Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.

BACKGROUND AND PURPOSE: Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS. EXPERIMENTAL APPROACH: Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8-20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60-2770 or a combination of celecoxib and BAY 60-2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically. KEY RESULTS: Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60-2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60-2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation. CONCLUSION AND IMPLICATIONS: Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60-2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.

The inhibitory effect of trimetazidine on detrusor contractility - a potential repositioning of trimetazidine for the treatment of overactive bladder.

OBJECTIVES: This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action. METHODS: We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca2+ levels in fura-2-loaded A7r5 cells. KEY FINDINGS: TMZ (300 or 1000 µM) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10-1000 µM) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K+ channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 µM) reduced both the CaCl2-induced contraction of depolarized DSM strips under Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells. CONCLUSIONS: TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca2+ transients and K+ channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.

Therapeutic effect of modulating the NLRP3-regulated transforming growth factor-ß signaling pathway on interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder with complex pathogenesis and lacks effective treatment. Chronic inflammation is the main pathogenesis of Hunner-type IC/BPS. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related transforming growth factor-ß (TGF-ß)/Smad signaling pathway plays a crucial role in inflammation-related tissue fibrosis. Lipopolysaccharide (LPS) and protamine sulfate (LPS/PS) were instilled into the mouse bladder twice a week for 5 consecutive weeks to establish a chronic inflammation-induced IC/BPS model (LPS/PS model). Following LPS/PS treatment, curcumin (oral, 100 mg/kg; a potent NLRP3 modulator) was administered for 2 weeks in the curcumin treatment group, and normal saline was used for the sham group. Bladder function was evaluated by performing the voiding spot assay and examining the status of urothelial denudation and fibrosis in bladder tissues. The expression of NLRP3 inflammasome, interleukin-1ß, TGF-ß, Smad, vimentin, and E-cadherin in bladder tissues was evaluated through immunohistochemistry staining. Results revealed that the repeated instillation of LPS/PS leads to voiding dysfunction, bladder urothelium denudation, and detrusor muscle fibrosis through the upregulation of the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway and the increased epithelial-mesenchymal transition process in bladder tissues. The downregulation of the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway in bladder tissues through curcumin effectively mitigated bladder injury in the LPS/PS model. In conclusion, the NLRP3 inflammasome/IL-1ß-related TGF-ß/Smad pathway plays a crucial role in bladder injury in the LPS/PS model, and modulation of this pathway, such as by using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced IC/BPS.

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding.

Dysfunctional voiding (DV), a voiding dysfunction due to hyperactivity of the external urethral sphincter or pelvic floor muscles leading involuntary intermittent contractions during voiding, is not uncommon in neurologically normal women with lower urinary tract symptoms (LUTS). We aimed to investigate the therapeutic efficacy of biofeedback pelvic floor muscle training (PFMT) in female patients with DV and to identify the therapeutic efficacy. Thirty-one patients diagnosed with DV. All participates completed the 3-month biofeedback PFMT program, which was conducted by one experienced physiotherapist. At 3 months after treatment, the assessment of treatment outcomes included global response assessment (GRA), and the changes of clinical symptoms, quality of life index, and uroflowmetry parameters. 25 (80.6%) patients had successful outcomes (GRA ≥ 2), and clinical symptoms and quality of life index significantly improved after PFMT. Additionally, uroflowmetry parameters including maximum flow rate, voided volume, voiding efficiency, total bladder capacity, voiding time, and time to maximum flow rate significantly improved after PFMT treatment. Patients with the history of recurrent urinary tract infection in recent 1 year were found to have unsatisfied therapeutic outcomes. In conclusion, biofeedback PFMT is effective in female patients with DV with significant improvements in clinical symptoms, quality of life, and uroflowmetry parameters. The history of urinary tract infection in recent 1 year is a negative predictor of successful outcome.

Effect of Transurethral Resection of the Prostate on Urodynamic Parameters in Patients with Benign Prostatic Enlargement with Upper Urinary Tract Dilatation.

