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AIMS Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder. METHODS The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated. RESULTS Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p

BACKGROUND Among female patients with lower urinary tract symptoms, detrusor underactivity (DU), and detrusor overactivity-with-detrusor underactivity (DO-DU) are two common diagnoses. Here, we investigated the correlations between bladder wall thickness (BWT) and clinical manifestations of the two diagnoses. METHODS From 2011 to 2016, female patients with DU or DO-DU, diagnosed at our institute, were recruited. We analyzed their urodynamic parameters and collected three questionnaires (IPSS, UDI-6, OABSS). Using transabdominal sonography, the BWT was recorded. DU was defined as follows: maximum free flow rate (Qmax) ≤ 15 cc/s; detrusor pressure at maximum flow (PdetQmax) ≤ 20 cmH2O; bladder capacity > 150 cc. DO-DU was defined as follows: Qmax ≤ 15 cc/s; PdetQmax ≤ 20 cmH2O; bladder capacity ≤ 150 cc. The BWTs of the two groups were compared using the Mann-Whitney U test; the correlations among the BWTs and the results of three questionnaires were analyzed using Spearman's rank correlation coefficient. RESULTS Forty-eight female patients with DU and 13 with DO-DU were recruited. Demographic data revealed no differences between the two groups. The mean BWT of the DO-DU patients was significantly larger than that of the DU patients (4.11 vs 3.42 mm; p = 0.001). In the DO-DU group, a high correlation existed between the BWT and some of the UDI-6 items (urgency incontinence: r = 0.831, p = 0.006; incontinence related to activity: r = 0.884, p = 0.002; small amounts of leakage: r = 0.809, p = 0.008). The BWT of the DO-DU patients also exhibited a moderate correlation with the urgency incontinence from the OABSS questionnaire (r = 0.679; p = 0.044). No correlations existed between the BWT of the DU patients and any of the data from the three questionnaires. CONCLUSION The BWT in the DO-DU patients was significantly thicker than that in the DU patients. The DO-DU patients with thicker bladder walls also had higher UDI-6 scores for both urgency and urgency incontinence.

AIMS Detrusor underactivity (DU) is an understudied health concern with inadequate clinical management. The pathophysiology of DU is unclear, and current therapies fail to improve symptoms. The current studies characterized voiding function and contractility of bladder and urethral tissues in a novel rat model of DU. METHODS Female obese prone (OP) and obese resistant (OR) rats were fed a 60 kcal% fat diet at 8 weeks old. A subset of rats (n = 4/strain) underwent uroflowmetry biweekly for 18 weeks in metabolic cages. At 40-56 weeks old, rats (n = 9-10/strain) underwent instrumented cystometry under urethane anesthesia. Following cystometry, bladder and urethral tissues (n = 8-9/strain) were harvested for in vitro assessments of contractility in response to carbachol, electric field stimulation, atropine, alpha, beta-methylene ATP, and caffeine. RESULTS OP rats exhibited increased urinary frequency (p = 0.0031), decreased voided volume (p = 0.0093), and urine flow rate (p = 0.0064) compared to OR rats during uroflowmetry. Bethanechol (10 mg/kg) did not alter uroflowmetry parameters. During cystometry, OP rats exhibited decreased bladder emptying efficiency (p

Background The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms. Methods Sixteen-week-old male Sprague–Dawley rats were divided into five groups (n = 10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0 × 105 cells (250 K, 500 K, or 1000 K; K = a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses. Results CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy. Conclusions Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner. Graphical abstract

We aimed to investigate detrusor function in a previously developed rat neurogenic voiding dysfunction model that we have developed previously. We performed sham or bilateral accessory nerve injury (BACNI) surgeries on ten-week-old male Wistar/ST rats. One week after surgery, we evaluated detrusor contractility in the bladder using isometric tension and mRNA expression assays. Cholinergic contraction was attenuated in the injury model, whereas carbachol-evoked contraction was enhanced, and mRNA expression of the cholinergic receptor increased. These findings suggest that there was a reduction in neurotransmitter release causing detrusor underactivity.

Introduction and hypothesis There is still no consensus on definitions of detrusor underactivity; therefore, it is difficult to estimate the prevalence. The primary objective of the study was to evaluate the prevalence of detrusor underactivity in a cohort of patients with pelvic floor disorders according to different proposed urodynamics definitions. The secondary objectives were to estimate the association between detrusor underactivity and symptoms, anatomy and urodynamic findings and to build predictive models. Methods Patients who performed urodynamic evaluation for pelvic floor disorders between 2008 and 2016 were retrospectively analyzed. Detrusor underactivity was evaluated according to Schafer’s detrusor factor, Abrams’ bladder contractility index and Jeong cut-offs. The degree of concordance between each method was measured with Cohenʼs kappa, and differences were tested using Student’s t test, Wilcoxon test and Pearson’s chi-squared test. Results The prevalence of detrusor underactivity among a cohort of 2092 women, concerning the three urodynamic definitions, was 33.7%, 37.0% and 4.1%, respectively. Age, menopausal status, voiding/bulging symptoms, anterior and central prolapse, first desire to void and positive postvoid residual were directly related to detrusor underactivity. Conversely, stress urinary incontinence, detrusor pressures during voiding and maximum flow were inversely associated. Final models for detrusor underactivity resulted in poor accuracy for all considered definitions. Conclusions The prevalence of detrusor underactivity varies depending on the definition considered. Although several clinical variables resulted as independent predictors of detrusor underactivity, instrumental evaluation still plays a key role in the diagnosis.

