Purine nucleoside phosphorylase as a target for the treatment of interstitial cystitis/bladder pain syndrome with and without Hunner lesions.

Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome (IC/BPS), are difficult to treat, and therapies are limited in number and efficacy. Emerging evidence suggests that alterations in the enzyme purine nucleoside phosphorylase (PNPase) may participate in oxidative injury and cellular damage. PNPase is important for the metabolism of 'tissue-protective' purine metabolites to 'tissue-damaging' purines that generate free radicals. The aim of this study is to test whether patients living with IC/BPS without or with Hunner lesions and irrespective of any therapies exhibit purine dysregulation with higher levels of tissue-damaging purine metabolites as measured by liquid chromatography-tandem mass spectrometry. Our results demonstrate that levels of urotoxic purine metabolites (hypoxanthine and xanthine) in IC/BPS patients with and without Hunner lesions are elevated compared to healthy controls. These findings suggest there may be pathophysiologic commonalities between patient subtypes. Furthermore, the accumulation of uroprotective purines and depletion of urodamaging purines by PNPase inhibition may be therapeutically effective in both groups of patients.

The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner's (HIC) and non-Hunner's IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient's needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition.

Predictive Factors for the Successful Outcome of Urethral Sphincter Injections of Botulinum Toxin A for Non-Neurogenic Dysfunctional Voiding in Women.

PURPOSE: Dysfunctional voiding (DV) is not uncommon in women with non-neurogenic voiding dysfunction. Because of its unknown pathophysiology, effective and durable treatment is lacking. This study aimed to analyze the results of treatment and predictive factors for a successful outcome of botulinum toxin A (BoNT-A) treatment in female patients with DV. METHODS: In total, 66 women with DV confirmed by a videourodynamic study (VUDS) were treated with a BoNT-A injection into the urethral sphincter once (n = 33) or several times (n = 33). VUDS was performed before (baseline) and after the BoNT-A treatment. Patients with a global response assessment of the voiding condition of 2 or 3 and a voiding efficiency (VE) of >20% than baseline were considered to have a successful outcome. The baseline demographics, VUDS parameters, and VUDS DV subtypes were compared between the successful and failed groups. Predictive factors for a successful outcome were investigated by logistic regression analyses. RESULTS: Successful and failed outcomes were achieved in 27 (40.9%) and 39 (59.1%) women, respectively. After BoNT-A injections, the maximum flow rate (Qmax), voided volume, and VE all significantly increased, and the postvoid residual (PVR) was slightly improved. No significant difference in the number of injections and medical comorbidity was found between the groups. However, the successful group had a higher incidence of previous pelvic surgery. No significant difference in the treatment outcome was found among patients with different urethral obstruction sites. Significant improvements in Qmax, voided volume, PVR, VE, and the bladder outlet obstruction (BOO) index were noted in the successful group. A lower VE at baseline and a history of surgery were identified as predictive factors for a successful outcome of BoNT-A injections for treating DV. CONCLUSION: BoNT-A injections into the urethral sphincter can effectively improve VE in 40.9% of women with DV. Women with higher BOO grades and previous pelvic surgery are predicted to have a successful treatment outcome.

Using Urine Biomarkers to Differentiate Bladder Dysfunctions in Women with Sensory Bladder Disorders.

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner's interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management.

Efficacy of Urethral Sphincter Botulinum Toxin A Injection in Patients with Spinal Cord Injury with Dysuria: A Retrospective Cohort Study.

Spinal cord injury (SCI) often leads to neurogenic lower urinary tract dysfunction, causing dysuria and affecting patients' well-being. This study aimed to evaluate the efficacy of a urethral sphincter botulinum toxin A (BoNT-A) injection in patients with SCI and dysuria. This was a retrospective study including 118 patients with SCI who underwent a urethral BoNT-A injection following a standardized protocol for refractory voiding dysfunction. The protocol involved injecting BoNT-A into the urethral sphincter under cystoscopic guidance. Patient demographics, bladder condition parameters, and treatment outcomes were analyzed. Logistic regression and receiver operating characteristic curve analyses were performed to identify predictors of treatment success. Of the 118 patients, 71 (60.1%) showed satisfactory treatment outcomes after the injection. Post-injection status, bladder management, and injection frequency varied significantly among patients with satisfactory and unsatisfactory treatment outcomes. Age, bladder compliance, intravesical pressure, and bladder contractility were indicators of satisfactory outcomes. The first sensation of bladder filling of ≤263 mL, intravesical pressure of ≤28, and bladder contractility index of ≥14 were highly correlated with satisfactory outcomes. A urethral sphincter BoNT-A injection shows promise in managing dysuria in patients with SCI. Understanding bladder condition parameters and patient demographics helps optimize patient selection for this intervention. Further studies are needed to validate these findings and refine treatment protocols.