OBJECTIVE: To evaluate the urodynamic outcomes of transurethral resection of the prostate (TURP) in patients of benign prostatic enlargement (BPE) with upper urinary tract dilatation and correlate with International Prostate Symptoms Score (I-PSS). METHODS: In this prospective study, patients of BPE with upper urinary tract dilatation from July 2017 to June 2019 were enrolled. At presentation, detailed I-PSS, ultrasonography abdomen, serum creatinine, and serum PSA were recorded. All the patients were catheterized and observed for postobstructive diuresis. At 4 weeks, repeat ultrasound and serum creatinine were recorded. Urodynamic study (UDS) was performed after ensuring sterile urine culture. Patients underwent TURP as per the standard technique. A repeat UDS was performed after 3 months, and analysis was done. RESULTS: Forty-four patients were enrolled of which data of 37 patients were analyzed. In the filling phase of the UDS, there was a significant decrease in detrusor pressure at the end filling phase from 27 to 9.0 cm H2O after TURP. Maximum cystometric capacity and bladder compliance significantly improved at 3 months following surgery. In the voiding phase, peak flow rate showed a significant increase, postvoid residual urine volume significantly decreased, and peak detrusor pressure marginally decreased following TURP. The I-PSS decreased from 20 ± 8 to 5 ± 6 following TURP. CONCLUSION: High detrusor pressure and reduced compliance is a risk factor for upper urinary tract dilatation. Changes in the bladder dynamics and resolution of hydronephrosis following TURP reflected in the changes in urodynamic parameters and I-PSS.

Detrusor overactivity and underactivity: implication for lower urinary tract symptoms related to benign prostate hyperplasia diagnosis and treatment.

INTRODUCTION: Detrusor underactivity (DUA) and detrusor overactivity (DO) have potential impact on the outcomes of surgery for lower urinary tract symptoms related to benign prostate hyperplasia (LUTS/BPH). EVIDENCE ACQUISITION: We performed a literature search including studies on humans enrolling patients with preoperative urodynamic evidence of DO and/or DUA undergoing LUTS/BPH surgery. Factors that may influence the outcomes of surgery in these patients were evaluated. EVIDENCE SYNTHESIS: In patients with DUA mean bladder contractility index improved from +4 to +44.6, mean total International Prostate Symptom Score (IPSS) improved from -3 to -19.5 points, mean maximum urinary flow (Qmax) improved from +1.4 to +11.7 mL/s, and mean postvoid residual volume (PVR) improved from -16.5 to -736 mL. Older age, lack of obstruction, concomitant DO, lower detrusor contractility and use of transurethral resection of the prostate (TURP) or photovaporization (PV) instead of Holmium laser enucleation of the prostate (HoLEP) were associated with worse outcomes. In patients with DO, the percentage of DO resolution ranged from 57.1% to 83.3%. Mean total IPSS, Qmax, and PVR variations ranged from +0.9 to -15.7 points, from -0.2 mL/s to +14 mL/s, and from -19.6 to -202.5 mL, respectively. Older age, lack of obstruction, terminal DO, low maximum cystometric capacity, early and high amplitude DO, and use of transurethral prostate incision instead of TURP or open adenomectomy were associated with worse outcomes. CONCLUSIONS: In patients with DUA or DO, surgery for LUTS/BPH provides overall good results. However, a number of factors can affect these outcomes.

A Supervised 3 Weeks Test Phase in Sacral Neuromodulation with a 1-Year Followup.

PURPOSE: We sought to determine whether prolonged interventional test phase increases cumulative success rate and compared success rates between early responders (ie within 1 week) and those in need for reprogramming (due to lack of efficacy) of sacral neuromodulation after 1-year followup. MATERIALS AND METHODS: In a single tertiary center prospective study (August 2015 to November 2018) 90 patients refractory to first line treatment were eligible for sacral neuromodulation, including 48 overactive bladder wet (53%), 8 overactive bladder dry (9%) and 34 nonobstructive urinary retention (38%). Patients were evaluated at weekly intervals during test phase and those not successful were reprogrammed. This could be repeated after the second week. Primary outcome was success rate after 3-week test phase and after 1-year followup. Statistical analysis was done by nonparametric tests for numeric (Mann-Whitney U) and categorical (chi2) data. RESULTS: After 3 weeks of test period 56 patients (62%) were considered successful. Prolonged interventional testing increased cumulative success. A 1-year followup showed no significant difference in success rate between early responders and those in need for reprogramming (chi2, p=0.562). There was no difference in age (Mann-Whitney U, p=0.222), sex (chi2, p=0.952) or indication (chi2, p= 0.975). CONCLUSIONS: A 3-week test phase with close followup increases cumulative success rate. During this supervised 3-week test phase 42% of the initial nonresponders after the first week became successful candidates after reprogramming. Patients who required this additional programming did equally as well as those without need for reprogramming. A supervised 3-week test phase is therefore strongly recommended.