Objectives To investigate if uroflowmetry (UFM) curve patterns could differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO). Methods A hundred consecutive data sets of male patients who were evaluated using UFM and invasive urodynamics (pressure flow study) were retrospectively collected. DU and BOO were diagnosed according to the bladder contractility index and BOO index. The UFM curve with two or more notches was defined as sawtooth pattern, and the interrupted pattern was defined if several curves with interruptions reducing to zero were noted. We also compared other UFM parameters including maximum and average flow rates (Qmax and Qave), voiding time, time to Qmax, the slope to first peak flow, the number of notches on the curve (sawtooth pattern), the number of curves (interrupted pattern), and the maximum drop on the sawtooth pattern. Results Twenty-five and forty-nine patients were categorized in the BOO group and the DU group, respectively. The incidence of sawtooth pattern was significantly higher in the DU group (57%) than in the BOO group (32%), while the incidence of interrupted pattern was not different between the two groups (36% in the BOO group and 49% in the DU group). There were significant differences in age (area under the curve = 0.75), prostatic volume (0.67), the slope to first peak flow (0.58), the number of notches on the curve (0.61), and the maximum drop (0.76) between the two groups. Conclusions The sawtooth UFM pattern is more common in patients with DU than in those with BOO. New parameters on UFM curve patterns could be helpful to evaluate DU and BOO without invasive urodynamics.

Objectives Both detrusor underactivity (DU) and bladder outlet obstruction are the common causes of chronic urinary retention. Some novel treatment approaches focus on modulating micturition reflex and external urethral sphincter (EUS) function. This study used electrophysiologic (EP) studies to investigate the micturition reflex and EUS conditions of chronic urinary retention patients. Methods Sixty patients with urodynamic DU and chronic urinary retention were studied using (1) bulbocavernous reflex (BCR) by electric stimulation, (2) electromyography (EMG) of the EUS, and (3) nerve conduction velocity (NCV) studies of the pudendal nerve. The EP findings were analyzed in DU patients with different etiologies. Results The BCR was positive in 41.7% of patients. In EMG studies, denervation, reinnervation, and reduced recruitment of the EUS were observed in 21.7%, 71.7%, and 88.3% patients, respectively. Decreased amplitude of pudendal nerve conduction in NCV studies was noted in 73.3% of patients. Patients with sacral neuropathy had a lower BCR positive rate (p = 0.001), a nonsignificant but higher denervation rate (p = 0.059) in EMG studies, and a higher rate of decreased amplitude in NCV (p = 0.011) than those without sacral neuropathy. Excluding patients with sacral neuropathy or diabetes mellitus, a high percentage of neurologic deficits was still detected in EP studies. Conclusions Chronic urinary retention patients with urodynamic DU not only have bladder dysfunction, but also potential neuropathy in the sacral reflexes, pudendal nerve, or urethral sphincter innervation. The neurologic deficits explored in EP studies may affect the decision-making around the therapy to restore the voiding function in DU.

OBJECTIVES To investigate and compare the effects of tadalafil and silodosin on lower urinary tract symptoms and voiding functions in men with non-neurogenic detrusor underactivity. METHODS A total of 126 treatment-naive men with lower urinary tract symptoms diagnosed as non-neurogenic detrusor underactivity received tadalafil (5 mg/day) or silodosin (8 mg/day) for 12 months. After propensity score matching, parameter changes from before administration to 12 months since treatment initiation were assessed based on subjective symptoms and urodynamic findings, including bladder contractility index and maximum urinary flow rate, and were compared between the tadalafil treatment group and the silodosin group. Detrusor underactivity was defined as bladder contractility index

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.

Purpose: To evaluate the prevalence of detrusor underactivity (DU) and bladder outlet obstruction (BOO) in women with high-grade cystocele and the impacts of cystocele repair. Methods: Between November 2010 and September 2018, women with ≥stage II cystocele were included. DU (detrusor pressure at maximum flow rate (PdetQmax)

Context: Detrusor underactivity (DUA) in women can result in urinary retention and the need for chronic bladder drainage management. Without a cure for urinary retention due to DUA, treatment options are focused on effective bladder drainage most often by intermittent or continuous catheter drainage. The inFlow intraurethral valve pump was FDA approved for use in women with this condition in 2014. Methods: Using a literature search, this clinical review sought to explore the epidemiology and commonly used treatment options for women with DUA and critically examine all available studies of the inFlow urinary prosthesis. Results: Due to a lack of effective treatments to improve detrusor function, DUA is generally considered incurable and there are limited treatment options which mostly focus on effective bladder drainage. The inFlow urinary prosthesis is a unique technology which utilizes a nonsurgically inserted urethral device for females to assist with bladder drainage due to DUA. The inFlow urinary prosthesis has been used in Europe and elsewhere for 20 years and is the subject of seven peer-reviewed clinical studies. For those that tolerate the device (about half), the inFlow urinary prosthesis has a low infection rate and side effect profile, is easy to use, and can normalize urination by returning autonomy to patients and thus improve their quality of life. Conclusion: There is no cure for women with DUA. Bladder drainage can be managed by intermittent or continuous catheterization. Appropriately selected women interested in an alternative to catheterization may be offered an on-device trial of the inFlow urinary prosthesis.

AIMS Patients with urinary retention due to detrusor acontractility (DA) might regain voiding efficiency (VE) after treatment. This study investigated the long-term outcomes and predictors of recovery following treatment. METHODS A total of 32 patients with DA were retrospectively identified and enrolled. DA was defined by Pdet .Qmax = 0 cmH2 O and postvoid residual (PVR) > 300 ml determined through videourodynamic study (VUDS). All patients received medical or surgical treatment and were followed up for at least 3 months, during which repeat VUDS was conducted. Detrusor contractility recovery was confirmed when patients were able to void with a Pdet .Qmax ≥ 10 cmH2 O after treatment. RESULTS Our patients comprised 22 women and 10 men (mean age, 73.2 ± 9.7 years; mean follow-up duration, 1.6 ± 1.8 [0.3-7.4] years). Follow-up VUDS revealed that 14 (43.9%) patients recovered from detrusor contractility, with five patients recovering within 1 year and nine after 1 year. Pdet .Qmax , voided volume, PVR, maximum flow rate, and VE significantly improved in both the recovery and nonrecovery groups. The recovery group had significantly better VE (p = .039) and significantly lower bladder compliance (74.2 ± 83.2 vs. 119 ± 82.6; p = .007) than the nonrecovery group. Receiver operating characteristic (ROC) analysis revealed an optimum bladder compliance cutoff value of