Impact of Urethral Sphincter Electrophysiology on Botulinum Toxin A Treatment in Women with Non-Neurogenic Dysfunctional Voiding.

Dysfunctional voiding (DV) is an abnormal urethral sphincter activity during voiding in neurologically normal individuals. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to treat DV, but the results have not been completely satisfactory. This study investigated the neurological characteristics of women with DV using the lower urinary tract electrophysiology (EP) study and the therapeutic efficacy of BoNT-A injection. In total, 48 women with DV and 16 women with normal voiding were included. Videourodynamic studies were conducted to diagnose DV before BoNT-A injection. EP studies, including urethral sphincter electromyography, bulbocavernosus reflex, and pudendal nerve conduction velocity, were conducted. Polyphasic motor unit action potentials suggestive of reinnervation were detected in 58.3% of patients with DV and 18.8% of controls (p = 0.001). Significant improvement in the corrected maximum flow rate (cQmax) was observed in patients with reinnervation at 1 and 3 months after BoNT-A injections into the urethral sphincter. Urethral sphincter denervation or reinnervation activity was commonly noted in 62.5% of women with DV. Repeated BoNT-A injections into the urethral sphincter provided effective treatment in 47.9% of patients, with mild improvement in cQmax observed in patients with urethral sphincter reinnervation. However, the improvement was not superior to those without reinnervation.

Building Dual AI Models and Nomograms Using Noninvasive Parameters for Aiding Male Bladder Outlet Obstruction Diagnosis and Minimizing the Need for Invasive Video-Urodynamic Studies: Development and Validation Study.

BACKGROUND: Diagnosing underlying causes of nonneurogenic male lower urinary tract symptoms associated with bladder outlet obstruction (BOO) is challenging. Video-urodynamic studies (VUDS) and pressure-flow studies (PFS) are both invasive diagnostic methods for BOO. VUDS can more precisely differentiate etiologies of male BOO, such as benign prostatic obstruction, primary bladder neck obstruction, and dysfunctional voiding, potentially outperforming PFS. OBJECTIVE: These examinations' invasive nature highlights the need for developing noninvasive predictive models to facilitate BOO diagnosis and reduce the necessity for invasive procedures. METHODS: We conducted a retrospective study with a cohort of men with medication-refractory, nonneurogenic lower urinary tract symptoms suspected of BOO who underwent VUDS from 2001 to 2022. In total, 2 BOO predictive models were developed-1 based on the International Continence Society's definition (International Continence Society-defined bladder outlet obstruction; ICS-BOO) and the other on video-urodynamic studies-diagnosed bladder outlet obstruction (VBOO). The patient cohort was randomly split into training and test sets for analysis. A total of 6 machine learning algorithms, including logistic regression, were used for model development. During model development, we first performed development validation using repeated 5-fold cross-validation on the training set and then test validation to assess the model's performance on an independent test set. Both models were implemented as paper-based nomograms and integrated into a web-based artificial intelligence prediction tool to aid clinical decision-making. RESULTS: Among 307 patients, 26.7% (n=82) met the ICS-BOO criteria, while 82.1% (n=252) were diagnosed with VBOO. The ICS-BOO prediction model had a mean area under the receiver operating characteristic curve (AUC) of 0.74 (SD 0.09) and mean accuracy of 0.76 (SD 0.04) in development validation and AUC and accuracy of 0.86 and 0.77, respectively, in test validation. The VBOO prediction model yielded a mean AUC of 0.71 (SD 0.06) and mean accuracy of 0.77 (SD 0.06) internally, with AUC and accuracy of 0.72 and 0.76, respectively, externally. When both models' predictions are applied to the same patient, their combined insights can significantly enhance clinical decision-making and simplify the diagnostic pathway. By the dual-model prediction approach, if both models positively predict BOO, suggesting all cases actually resulted from medication-refractory primary bladder neck obstruction or benign prostatic obstruction, surgical intervention may be considered. Thus, VUDS might be unnecessary for 100 (32.6%) patients. Conversely, when ICS-BOO predictions are negative but VBOO predictions are positive, indicating varied etiology, VUDS rather than PFS is advised for precise diagnosis and guiding subsequent therapy, accurately identifying 51.1% (47/92) of patients for VUDS. CONCLUSIONS: The 2 machine learning models predicting ICS-BOO and VBOO, based on 6 noninvasive clinical parameters, demonstrate commendable discrimination performance. Using the dual-model prediction approach, when both models predict positively, VUDS may be avoided, assisting in male BOO diagnosis and reducing the need for such invasive procedures.