National Trends in Neuromodulation for Urinary Incontinence Among Insured Adult Women and Men, 2004-2013: The Urologic Diseases in America Project.

OBJECTIVE: To examine US trends in neuromodulation for urinary incontinence (UI) treatment from 2004 to 2013. METHODS: This study utilized 2 data sources: the Optum© de-identified Clinformatics® Data Mart Database for privately insured adults aged 18-64 years with a UI diagnosis (N≈40,000 women and men annually) and the Medicare 5% Sample for beneficiaries aged ≥65 years with a UI diagnosis (N≈65,000 women and men annually). We created annual cross-sectional cohorts and assessed prevalence of UI-related neuromodulation procedures among men and women separately from 2004 to 2013. Analyses were conducted overall and stratified by age, race/ethnicity, and geographic region. RESULTS: Nearly all neuromodulation procedures occurred in outpatient settings. Sacral neuromodulation (SNM) procedures for UI in both women and men grew steadily from 2004 to 2013, with more procedures performed in women than men. Among women with UI, SNM prevalence grew from 0.1%-0.2% in 2004 to 0.5%-0.6% in 2013. Posterior tibial nerve stimulation (PTNS) experienced growth from 2011 to 2013. Chemodenervation of the bladder with onabotulinumtoxinA (BTX) combined with other injectable procedures (including urethral bulking) remained stable over time. CONCLUSIONS: From 2004 to 2013, SNM procedures remained relatively uncommon but increased consistently. PTNS experienced growth starting in 2011 when PTNS-specific insurance claims became available. BTX trends remain unclear; future studies should assess it separately from other injectable procedures. Neuromodulation has a growing role in UI treatment, and ongoing trends will be important to examine.

Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

BACKGROUND: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment. OBJECTIVE: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging. STUDY DESIGN: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks. RESULTS: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001). CONCLUSION: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

The intracellular Ca2+ release channel TRPML1 regulates lower urinary tract smooth muscle contractility.

TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel that is predominantly localized to the membranes of late endosomes and lysosomes (LELs). Intracellular release of Ca2+ through TRPML1 is thought to be pivotal for maintenance of intravesicular acidic pH as well as the maturation, fusion, and trafficking of LELs. Interestingly, genetic ablation of TRPML1 in mice (Mcoln1-/- ) induces a hyperdistended/hypertrophic bladder phenotype. Here, we investigated this phenomenon further by exploring an unconventional role for TRPML1 channels in the regulation of Ca2+-signaling activity and contractility in bladder and urethral smooth muscle cells (SMCs). Four-dimensional (4D) lattice light-sheet live-cell imaging showed that the majority of LELs in freshly isolated bladder SMCs were essentially immobile. Superresolution microscopy revealed distinct nanoscale colocalization of LEL-expressing TRPML1 channels with ryanodine type 2 receptors (RyR2) in bladder SMCs. Spontaneous intracellular release of Ca2+ from the sarcoplasmic reticulum (SR) through RyR2 generates localized elevations of Ca2+ ("Ca2+ sparks") that activate plasmalemmal large-conductance Ca2+-activated K+ (BK) channels, a critical negative feedback mechanism that regulates smooth muscle contractility. This mechanism was impaired in Mcoln1-/- mice, which showed diminished spontaneous Ca2+ sparks and BK channel activity in bladder and urethra SMCs. Additionally, ex vivo contractility experiments showed that loss of Ca2+ spark-BK channel signaling in Mcoln1-/- mice rendered both bladder and urethra smooth muscle hypercontractile. Voiding activity analyses revealed bladder overactivity in Mcoln1-/- mice. We conclude that TRPML1 is critically important for Ca2+ spark signaling, and thus regulation of contractility and function, in lower urinary tract SMCs.

At-Home Transvaginal Device Following Fractional Carbon Dioxide Laser Treatment for Genitourinary Syndrome of Menopause.