Detrusor underactivity (DU) is a common bladder dysfunction that causes lower urinary tract symptoms (LUTS) in both men and women. Currently DU can only be diagnosed by an invasive urodynamic test. Underactive bladder (UAB) is the symptom-based correlate of DU, as is the case with overactive bladder (OAB) and detrusor overactivity (DO). The International Continence Society (ICS) consensus group has recently proposed a working definition of UAB as a symptom syndrome suggestive of DU. However, a symptom complex of UAB is shared by LUTS attributable to bladder outlet obstruction (BOO). Thus, UAB is not specific for DU, leading to difficulties in determining a therapeutic target (DU or BOO) in the initial management of UAB. Under these circumstances, a consensus group was formed under the auspices of the Japanese Continence Society (JCS) and diagnostic criteria were produced to potentially identify patients likely to have DU, without a pressure/flow study-based diagnosis. Certain symptoms and several noninvasive test parameters have been reported as clinical predictors of DU, and were suggested to discriminate DU from BOO. Of these predictive factors, the more commonly used parameters were used to develop clinical diagnostic criteria for DU. This article presents the clinical diagnostic criteria for DU proposed by the JCS consensus group and aims to summarize the background discussion by the group.

Congenital penile agenesis is a rare condition with an incidence of 1 in 30 million, while other congenital malformations of the cavernous bodies are much less common. In a few cases in the literature, it has been reported that the reason for consulting a physician with these conditions is the insufficient erection. As a first reported case, we present a 16-year-old male patient with partial unilateral corpus cavernosum agenesis accompanying genitourinary anomalies. (c) 2020 Elsevier Inc.

Objectives: To evaluate the lower urinary tract symptoms, classified by the International Prostate Symptom Score (IPSS), urodynamic results (Watts Factor (WF), Bladder Contractility Index (BCI), and post void residual (PVR), in order to differentiate Detrusor Underactivity (DU) from Bladder Outlet Obstruction (BOO). Methods: Retrospective observational study performed from 2011 to 2018 at the Hospital das Clínicas of Unicamp. Two phases were done: first, to estimate sample size, and second, to evaluate the predicted parameters. Male patients with range age from 40 to 80 years were included. Patients were divided into two groups: Group 1, without BOO and with DU; Group 2, with BOO. Variables analyzed: age, comorbidities, symptoms, urodynamic data (BCI and WF) and PVR. Results: Twenty-two patients were included in each group, with medians of 68 (Group 1) and 67.5 years old (Group 2) (p = 0.8416). There was no difference for comorbidities. In relation to IPSS, medians were: 16.5 and 20.5, respectively (p = 0.858). As for symptoms, there was predominance of combination of storage and voiding symptoms in the two groups (p = 0.1810). Regarding PVR, 15 patients in Group 1 and 16 in Group 2 presented PVR> 30mL (p = 0.7411). BCI presented median values of 75 and 755.50 for Group 1 and Group 2, respectively (p

We sought to identify the symptoms and noninvasive test parameters associated with detrusor underactivity and develop a prediction model of detrusor underactivity. We analyzed clinical data on male patients with lower urinary tract symptoms who underwent pressure-flow studies.Included in analysis were 909 men who met study criteria and whose data included the International Prostate Symptom Score, free uroflowmetry, post-void residual urine volume and prostate volume. Using these data we examined the significant symptoms and noninvasive test parameters associated with detrusor underactivity and developed a prediction model of detrusor underactivity.Of the 909 patients 454 (50%) were classified with detrusor underactivity. On logistic regression analysis older patient age, smaller prostate volume, a lower urgency symptom score, a higher weak stream symptom score and a lower maximum flow rate were selected as independent predictors of detrusor underactivity. The prediction model of detrusor underactivity consisting of these 5 factors showed satisfactory performance (C statistic 0.724).We developed a prediction model of detrusor underactivity in male patients with nonneurogenic lower urinary tract symptoms. The model was based on 5 predictive factors, namely older age, smaller prostate volume, 2 symptoms (less urgency and a weak stream) and a lower maximum flow rate. The model helps estimate the probability of detrusor underactivity in clinical practice without an invasive pressure-flow study.

Aims The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. Methods Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. Results PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. Conclusions PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.

Laparoscopic discoid colorectal resection is a surgical option for bowel endometriosis, 1 of the most severe forms of endometriosis. However, no study has clearly analyzed the feasibility or the complication and recurrence rates of the procedure in a homogeneous population with specific criteria for discoid resection. The aims of this study were to evaluate the rate of conversion to segmental resection, the need for double discoid resection, and the complication and recurrence rates. We conducted a prospective study of 93 consecutive patients who underwent discoid resection in Tenon University Hospital, Paris, France. The median follow-up was 20 months. We included patients with colorectal endometriosis (≤3 cm long and90° of bowel circumference) experiencing failure of medical treatment or associated infertility. All the patients underwent a discoid colorectal resection using a transanal circular stapler. The primary end point was the rate of conversion to segmental resection (3.2%). The secondary end point was the rate of double discoid resection (6.5%). The overall complication rate was 24%, and the severe complication rate (i.e., Clavien-Dindo IIIB) was 3% (n = 4). Postoperative voiding dysfunction requiring bladder self-catheterization was observed in 16% (n = 15). The mean duration of bladder self-catherization was 30 days (range, 15-90) including 11 cases (74%) lasting less than 30 days and 4 cases lasting more than 30 days. No patients required bladder self-catheterization over 3 months. No difference in the complication rate or in voiding dysfunction was observed between double and single discoid resection. The low rate of conversion to radical resection confirms the satisfactory preoperative evaluation of bowel endometriosis. Few publications report the rate of conversion to radical surgery. This raises the crucial issue of the right indications for discoid resection. The present study confirms that discoid resection is probably the best option for small lesions because of its high feasibility and low complication rate. Further studies are required to evaluate the technique for larger colorectal endometriotic lesions.

