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The heart and bladder share physiological biomechanical determinants of contraction. Heart failure (HF) and myogenic underactive bladder (mUAB) also share similarities in their pathophysiology. In both cases there is muscle injury that is directly linked to disease stage. In the final stage, both myocardium and detrusor show marked fibrosis and lower contractility. While HF has an established pharmacological treatment, there are still no effective drugs for mUAB. This mini-review explores the similarities between HF and mUAB and suggests that, as in HF, SGLT2 inhibitors may also have a beneficial role in mUAB. PATIENT SUMMARY: To date, there is no treatment for underactive bladder caused by problems with the bladder muscle (mUAB). We review similarities between this condition and heart failure and hypothesize that a recent drug class with striking results in heart failure might also have a beneficial role in mUAB.

Purpose This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB). Methods After 2–4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety. Results Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred. Conclusion Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU. Registration ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.

To investigate the association between urodynamic findings and lower urinary tract symptoms (LUTS) before and after surgical treatment of pelvic organ prolapse (POP).Seventy-four patients with stage II or more anterior POP associated with LUTS and eligible for surgical repair of POP were included in this prospective study. All cases had clinical evaluation and urodynamic testing (UDS) before and 6 months after surgical repair of POP.Mean age was 45 ± 9 years. Mean BMI was 28 ± 6 kg/mPatients had significant improvement in LUTS after POP surgery with or without an anti-incontinence procedure. Detrusor underactivity was associated with persistence of voiding LUTS. Meanwhile, preoperative DO and post-void residual urine volume were of limited prognostic value.

To search for independent predictors for distinguishing bladder outlet obstruction (BOO) and detrusor underactivity (DU) in female patients with voiding difficulty.A retrospective patient file review was performed of 918 female patients with lower urinary tract symptoms. After exclusion criteria, 148 patients with voiding difficulty were eligible for the study. Patients were classified as having BOO and DU based on urodynamic BOO and DU definitions. The symptoms, patient characteristics, the patterns of free urine flow, and detrusor voiding pressure curves were compared between 2 groups.Of 148 patients with a median age of 53 (18-86), 42 (28,4%), 37 (25%), 69 (46,6%) patients had a urodynamic diagnosis of BOO, DU, and unclassified P/F study respectively. Multivariate logistic regression analysis results showed that the symptom of weak urine stream [P = .015 OR = 7.07 CI(1,47-34,0)], the negative provocative stress test [P = .038 OR = 7.32 CI(1,12-47,83)], the continuous detrusor voiding pressure and the prolonged/tailed shaped free urine flow curve patterns [P.001 OR = 2,99 CI(1,66-5,38)] were the independent predictors of BOO. Sensitivity and specifity values for prolonged/tailed to predict BOO were 82.5 and 60% respectively.The continuous detrusor voiding pressure and the prolonged/tailed shaped free urine flow curve patterns were found to be useful independent predictors for distinguishing BOO from DU in female patients with voiding difficulty. In addition, the symptom of weak urine stream, and the negative provocative stress test may be of beneficial use.

The coexisting overactive-underactive bladder (COUB) syndrome could be related to the increased urethral resistance caused by severe pelvic organ prolapse (POP). We aimed to evaluate the clinical and urodynamic findings of patients with COUB and/or detrusor overactivity-underactivity (DOU) in a cohort of patients scheduled for POP surgery and the possible risk factors of COUB after surgery.This retrospective study analyzed all patients who underwent POP repair between 2008 and 2013, excluding women with a history of pelvic floor surgery. Patients were divided into COUB and non-COUB according to baseline symptoms and into DOU and non-DOU based on urodynamic findings. A multivariate model was performed to identify risk factors for COUB symptoms after surgery.A total of 533 women underwent POP surgery. Preoperatively, patients with COUB had more severe anterior compartment prolapse (Pelvic Organ Prolapse Quantification staging system Aa point, P = 0.008) and more frequently had overactive bladder compared with controls (P = 0.023). The rate of COUB decreased significantly after surgery. Preoperative opening detrusor pressure resulted as the only independent predictor of postoperative COUB symptoms (P = 0.034).POP is a valid pathogenetic model for COUB development. POP repair induced a significant decrease in COUB symptoms with low opening detrusor pressure resulting as the only independent predictor of postoperative COUB.