BACKGROUND: Device-based therapeutic approaches have been developed to treat women’s genitourinary post-menopausal symptoms. Fractional carbon dioxide laser resurfacing (FxCO2) has been demonstrated to be safe and effective in the treatment of GSM symptoms, however the results begin to wane by 12-months post-treatment. OBJECTIVE: This study aims at assessing the application of an at-home transvaginal red and infrared light device as a maintenance treatment commencing 12 months following FxCO2 laser treatment for genitourinary syndrome of menopause (GSM). STUDY DESIGN: Subjects completing 12-month follow-up after three fractional CO2 laser vulvovaginal treatments received an at-home device and monitored for GSM symptoms with long-term follow-up to 12 months (2 years post-laser). METHODS: 10 post-menopausal subjects completing 12-months follow-up after three FxCO2 vulvovaginal treatments for GSM were treated with an at-home red and infrared LED device. Treatment consisted of intravaginal application three times per week, and subjects were followed to 1, 3, 6, and 12 months. Subjects completed the vaginal assessment scale subject satisfaction, and QUID to assess for vulvovaginal and stress urinary incontinence (SUI) symptoms. RESULTS: Vulvovaginal symptoms measured by VAS were mean 89% improved at 12-month follow-up after FxCO2 and maintained at 73% improved over baseline (2 years post-laser) following an additional 12 months of at-home transvaginal light therapy (P<0.05). VAS symptoms gradually increased over the 12 months maintenance period by a mean of 17% (P<0.05). Mean subject satisfaction was 0 at baseline, 1.86 at 1 year following FxCO2, and 1.00 after an additional 1 year of at-home light therapy. SUI symptoms as measured by QUID were mean 81% improved at 12-month follow-up after FxCO2and maintained at 38% improved over baseline (2 years post-laser) following an additional 12-months of at-home light therapy (P<0.05). SUI symptoms gradually increased by a mean of 43% over the 12-month maintenance period (P<0.05). CONCLUSIONS: At-home transvaginal red and near infrared light therapy commencing at 12 months post-FxCO2 vulvovaginal treatment in a post-menopausal population maintained statistically significant improvements in vulvovaginal and SUI symptoms over the additional12-month period (2 years post-laser); however, a gradual return of symptoms suggests that laser re-treatment or combination withhormone therapy may be necessary to maintain optimal outcomes.J Drugs Dermatol. 2020;19(11):1076-1079. doi:10.36849/JDD.2020.1012.

Which combination is most effective in women with idiopathic overactive bladder, including bladder training, biofeedback, and electrical stimulation? A prospective randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of single and combined use of biofeedback (BF) and electrical stimulation (ES) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with idiopathic overactive bladder (OAB). MATERIAL AND METHODS: Seventy women were randomized into four groups as follows: Group 1 received BT alone (n = 18), Group 2 received BT + BF (n = 17), Group 3 received BT + ES (n = 18), and Group 4 received BT + BF + ES (n = 17). BF and ES were performed 3 days a week, 20 min a day, a total of 24 sessions for 8 weeks. All women were evaluated in terms of incontinence severity (pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and number of pads), QoL (incontinence impact questionnaire), treatment success (positive response rate), cure/improvement rate, treatment satisfaction (Likert scale), and discomfort level (visual analog scale). RESULTS: At the end of the treatment, severity of incontinence, frequency of voiding, incontinence episodes, and treatment satisfaction significantly improved in Group 3 and Group 4 compared with the other two groups. In Group 3 and Group 4, high statistically significant values were found in cure/improvement and positive response rates as opposed to Group 1 and Group 2. In Group 2 and Group 3, statistically significant improvements were seen in nocturia and QoL compared with Group 1. Moreover, statistically significant improvements in nocturia and QoL were found in Group 4 compared with the other three groups. There was no difference in the discomfort level of application between the groups. CONCLUSION: We conclude that in the first-line conservative treatment of women with idiopathic OAB: (i) adding BF and/or ES to BT increases treatment effectiveness, (ii) clinical efficiency is greater when the combination includes ES, (iii) BT + BF + ES (triple combination) is the most effective treatment option in reducing nocturia and improving QoL.

Sacral Nerve Stimulation in Parkinson's Disease Patients With Overactive Bladder Symptoms.

OBJECTIVE: To assess the efficacy, safety, and outcomes of sacral nerve stimulation (SNS) for Parkinson's disease (PD) patients with overactive bladder symptoms. METHODS: We retrospectively reviewed PD patients who underwent Stage I SNS. Demographics, urodynamic data, and baseline voiding function were analyzed. Efficacy and safety of treatment were determined by rate of progression to Stage II, explantation, and surgical revision. Long-term outcomes were assessed using voiding diaries and/or clinic notes. RESULTS: Sixty percent (9/15) experienced ≥50% improvement in urinary parameters and proceeded to Stage II. There was no significant difference in age, body mass index, comorbidities, PD disease duration, or levodopa equivalent daily dose between successful and nonsuccessful Stage I patients. However, 100% of female patients experienced Stage I success compared to 44% of male PD patients (P = .04). Individuals with >12-month follow-up experienced an average reduction of 6 voids/day. No patients required revision or explantation of their device at latest clinic follow-up (22.2 ± 7.8 months). Higher maximal urethral closure pressures, detrusor pressure at maximum flow rate (PdetQmax), post-void residual volume, and mean bladder outlet obstruction index were observed in the Stage I trial failures. CONCLUSION: At our institution, PD patients have a similar rate of progression to Stage II compared to the general population. SNS is an effective therapy that should be considered among the treatment options for PD patients with overactive bladder symptoms. Urodynamic parameters associated with obstruction may be predictive of SNS failure in PD patients and may help guide patient selection, however further studies are needed.