Lower urinary tract dysfunction in the central nervous system neurogenic bladder and the real-life treatment outcome of botulinum toxin A.

Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with central nervous system (CNS) lesions. Cases of cerebrovascular accidents (CVA), Parkinson's disease, dementia, and other intracranial lesions develop poor bladder control with or without urinary difficulty due to loss of cortical perception of bladder filling sensation and poor coordination of urethral sphincter relaxation during reflex micturition. Patients with CNS lesions usually have overactive bladder (OAB) symptoms, including urgency, frequency, incontinence, voiding symptoms of dysuria, large postvoid residual volume, and retention. In elderly patients with severe CNS disease the OAB symptoms are usually difficult to adequately relieve by medical treatment, and thus, their quality of life is greatly. Botulinum toxin A (BoNT-A) is currently licensed and has been applied in patients with idiopathic and neurogenic OAB due to spinal cord injury or multiple sclerosis. However, the application of BoNT-A in the treatment of urinary incontinence due to NLUTD in chronic CNS lesions has not been well-documented. Although cohort studies and case series support BoNT-A treatment for neurogenic OAB, chronic urine retention after intravesical BoNT-A injection for OAB and exacerbated urinary incontinence after urethral BoNT-A injection for voiding dysfunction have greatly limited its application among patients with NLUTD due to CNS lesions. This article reviews the pathophysiology and clinical characteristics of NLUTD in patients with CNS lesions and the clinical effects and adverse events of BoNT-A injection for patients with NLUTD. A flowchart was created to outline the patient selection and treatment strategy for neurogenic OAB.

Risk factors of video urodynamics and bladder management for long-term complications in patients with chronic spinal cord injury.

This study explores 15-year urological complications in chronic spinal cord injury (SCI) patients and investigates the predictive factors from video-urodynamic study (VUDS) and bladder management. Analyzing 864 SCI patients with a mean 15.6-year follow-up, we assessed complications and utilized multivariate logistic regression for risk evaluation. VUDS factors such as autonomic dysreflexia, detrusor sphincter dyssynergia, vesicourethral reflux (VUR), contracted bladder, and high voiding detrusor pressure significantly increased the likelihood of recurrent urinary tract infections (rUTI). Low bladder compliance, VUR, and contracted bladder notably raised the risk of hydronephrosis, while contracted bladder and detrusor overactivity with detrusor underactivity heightened chronic kidney disease risk. Volitional voiding reduced rUTI and VUR risk, whereas Valsalva maneuver-assisted voiding increased hydronephrosis risk. In conclusion, a contracted bladder identified in VUDS is associated with long-term urological complications in SCI, we propose that patients already experiencing a contracted bladder should prioritize volitional voiding as their preferred bladder management strategy to minimize the risk of additional complications such as rUTI and VUR. These findings unveil previously unexplored aspects in research, emphasizing the need for proactive management strategies in this patient population.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Effect of lower urinary tract conditions on surgical outcomes of different suburethral sling procedures for female stress urinary incontinence.