We tried to establish a reliable detrusor underactivity (DUA) rat model and to investigate pathophysiology of chronic bladder ischemia (CBI) on voiding behavior and bladder function. Adult male rats were divided into five groups. The arterial injury (AI) groups (AI-10, AI-20, AI-30) underwent vascular endothelial damage (VED) of bilateral iliac arteries (with 10, 20, and 30 bilateral repetitions of injury, respectively) and received a 1.25% cholesterol diet. The sham group underwent sham operation and received the same diet. Controls received a regular diet. After 8 weeks, all rats underwent unanesthetized cystometrogram. Bladder tissues were processed for organ bath investigation, immunohistochemistry staining, and genome-wide gene expression analysis. Awake cystometry analysis showed that frequency of voiding contractions and micturition pressure were lower in the AI-30 group than in sham group (p

Background Underactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder. Methods Male Sprague–Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies. Results We observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue. Conclusions Ad-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB.

Age‐related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age‐related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra‐to‐bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4–7 months) and old (18–24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age‐related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age‐related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age., The prevalence of underactive bladder (UAB) symptoms increases with age; however, the underlying mechanism of age‐related bladder dysfunction is unclear. In this study on rats, we found age‐related reductions of overall urethral sensory outflow, urethral pressure development during fluid flow, and myelin present in urethral afferents, suggesting urethral neuropathy plays a role in UAB.

Aims Aging is an obvious risk factor for detrusor underactivity. We investigated the effects of aging on bladder function in spontaneously hypertensive rats. Main methods Male spontaneously hypertensive rats and Wistar Kyoto rats (used as normotensive controls) at the ages of 18, 36, 54, or 72 weeks were used. Bladder weight, blood pressure, bladder blood flow, and urodynamic and renal parameters were measured. Additionally, detrusor thickness and renal histology were evaluated. Key findings In spontaneously hypertensive rats, significant increases were observed in bladder weight/body weight ratio, blood pressure, detrusor thickness, intercontraction interval, urine output, serum creatinine, and renal glomerular and tubular scores, and decreases in bladder blood flow and urine osmolality at 72 weeks as compared to those at 18 weeks. In spontaneously hypertensive rats, significant increases were observed in single voided volume, post voiding residual urine volume, and bladder capacity, with decrease in voiding efficiency were observed at 54 or 72 weeks than at 18 weeks. However, there were no significant differences in blood pressure, urodynamic and renal parameters, detrusor thickness and renal histology among Wistar Kyoto rats of different ages. Significance In spontaneously hypertensive rats, aging induces significant increases in blood pressure, single voided volume, post voiding residual urine volume, intercontraction intervals and urine output, and decreases in voiding efficiency and bladder blood flow indicative of detrusor underactivity. Aging-related severe hypertension could induce voiding dysfunction such as detrusor underactivity via severe bladder ischemia and polyuria. Aged spontaneously hypertensive rats may be useful animal models for detrusor underactivity.

Diabetic bladder dysfunction (DBD) affects up to 50% of all patients with diabetes, characterized by symptoms of both overactive and underactive bladder. Although most diabetic bladder dysfunction studies have been performed using models with type 1 diabetes, few have been performed in models of type 2 diabetes, which accounts for ~90% of all diabetic cases. In a type 2 rat model using a high-fat diet (HFD) and two low doses of streptozotocin (STZ), we examined voiding measurements and functional experiments in urothelium-denuded bladder strips to establish a timeline of disease progression. We hypothesized that overactive bladder symptoms (compensated state) would develop and progress into symptoms characterized by underactive bladder (decompensated state). Our results indicated that this model developed the compensated state at 1 wk after STZ and the decompensated state at 4 mo after STZ administration. Diabetic bladders were hypertrophied compared with control bladders. Increased volume per void and detrusor muscle contractility to exogenous addition of carbachol and ATP confirmed the development of the compensated state. This enhanced contractility to carbachol was not due to increased levels of M3 receptor expression. Decompensation was characterized by increased volume per void, number of voids, and contractility to ATP but not carbachol. Thus, progression from the compensated to decompensated state may involve decreased contractility to muscarinic stimulation. These data suggest that the compensated state of DBD progresses temporally into the decompensated state in the male HFD/STZ model of diabetes; therefore, this male HFD/STZ model can be used to study the progression of DBD.

Objective: To analyze which factors in the history of a posterior urethral valve (PUV) patient relate to lower urinary tract symptoms (LUTS) in adulthood. This study also aimed to evaluate whether the patients have developed signs of a myogenic failure of detrusor. Materials and methods: LUTS were evaluated with a DAN-PSS questionnaire in 78 adult patients treated for PUV in childhood. Symptom scores (SS) were compared with patient characteristics and types of treatment. The results of uroflowmetry and post-voiding residual (PVR) measurements were collected from their latest visit to Helsinki University Children's Hospital. Results: The median total symptom score (TSS) was 1 (IQR = 0-5, range = 0-18). The patient age during the investigation and SS were associated (R = 0.220, p = 0.032), but the primary creatinine level and SS were not (R = 0.260, p = 0.081). The median age for achieving continence was 6.3 years. The SS and the age when becoming continent were not associated (p = 0.365 and p = 0.679, respectively). In the age group of 39 years or more, 19 patients with a previous bladder neck incision (BNI) had a higher storage-SS than 15 patients without any previous bladder neck incision (1 (IQR = 0-5) vs 0 (IQR = 0-0), p = 0.030). According to symptoms and post-voiding residual measurements, myogenic failure in adults seems to be rare. Conclusions: LUTS are common, but severe symptoms referring to myogenic failure are rare in men treated for PUV in childhood. The specific reasons for LUTS are difficult to indicate and even the sickest children do not necessarily have LUTS in adulthood.