Hyperbaric oxygen therapy prevents subarachnoid hemorrhage-induced apoptosis and impaired contractility of the rabbit bladder.

AIM: To explore the effects of experimental subarachnoid hemorrhage (SAH) on rabbit urinary bladder and to assess the potential protective effects of hyperbaric oxygen therapy (HBOT). METHODS: A total of 15 male New Zealand white rabbits were divided randomly to one of three groups: group I was spared as the control group (n = 5), group II was exposed to SAH, received no treatment, and acted as the SAH group (n = 5) and group III was exposed to SAH and received five sessions of HBOT (started 12 hours after SAH induction and was given twice daily for the first 2 days and once on the third day) and acted as the treatment group (n = 5). At 72 hours after the SAH induction, bladders from all animals were removed for in vitro organ bath experiments and biochemical analyses. RESULTS: Isometric tension studies revealed that compared to group I, the contractile responses of the strips to carbachol in group II were significantly decreased whereas HBOT restored the contractile responses (P < .05). Caspase-3 and nitric oxide synthase (NOS) activities of bladder tissues were significantly increased in group II when compared with group I, whereas caspase-3 and NOS activities were significantly decreased in the tissues of group III (P < .01). CONCLUSIONS: Subarachnoid hemorrhage stimulates apoptosis of the rabbit bladder and impairs the contractile response of the rabbit bladder to carbachol. HBOT creates a protective effect in rabbit bladder tissues and restores SAH-induced changes.

Contemporary Patterns of Third-line Treatments for Privately Insured Individuals With Overactive Bladder in the United States.

OBJECTIVE: To evaluate utilization of third-line overactive bladder (OAB) treatments including percutaneous tibial nerve stimulation (PTNS), sacral nerve stimulation (SNS), and intradetrusor botulinum toxin A (BTX) among privately insured patients and examine factors associated with their use. MATERIALS AND METHODS: Using MarketScan claims (2015-2017), we identified patients who underwent third-line OAB treatments based on procedure codes. Factors of interest included location, age, health plan, among others. We fit multivariable logistic regression models to estimate associations between pertinent factors with receipt of PTNS and SNS relative to BTX and associations between provider type and practice location with each treatment modality. RESULTS: We identified 7383 patients (mean age 50.9) in our cohort. SNS was used most frequently (n = 3602, 48.8%), while PTNS was used least frequently (n = 955, 12.9%). PTNS patients were more likely to reside in metropolitan areas (vs BTX: OR 1.6, 95%CI 1.3-2.1; vs SNS: OR 2.2, 95%CI 1.7-2.8), be aged 55 years or older (vs BTX: 54% vs 47%, OR 1.6, 95%CI 1.2-2.1; vs SNS: 54% vs 45%, OR 1.6, 95%CI 1.2-2.0), and be covered under a health maintenance organization (vs BTX: 17% vs 10%; vs SNS: 17% vs 10%, P <.01). Urologists were most likely to perform SNS, and gynecologists were most likely to perform BTX. 91% of PTNS procedures were performed in office settings. CONCLUSION: Among patients receiving third-line OAB treatment, PTNS was used infrequently. PTNS utilization was concentrated within urban areas, and among older patients and those covered by cost-conscious health maintenance organizations.

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling.

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.

Assessment and Management of Urinary Dysfunction in 187 Patients with Parkinson's Disease.

