RECENT FINDINGS: Most evidence comes from small, historical prospective cohort studies. A Cochrane review found only two studies that met the prespecified inclusion criteria. It concluded that urodynamics changed decision-making regarding surgery for LUTS but it was not possible to determine whether this impacted upon outcome. A systematic review of several noninvasive alternatives to urodynamics could not recommend any of them over urodynamic pressure-flow study assessment. Further research is currently in progress, the 'UPSTREAM' study, which is a randomized, multicentre trial. Men are randomized to undergo investigation with clinical evaluation and uroflowmetry, or to additionally receive urodynamics. The primary aim is to determine the impact of urodynamics on the assessment pathway. SUMMARY: Assessment of BPO involves determining whether it has a contributory role in individual patients. This is a crucial factor in outcome, as surgery can give poor results if the symptoms are principally caused by detrusor dysfunction (overactivity or underactivity). Urodynamics can help determine this if undertaken to a suitable standard. Further research will identify the precise role of this test modality.