The aim of this study was to evaluate the functional outcomes and urodynamic findings after laparoscopic sacrocolpopexy (LSC) in patients with stages II–IV pelvic organ prolapse (POP). In this single-center prospective study, we evaluated 63 women (mean age 62.5 ± 7.5 years) women with symptomatic and advanced POP (stage II–IV) who underwent LSC without concomitant anti-incontinence surgery. The preoperative evaluation incuded history, clinical examination, and urodynamic testing. Women were followed up at 1, 3, 6, and 12 months after surgery and then annually using history, examination, and uroflowmetry. At 6 months, we performed urodynamic testing. To evaluate urinary symptoms, we used the Urogenital Distress Inventory (UDI)-6 questionnaire before and 6 months after surgery. Median follow- up was 22 months (range 8–48). After surgery, maximum flow (Qmax) significantly improved compared with baseline (14.17 ± 2.3 vs 27 ± 8.4 ml/s; p = 0.02), and the percentage of patients with elevated postvoid residual (PVR) significantly decreased (33.3% vs 11.1%; p = 0.001). Detrusor overactivity and bladder outlet obstruction disappeared in 73.6% and 85.7% of patients, respectively, while detrusor underactivity persisted in 66.6% of women. Twenty women (31.7%) reported stress urinary incontinence (SUI) before surgery (14 clinically evident and 6 as occult form), which persisted in only 7/20 (11%) patients following LSC, with no de novo cases. The most common preoperative symptoms were voiding symptoms, present in 42/63 (66.6%) patients, which resolved in 36 (85.7%). The overactive bladder syndrome disappeared in 60% of women, with no de novo cases. Results were reflected by a significant decrease in UDI-6 score from a median of 16 (0–45) at baseline to 5.5 (0–17) at the final follow-up (p = 0.001). The domain on storage symptoms (median 3 vs 1) and voiding symptoms (median 3 vs 1) of UDI-6 showed an improvement after surgery (p = 0.001). The urodynamic finding showed that LSC in women with advanced POP provides good functional outcomes.

OBJECTIVES To investigate the impact of preoperative detrusor underactivity (DU) on serial treatment outcomes over the course of 5 years after photovaporization (PV) or holmium laser enucleation (HoLEP) in patients with benign prostatic hyperplasia (BPH), to compare its impact after PV vs HoLEP, and to identify predictors of long-term lower urinary tract symptoms (LUTS) improvement. MATERIALS AND METHODS This study involved 245 patients with BPH who had complete 5-year follow-up data (PV using 120W-HPS, n = 143, HoLEP, n = 102), grouped as follows: PV-HPS-DU(+), n = 114; PV-HPS-DU(-), n = 29; HoLEP-DU(+), n = 56; and HoLEP-DU(-), n = 46. Bladder contractility index (BCI) < 100 was regarded as DU. Serial treatment outcomes for the International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry and serum PSA level at 6 months, and at 1, 2, 3, 4 and 5 years after surgery, were compared among the groups. LUTS improvement was defined as a reduction in total IPSS of ≥50% relative to baseline. RESULTS Improvement in total IPSS, quality of life (QoL) index and post-void residual urine volume (PVR) in the PV-HPS-DU(+) and PV-HPS-DU(-) groups were maintained up to 5 years after PV, except for maximum urinary flow rate (Qmax ) and bladder voiding efficiency. In the HoLEP-DU(+) and HoLEP-DU(-) groups, improvements in all outcome variables were maintained up to 5 years after HoLEP. Deteriorations in subtotal voiding symptom score, total IPSS and Qmax with time during the long-term period after surgery were more pronounced in the PV-HPS-DU(+) and HoLEP-DU(+) groups than in the PV-HPS-DU(-) and HoLEP-DU(-) groups. Reductions in subtotal voiding symptom score, total IPSS, QoL index, and serum PSA were greater in the HoLEP-DU(+) group than in the PV-HPS-DU(+) group throughout follow-up. The type of surgery (HoLEP vs PV) and higher baseline BCI were independent predictors of LUTS improvement at 5 years after surgery. CONCLUSION Generally, improvement of micturition symptoms, QoL and PVR in patients with DU appears to be maintained up to 5 years after PV or HoLEP. Deterioration of voiding symptoms and urinary flow rate at long-term follow-up visits after PV or HoLEP was more pronounced in patients with LUTS/BPH with DU than in those without DU. Patients with BPH with DU may benefit from more complete removal of prostatic adenoma by HoLEP and greater baseline bladder contractility in terms of micturition symptoms and QoL.

OBJECTIVES: To create a rat model for neurogenic detrusor underactivity (DU) by bilateral pelvic nerve crush injury (BPNI) and to study temporal changes in detrusor contractility and morphology. METHODS: Male Sprague-Dawley rats were subjected to BPNI or sham surgery and evaluated 1, 3 and 9 weeks after surgery. Bladder function was determined in vivo by awake cystometry, micturition pattern analysis and 24-hours urine collection. Bladders were harvested for in vitro pharmacological investigation by isometric tension recording. Bladders and major pelvic ganglia were investigated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and histochemistry. RESULTS: Overflow incontinence was observed 1 week after BPNI. At 3 and 9 weeks after BPNI, rats showed a bladder phenotype characteristic for DU with increased post-void residuals, reduced voiding efficiencies and lower maximum pressures. In isolated bladder strips, contractile responses to potassium chloride (KCl), carbachol and α,β-methylene adenosine 5'-triphosphate (α,β-mATP) were preserved. On the other hand, neural induced contractility was reduced after BPNI, in line with reduced expression of protein gene product 9.5 and choline acetyltransferase in the major pelvic ganglion 1 week after BPNI. Bladder-to-body weight ratio and detrusor thickness increased following BPNI, indicating detrusor hypertrophy to compensate for the reduced neural input. CONCLUSIONS: BPNI induces a rat model for neurogenic DU. In this model, the detrusor maintains its contractility but denervation of the detrusor was observed. This article is protected by copyright. All rights reserved. ispartof: BJU Int vol:123 issue:5A pages:E86-E96 ispartof: location:England status: Published online