PURPOSE: The suburethral sling procedure has been widely used as the first-line treatment for female stress urinary incontinence (SUI). This study retrospectively compared the long-term surgical outcomes and complications between retropubic and transobturator suburethral sling procedures. METHODS: From 2010 to 2022, a total of 533 women with SUI underwent retropubic pubovaginal sling (PVS) or transobturator tape (TOT) procedures using a synthetic polypropylene mesh with or without concomitant anterior colporrhaphy. All patients underwent preoperative videourodynamic studies, Valsalva leak point pressure (VLPP), and voiding efficiency (VE). The success rate, postoperative complications, overactive bladder symptoms, transvaginal urethrolysis, and repeat procedures were compared among different surgical procedures. RESULTS: Among the patients, PVS was performed in 251 (47.1%) patients and with colporrhaphy in 58 (10.9%), TOT in 174 (32.6%) and with colporrhaphy in 50 (9.4%). The success rate was 87.4% in the PVS group and 75.4% in the TOT group, with or without colporrhaphy (p = 0.001). Urethrolysis was performed in 4.7% of the patients, and repeat suburethral sling procedures were performed in 8.3%. The overall success rate was significantly lower in TOT group, either with high or low VLPP, or with high or low VE. The rate of persistent OAB was significantly higher in TOT group regardless of VLPP or VE, whereas patients with VE < 90% at baseline had a significantly higher rate of postoperative dysuria. CONCLUSION: TOT procedures had an inferior long-term success rate than PVS procedures for female SUI. Additionally, no differences in the success rate were observed between patients with different bladder functions, high or low VLPP, and high or low VE.

Treatment Patterns with Mirabegron and Antimuscarinics for Overactive Bladder: A Prospective, Registry Study in Taiwan and South Korea (FAITH).

INTRODUCTION: This study aimed to assess overactive bladder (OAB) treatment patterns and factors associated with effectiveness and persistence. METHODS: A prospective, longitudinal, observational registry study of adults starting OAB therapy with mirabegron or antimuscarinics was undertaken. Primary endpoints were time from treatment initiation to discontinuation/switching; proportion who discontinued/switched; and reasons for discontinuation/switching. Secondary endpoints included OAB Symptom Score (OABSS), OAB Questionnaire: Short Form, and OAB Bladder Assessment Tool scores; factors associated with effectiveness and persistence; and safety. RESULTS: In total, 556 patients initiating mirabegron and 250 initiating antimuscarinics were enrolled. There was no treatment switch, change, or discontinuation in 68.5% of the mirabegron initiator group and median time to treatment change was not reached. Mean initial treatment duration was 130.8 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, and patients with mild and moderate OAB had significantly better persistence with mirabegron than those with severe OAB. Urinary tract infection was the most common adverse event with mirabegron. There was no treatment switch, change, or discontinuation in 60.4% of the antimuscarinics initiator group and median time to treatment change was not reached. Solifenacin was the most frequent initial treatment (66.0%). Mean treatment duration was 122.2 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, while patients with OAB medication in the 12 months before enrollment had significantly better persistence with antimuscarinics than those with no previous OAB medication. Dry mouth was the most common adverse event with antimuscarinics. CONCLUSIONS: Mirabegron and solifenacin were commonly prescribed as first-line OAB medications. There was no treatment switch, change, or discontinuation in more than 60% of the mirabegron initiator and antimuscarinics initiator groups. Mean initial treatment duration was 130.8 days and 122.2 days for mirabegron and antimuscarinics, respectively. Graphical Abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov NCT03572231.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. METHODS: The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. RESULTS: Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. CONCLUSION: Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

Real-Life Treatment Outcome of Botulinum Toxin A Injection on Overactive Bladder and Voiding Dysfunction in Patients with Central Nervous System Lesions.

PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with neurological lesions in the central nervous system (CNS). Medical treatment usually cannot adequately relieve NLUTD. This study reported the real-life treatment outcome of botulinum toxin A (BoNT-A) for overactive bladders (OAB) and voiding dysfunction in patients with CNS lesions. METHODS: We retrospectively analyzed the first-time treatment outcome of 74 patients who received detrusor 100 U BoNT-A for OAB and 45 patients who received a urethral sphincter 100 U BoNT-A injection for voiding dysfunction. The treatment outcome, therapeutic duration, and adverse events (AE) after BoNT-A were compared among different CNS lesions and among patients with different urodynamic characteristics. RESULTS: The study included 74 patients receiving detrusor injections for OAB (36 with cerebrovascular accidents, 13 with Parkinson's disease, and 25 with dementia) and 45 patients receiving a urethral sphincter injection for voiding dysfunction (26 with cerebrovascular accidents, 7 with Parkinson's disease, and 12 with dementia). After detrusor BoNT-A treatment, urinary continence was achieved in 28.4% of patients with neurogenic OAB, postoperative difficult urination in 59.5%, acute urinary retention (AUR) in 9.5%, and urinary tract infection (UTI) in 14.9%, with a therapeutic duration of 6.43 months. There were no differences among subgroups or between patients with detrusor overactivity (DO) and DO with detrusor underactivity (DU) in terms of treatment outcomes and AEs. The improvement rate of urethral sphincter BoNT-A injections was 75.6% without any difference among subgroups. After treatment, 24.4% of the patients had exacerbated urinary incontinence, 33.3% had persistent difficult urination, and 15.6% had UTI. Patients with dementia had higher rates of difficult urination and UTI, higher postvoid residual volume, and a shorter therapeutic duration. Patients with DU and those without urethral sphincter dyssynergia had less favorable outcomes after their urethral sphincter BoNT-A injection. CONCLUSIONS: The therapeutic efficacy of detrusor BoNT-A injection for OAB due to CNS lesions is limited, with high rates of difficult urination, AUR, and UTI. Although urethral sphincter BoNT-A injection is effective in treating voiding dysfunction; however, exacerbated urinary incontinence and persistent difficult urination remain a problem, particularly in patients with dementia.