BACKGROUND: Urinary dysfunction is common in Parkinson's disease (PD) patients and management options are limited. OBJECTIVE: This study aimed to explore the management of urinary dysfunction by researching the special needs of PD patients. METHODS: PD patients with urinary dysfunction who underwent urodynamic testing were recruited from a single center from October 2013 to February 2019. The urinary symptoms, International Prostate Symptom Score and Hoehn-Yahr scale were evaluated. Management was made at the urologists' discretion with follow-up after three weeks. Urinary symptoms, urodynamics and the management of urinary dysfunction were analyzed. RESULTS: A total of 187 patients with a median age of 66.2 and Hoehn-Yahr scale soccer of 2 were enrolled. Irritative symptoms were more common than obstructive symptoms, while obstructive symptoms were more common in male than female patients, except for incomplete voiding. There were 51% cases of detrusor overactivity, followed by 33% with bladder outlet obstruction, 13% had normal function, 12% had detrusor underactivity, 9% had stress incontinence, 7% had increased bladder sensation and 4% had an acontractile bladder. Tolterodine and tamsulosin were the most common therapeutic agents, respectively prescribed to 38.5% and 27.3% of the patients. Other treatments included catheterization, botulinum toxin A bladder wall injection, transurethral resection of the prostate and urethral dilatation. Urinary symptoms were improved significantly in 74.5% of the patients (p < 0.001), including 27 patients treated with tamsulosin only and 54 patients with tolterodine only. CONCLUSIONS: Urinary symptoms and urodynamics were highly variable in PD patients, indicating that most patients may benefit from personalized management.

Comparative Study of the Effectiveness and Safety of Transurethral Bipolar Plasmakinetic Enucleation of the Prostate and Transurethral Bipolar Plasmakinetic Resection of the Prostate for Massive Benign Prostate Hyperplasia (>80 ml).

BACKGROUND The aim of this study was to compare the clinical safety and effectiveness of transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) vs. transurethral bipolar plasmakinetic resection of the prostate (PKRP) in the treatment of benign prostate hyperplasia (BPH) more than 80 ml. MATERIAL AND METHODS From June 2015 to February 2019, 179 BPH patients with prostate volume greater than 80 ml were enrolled and separated into a PKEP (n=81) group and a PKRP group (n=98). The patients in the 2 groups were followed up for 6 months. We collected and analyzed data from the international Prostate Symptom Score (IPSS), residual urine volume (RUV), quality of life (QOL), maximum urine flow rate (Qmax), and international erectile function index (ILEF-5). The clinical data collected during and after the operation and surgical complications were compared between the 2 groups. RESULTS The PKEP group had significantly shorter operation time, bladder flushing time, indwelling catheter time, and hospitalization time, and has less intraoperative blood loss, intraoperative blood transfusion, postoperative secondary hemorrhage, bladder neck contracture, capsule perforation, and retrograde ejaculation (P<0.05). Compared with the PKRP group, the postoperative IPSS and QOL scores were significantly lower in the PKEP group (P<0.05), while the excision glandular tissue weight and Qmax were significantly improved (P<0.05). There were no significant differences in ILEF-5 scores, RUV, urethral stricture, urinary incontinence, or erectile dysfunction between the 2 groups (p>0.05). CONCLUSIONS PKEP treatment of BPH with a large volume (>80 ml) has the advantages of complete gland resection, good surgical effect, improved surgical safety, and reduced intraoperative and postoperative complications.

Brain activation patterns of female multiple sclerosis patients with voiding dysfunction.

AIMS: We compared brain activation patterns between female multiple sclerosis (MS) patients with voiding dysfunction (VD) and those without. We aim to expand current knowledge of supraspinal correlates of voiding initiation within a cohort of female MS patients with and without VD. MATERIALS AND METHODS: Twenty-eight ambulatory female MS patients with stable disease and lower urinary tract dysfunction were recruited for this study. Subjects were divided into group 1, without VD (n = 14), and group 2, with VD (n = 14), defined as postvoid residual urine of ≥40% of maximum cystometric capacity or need for self-catheterization. We recorded brain activity via functional magnetic resonance imaging (fMRI) with simultaneous urodynamic testing. Average fMRI activation maps (the Student t test) were created for both groups, and areas of significant activation were identified (P < .05). A priori regions of interest (ROIs), identified by prior meta-analysis to be involved in voiding, were selected. RESULTS: Group-averaged blood-oxygen level-dependent (BOLD) activation maps demonstrated significant differences between groups 1 and 2 during initiation of voiding with group 2 showing significantly lower levels of activation in all ROIs except for the left cerebellum and right cingulate gyrus. Interestingly, group 2 displayed negative BOLD signals, while group 1 displayed positive signals in the right and left pontine micturition center, right periaqueductal gray, left thalamus, and left cingulate gyrus. The activation map of group 1 was similar to healthy controls. CONCLUSIONS: Our results support the hypothesis that distinct supraspinal activation patterns exist between female MS patients with VD and those without.