Introduction:To check evidence that symptoms identical with those constituting “underactive bladder” (UAB) and “overactive bladder” (OAB) are caused by apical prolapse and cured by repair thereof. Material and Methods: After repair of apical prolapse by mesh tape reinforcement of lax uterosacral ligaments (USL) data form 1,671 women were retrospectively examined to determine the presence of OAB and UAB symptoms and to check, how many were cured surgically. Thereby 3 different techniques were performed: elevate (n = 277), “Posterior IVS” (n = 1,049), and TFS cardinal (CL)/USL (n = 345). Results: Symptoms identical with those comprising UAB and OAB were cured in up to 80% of cases following surgical repair of the CL/USL complex. Conclusions: These symptoms may be consistent with symptoms of the posterior fornix syndrome, which comprises 4 main symptoms: micturition difficulties, urge/frequency, nocturia, chronic pelvic pain, all consequent on USL laxity. Surgical cure of OAB and UAB is inconsistent with existing definitions, which imply pathogenesis of the detrusor muscle itself. A reconsideration and reformulation of existing definitions may be required. Altering UAB definition to “bladder emptying difficulties” and return to former definitions for OAB such as “detrusor” or “bladder instability” may help to restore compatibility with surgical cure of these conditions.

Objective The aim of this study is to investigate the treatment outcome in men with detrusor underactivity (DU) and voiding dysfunction who underwent transurethral resection or incision of the prostate (TURP or TUIP). DU usually affects decision making whether bladder outlet surgery is necessary. Materials and Methods A total of 60 men with urodynamic DU and voiding dysfunction who underwent TURP or TUIP from 1998 to 2015 were retrospectively analyzed for their treatment outcome after follow-up for more than 1 year. DU was defined as urodynamic evidence of low detrusor pressure ( 300 mL, and a voiding efficiency (VE) of 50% after treatment. Predictive factor for a successful outcome was also analyzed. Results At a mean follow-up of 31 months, 49 (81.7%) patients had achieved a satisfactory treatment outcome. Among the patients who received TURP and TUIP, 38/44 (86.4%) and 11/16 (68.8%) had satisfactory outcome, respectively. The satisfactory group had significantly higher detrusor pressure and greater bladder compliance at baseline than the unsatisfactory group. There was significant improvement in the urodynamic parameters after treatment in the satisfactory group. Among the patients with satisfactory outcome, 34 (69.4%) patients had recovery of detrusor function within 3 months. Conclusion Active surgical treatment such as TURP or TUIP results in recovery of VE and detrusor function within 3 months after treatment in the majority of patients with DU.

Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We previously discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function, sensory nerve activity, and bladder wall remodeling were assessed in C57BL/6 and TRPV1 knockout mice exposed to intensified social stress using conscious cystometry, ex vivo afferent nerve recordings, and histology. Intensified social stress increased void volume, intermicturition interval, bladder volume, and bladder wall collagen content in C57BL/6 mice, indicative of bladder wall remodeling and underactive bladder. However, afferent nerve activity was unchanged and unaffected by the TRPV1 antagonist capsazepine. Interestingly, all indices of bladder function were unchanged in TRPV1 knockout mice in response to social stress, even though corticotrophin-releasing hormone expression in Barrington’s Nucleus still increased. These results suggest that TRPV1 channels in the periphery are a linchpin in the development of stress-induced bladder dysfunction, both with regard to increased sensory outflow that leads to overactive bladder and bladder wall decompensation that leads to underactive bladder. TRPV1 channels represent an intriguing target to prevent the development of stress-induced bladder dysfunction in children.

Context Detrusor underactivity (DUA) is a common but relatively under-researched bladder dysfunction. Underactive bladder (UAB) is the symptom-based correlate of DUA. Recently, there has been renewed interest in this topic. Objective To systematically review and summarise the most recent literature and discuss this in the context of what is already known. Evidence acquisition A systematic review of the literature was performed in December 2017 using Medline and Scopus databases. Separate searches of each database used a complex search strategy including “free text” protocols. Search terms included “underactive bladder”, “detrusor underactivity”, “acontractile bladder”, “detrusor failure”, “detrusor areflexia”, “atonic bladder”, “chronic retention”, and “impaired bladder contractility”. Evidence synthesis The initial search retrieved a total of 1690 studies; of these 44 were included in the final analyses. Conclusions Although there has been an expansion in the literature concerning all aspects of DUA and UAB, knowledge on its epidemiology and aetiopathogenesis is still lacking; there remains a need to develop accurate reproducible diagnostic criteria and effective treatments, in particular drug therapies. Patient summary Recently, there has been renewed interest in underactive bladder with expanding research in this area. The lack of simple, reproducible, noninvasive diagnostic criteria has precluded an accurate estimation of the magnitude of the problem. Recent studies have highlighted the potential role of impaired bladder blood supply in causing bladder underactivity.

International audience; 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.