AIM: The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB).METHODS: A randomized, double-blind, placebo-controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4-week oral once-daily administration of 100 mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVRC2 ). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressure-flow studies were performed in a subgroup.RESULTS: One hundred and thirty-five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVRC2 was -40.0 ml (ASP8302) versus -35.0 ml (placebo) and the difference between groups was -5.0 ml (p = 0.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (Qmax ) and detrusor pressure at Qmax (Pdet.Qmax ) increased (mean difference in change ASP8302 vs. placebo: 3.8 ml/s, p = 0.031 and 12.7 cm H2 O, p = 0.034, respectively). Urinary incontinence episodes/24 h decreased in males with preexisting incontinence (mean difference: -0.35; p = 0.028). The incidence of adverse events was similar between study groups (ASP8302: 33.3%, placebo: 31.4%). In the included subjects, both baseline urine flow and bladder voiding pressure was low. Compared with PVR, simultaneous BVE measurements were more consistent between various methods (spontaneous vs. standardized bladder filling, catheterization vs. ultrasound [US]).CONCLUSIONS: ASP8302 was safe and well tolerated in patients with UAB identified by nonurodynamic clinical criteria, but it did not show efficacy in the primary endpoint. However, in males it showed improvement of symptoms and functional parameters. BVE (using US) is a more optimal outcome measure than PVR in UAB.

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.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.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.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.

To investigate the clinical features of detrusor underactivity (DU) in elderly men without neurological disorders.A total of 336 men aged ≥50 years without neurogenic disorders who underwent pressure flow studies and who had DU or bladder outlet obstruction (BOO) were reviewed retrospectively. According to the bladder contractility index (BCI) and the BOO index (BOOI), the subjects were classified into the following three groups: (a) pure DU group, BCI 100 and BOOI 40; (b) DU + BOO group, BCI 100 and BOOI ≥ 40; and (c) pure BOO group, BCI ≥ 100 and BOOI ≥ 40. Subjective and objective parameters were compared among the three groups, and the predictors for pure DU were evaluated by multivariate analysis.Of the 336 patients, 205 who met the study criteria were included in the analysis: 63 (30.7%) with pure DU, 48 (23.4%) with DU + BOO, and 94 (45.9%) with pure BOO. The proportion of the pure DU group increased with increasing age. Prostate volume was the lowest in the pure DU group. Frequency, urgency on the International Prostate Symptom Score (IPSS), and the IPSS storage subscore were the lowest in the pure DU group. Multivariate analysis showed that age (odds ratio [OR] 1.114 [95% CI, 1.032-1.203], P = .005), prostate volume (OR 0.968 [95% CI, 0.949-0.987], P = .001), and urgency (OR 0.623 [95% CI, 0.431-0.900], P = .012) were predictors of pure DU.Older age, smaller prostate volume, and less urgency may be clinical features of pure DU.

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

It is not possible to diagnose the cause of voiding difficulty on the basis of a history alone. Bladder underactivity and bladder outlet obstruction cause similar voiding symptoms and also can be associated with storage symptoms. In this mini-review, we consider the factors associated with making a symptomatic diagnosis of either underactive bladder or bladder outlet obstruction. PATIENT SUMMARY: There is overlapping of symptoms for different urinary problems. To differentiate between underactive bladder and bladder outlet obstruction as the underlying cause of lower urinary tract symptoms, an invasive urodynamic study of the bladder is often required.

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.

Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alphaChanges in intraurethral pressure (IUP) induced by midodrine (alphaBoth silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction.Alpha

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.