OBJECTIVES: Detrusor underactivity is diagnosed using urodynamic testing. We hypothesized that nocturia is associated with detrusor underactivity. METHODS: We performed a retrospective chart review of all women who underwent urodynamic testing at our institution between 2016 and 2018. Uroflowmetry and pressure-flow study parameters were compared between women with nocturia (≥ 2 voids/night) and without nocturia (0–1 void/night). Detrusor underactivity was diagnosed using three different criteria: Bladder voiding efficiency < 90%, bladder contractility index < 100, and a composite of three urodynamic measures (Gammie criteria). RESULTS: Of 358 women, 172 (48%) were in the nocturia group and 186 (52%) in the no nocturia group. On uroflowmetry, median postvoid residual volume was similar (20 mL) in both groups. Median maximum flow rate (15 versus 17 mL/s, p < 0.05) and average flow rate (6 mL/s versus 7 mL/s, p < 0.05) were significantly lower in the nocturia compared to the no nocturia group. During pressure-flow study, a significantly greater proportion of women with nocturia were unable to void around the catheter (30% versus 27%, p < 0.01). The overall rate of detrusor underactivity varied with the criteria used: bladder voiding efficiency (54%), bladder contractility index (41%), and Gammie criteria (7%). The rate of detrusor underactivity using bladder voiding efficiency criteria was significantly higher in the nocturia group (63% versus 48%, p < 0.01), but no significant differences were noted using the other criteria. CONCLUSION: Nocturia is associated with reduced voiding efficiency in women. The diagnosis of detrusor underactivity using urodynamics is challenging.

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.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.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.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.

To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS‐EMG) was performed. A total of 33 female Sprague Dawley rats aged 3 months (young rats), 12 months (middle‐aged rats), and 24 months (aged rats) were used. Bladder activity was evaluated using continuous cystometry. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP in isovolumetric conditions under urethane anesthesia in each group. Additionally, EUS‐EMG activity was monitored under the same conditions. In continuous cystometry, the amplitude of bladder contractions was not different among the three groups; nevertheless, residual urine volume was significantly increased in middle‐aged and aged rats, as compared in young rats. With respect to UPP, the change in UPP was significantly smaller in aged rats (60%) and middle‐aged rats (64%) than in young rats. Furthermore, the mean amplitude of high‐frequency oscillations of the EUS was significantly lower in aged (61%) and middle‐aged rats (70%) than in young rats. EUS‐EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle‐aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra., To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS‐EMG) was performed. The amplitude of bladder contractions was not different among young, middle‐aged, and aged rats; nevertheless, residual urine volume was significantly increased in middle‐aged and aged rats and the change in UPP was significantly smaller in aged rats. In histological findings, EUS hypotrophy was observed in aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra.

Bacterial infection may have a pathophysiological role in refractory Detrusor Overactivity (DO). The aim of this study was to observe any impact of antibiotic therapy upon bacterial colonization of urothelial cells, and to determine whether a relationship existed between colonization and symptom severity. Mid-stream urine samples were collected as part of a clinical trial of antibiotics in women with refractory DO. Wright stained urothelial cells were categorized according to the degree of bacterial colonization as; ‘clear’ (free of bacteria), or as associated with bacteria that were ‘adjacent’ to the cell or ‘intracellular’ at low or high density. The average percentages were compared with routine microbiology cultures, over the 26 week trial, and with patient clinical outcome measures of DO severity. In patients receiving placebo, ‘high-density intracellular bacteria’ significantly increased during urinary tract infection (P = 0.0008). In antibiotic patients, ‘clear’ cells were more prevalent. Amoxicillin & Clavulanic Acid significantly decreased bacterial colonization within urothelial cells, suggesting that these antibiotics possess the greatest intracellular efficacy. ‘High-density intracellular bacteria’ positively correlated with symptom severity, measured by leakage on pad test (P = 0.014), leaks per day (P = 0.004), and voids per day (P = 0.005). Thus, by decreasing high density intracellular bacteria, antibiotic treatment may improve the refractory DO condition.

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly ( P < 0.05) increased bladder capacity while PNS at 4 T also significantly ( P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly ( P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly ( P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler’s syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler’s syndrome.

Surgical intervention for benign prostatic enlargement (BPE) is typically reserved for those who fail medical therapy (i.e., α-blocker or 5-α reductase inhibitor treatment). We conducted a systematic review to determine whether timing of surgical intervention for BPE affects patient outcomes. The studies we reviewed suggested that patients who undergo surgical intervention for BPE after failing medical therapy may have worse outcomes. Increased age, worsened bladder function, and worse overall health may contribute to worsened outcomes. To date, there are few high-quality studies on the timing of surgical intervention for BPE in the literature. Further prospective trials are needed to determine ideal timing for intervention.

Metabolic Syndrome (MetS) has detrimental effects on the bladder, including detrusor underactivity. The progression and mechanism of disease are poorly understood. A swine model for diabetic bladder dysfunction (DBD) was established because of the pig's human-sized bladder and its ability to develop MetS by dietary modification alone. The hypothesis of this study is that this swine model will demonstrate oxidative stress associated with MetS, which contributes to both bladder fibrosis and detrusor underactivity (DU). Ossabaw pigs underwent dietary modification consisting of a hypercaloric, atherogenic diet for 10 mo to induce MetS, and were compared with a group of control (lean) pigs. Urodynamic studies were performed in both groups to confirm DU. Thiobarbituric acid reactive substances (TBARS) detected in the urine were used to measure oxidative stress activity in the urinary tract, and urinary IL17a was used to detect profibrotic activity. MetS was confirmed by assessing body weight, blood pressure, glucose tolerance, total cholesterol, and triglycerides. The MetS group exhibited an increase in the relative levels of urinary TBARS and IL17a. Bladder pressures at capacity were lower in the MetS group, suggesting DU. Histologic analysis of a cohort of control (lean) and MetS pigs revealed that as compared with the control pigs, the MetS pigs had significantly more collagen in the muscularis layer, but not in the submucosa or mucosa layer. In conclusion, the Ossabaw pig model for diet-induced MetS is associated with oxidative stress and profibrotic activity in the bladder, which results in DU. This has previously been shown in mice and rats, but never in pigs. This novel model will better represent human MetS and DBD because the mechanism and size of the pig bladder more closely resemble that of a human, resulting in a more valid model and facilitating further study into the signaling mechanisms responsible for this impairment.

To investigate the effect of detrusor underactivity on the efficacy of TURP in patients with benign prostate obstruction. A retrospective study of 350 patients with benign prostate obstruction who underwent TURP was carried out. Different degrees of bladder outlet obstruction were grouped by the bladder outlet obstruction index. ROC curves were used to calculate the optimal cut-off point for the bladder contractility index used to divide the DU patients into mild DU and severe DU patients. The effect of DU on the efficacy of TURP in benign prostate obstruction patients was studied by comparing the subjective and objective parameters preoperatively and 3 months postoperatively between severe DU, mild DU and non-DU benign prostate obstruction patients in two obstruction groups (20 ≤ BOOI

OBJECTIVES To identify the prevalence and predictors of postoperative detrusor underactivity during the early postoperative period after robot-assisted radical prostatectomy. METHODS We carried out a prospective observational study of 64 patients scheduled for robot-assisted radical prostatectomy using urodynamic study before and 1 month after robot-assisted radical prostatectomy. Detrusor underactivity was defined as maximum flow rate ≤15 mL/s and detrusor pressure at maximum flow rate ≤25 cmH2 O during voiding. Incidences of pre- and postoperative detrusor underactivity were assessed, and predictors of postoperative detrusor underactivity were determined using uni- and multivariate logistic regression analyses. Factors comprised patient characteristics (age, prostate weight etc.), operative factors (surgical duration, nerve sparing etc.) and preoperative urodynamic study parameters (maximum flow rate, bladder contractile index etc.). RESULTS Pre- and postoperative detrusor underactivity at 1 month after robot-assisted radical prostatectomy were detected in one patient (1.6%) and 24 patients (37.5%), respectively. Univariate analysis selected preoperative maximum flow rate (P = 0.02), detrusor pressure at maximum flow rate (P = 0.04) and bladder contractile index (P

Background Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. Objectives The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. Design This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Setting Urology departments of 26 NHS hospitals in England. Participants Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Interventions Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). Main outcome measures The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. Results A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (–0.33, 95% CI –1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43–44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. Limitations The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Conclusions Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Future work Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Trial registration Current Controlled Trials ISRCTN56164274. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

Aim To examine the symptoms and noninvasive test parameters that clinically differentiate detrusor underactivity (DU) from bladder outlet obstruction (BOO) without using a pressure-flow study (PFS) in male patients with lower urinary tract symptoms. Methods We examined 909 men who underwent PFS and also had the following data: International Prostate Symptom Score (IPSS), free uroflowmetry, postvoid residual (PVR), and prostate volume (PV). Using these data, significant symptoms and noninvasive test parameters that clinically differentiate DU from BOO were examined. Results Significant parameters between DU patients and BOO patients were older age, smaller PV, and lower urgency symptom score (IPSS Q4). Optimal cutoff values were determined using receiver operating characteristic curves (≥74 years old, PV ≤ 34.8, and IPSS Q4 ≤ 1) and patients were categorized on the basis of the number of significant factors. The probability of DU or BOO in patients with three significant factors were 77% and 34%, respectively. Conclusion Three factors (older age, smaller PV, and fewer urgency symptom) were the predictive factors to differentiate DU from BOO, which might be useful for estimating the probability of DU in clinical practice without a PFS.

The goal of the presented protocol was to establish a detrusor underactivity (DU) model in the rat through conus medullaris transection. Laminectomy was performed in a total of 40 female Wistar rats (control group: 10 rats; test group: 30 rats) weighing 200–220 g, and the conus medullaris was transected at the L4‒L5 level in the test group. All the rats were housed and fed under the same environmental conditions for six weeks. In the test group, urine voiding was performed twice daily for six weeks, and mean residual urine volume was recorded. A cystometrogram was performed in both groups. Maximum cystometric capacity (MCC), detrusor opening pressure (DOP), and compliance of the bladder were recorded and calculated. The test group showed significant urinary retention after the surgery, both during and after the spinal shock. However, no abnormality was observed in the control group. When compared to the control group, the MCC and compliance of bladder in the test group was significantly higher than that of the test group (3.24 ± 2.261 mL versus 1.04 ± 0.571 mL; 0.43 ± 0.578 mL/cmH2O versus 0.032 ± 0.016 mL/cmH2O), whereas DOP in the test group was lower than control (20.28 ± 14.022 cmH2O versus 35 ± 13.258 cmH2O). This method of establishing an animal model of DU by the conus medullaris transection offers an excellent opportunity to understand DU’s pathophysiology in a better manner.

INTRODUCTION Since 2011 we have been following prospectively myelomeningocele patients treated in utero with particular interest to patients with sphincter weakness/deficiency. We investigated the changes of bladder pattern and upper urinary tract with time in children who underwent in utero repair and had low-pressure incontinence based on urodynamic evaluation (UE). MATERIALS AND METHODS From the 120 patients in our database, 117 had at least one UE. Of these, 30 were classified as incontinent when leaking at low pressure (

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help in the development of new treatments by identifying mechanistic targets. In this work, we studied the relationship between age and systems-level function of the LUT and tested the hypothesis that aging is related to weakening of reflexes that control voiding. Three groups of anesthetized female rats, young (4–7 mo old), mature (11–14 mo old), and old (18–24 mo old), were used to quantify the effect of aging on LUT reflexes. A double-lumen catheter enabled us to control the bladder volume and urethral flow rate independently, under quasi-isovolumetric bladder conditions. We systematically investigated the reflex bladder contractions evoked by combinations of rates of urethral infusion and bladder fill volumes as a function of age. Urethral infusion with the same flow rate evoked bladder contractions (via the augmenting reflex) in old animals less often than in younger animals. Furthermore, old animals needed more fluid in their bladders (relative to their bladder capacity) before urethra flow-evoked bladder contractions could be triggered at all, suggesting a delay in the switch of the LUT to “voiding mode.” Old rats also showed longer and weaker bladder contractions than young or mature rats. Taken together, this suggests there is an age-related functional weakening and loss of sensitivity in LUT reflexes, which may contribute to age-related UAB symptoms.