Urinary Viral Spectrum in Patients with Interstitial Cystitis/Bladder Pain Syndrome and the Clinical Efficacy of Valacyclovir Treatment.

Our previous study showed that the Epstein-Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. Twenty-eight patients were prospectively enrolled for valacyclovir 500 mg twice a day for 4 weeks. Urine samples were collected from IC/BPS patients and 30 controls. The primary outcome was the difference in the visual analog scale (VAS) pain score, and secondary outcomes included changes in the urinary viral spectrum and urinary inflammatory cytokine level (ClinicalTrials.gov Identifier: NCT05094414). Urinary EBV was detected in 14.2% IC/BPS patients but not in the controls. Urinary John Cunningham virus and BK virus were detected in 18 (64.3%) and 2 (7.1%) patients with IC/BPS, respectively, with similar prevalences noted for the controls. No cytomegalovirus, varicella-zoster virus, or herpes simplex virus was detected in the urine samples. The VAS pain score in patients with IC/BPS significantly decreased after 4 weeks (from 7.5 [5.52-9.0] to 5 [1.5-6.0], p = 0.0003). Urinary EBV was undetectable in any sample after valacyclovir treatment, and the decreases in urinary interleukin (IL)-1ß (from 0.66 [0.55-0.82] pg/mL to 0.58 [0.55-0.64] pg/mL, p = 0.0034), IL-8 (from 6.81 [2.38 to 29.1] pg/mL to 4.33 [1.53-11.04] pg/mL, p = 0.0361), IL-10 (from 1.06 [0.94-1.18] pg/mL to 0.92 [0.88-1.02], p = 0.0086), and tumor necrosis factor-α (from 1.61 [1.50-1.72] pg/mL to 1.50 [1.44-1.55] pg/mL, p = 0.0079) were significant. Valacyclovir could relieve bladder pain, eliminate urinary EBV, and reduce bladder inflammation.

Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Cystoscopic characteristic findings of interstitial cystitis and clinical implications.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease of unknown etiology, characterized by bladder pain and frequency urgency symptoms. Based on the cystoscopic findings after hydrodistention under anesthesia, the phenotype of IC/BPS includes no glamerulation, characteristic glomerulation, and with Hunner's lesion. IC is specifically defined if there are characteristic Hunner's lesion appeared in cystoscopy or after hydrodistention. If there are glomerulations without Hunner's lesion, BPS should be considered. The definition of Hunner's lesion and glomerulations differs based on different definition and observations. Currently, there has been no clear description and grading of the glomerulations and Hunner's lesion. Because the classification of IC/BPS has an impact on the treatment strategy and associated with therapeutic outcome, it is unmet to have a clear definition and consensus on the characteristic cystoscopic findings of IC/BPS. This article reviews the literature and presents the figures of Hunner's lesions and description of different mucosal lesions after cystoscopic hydrodistention.

Intravesical Botulinum Toxin Injection Plus Hydrodistention Is More Effective in Patients with Bladder Pain-Predominant Interstitial Cystitis/Bladder Pain Syndrome.

Intravesical botulinum toxin A (BoNT-A) injections are included in the interstitial cystitis/bladder pain syndrome (IC/BPS) treatment guidelines. However, the IC phenotype suitable for treatment with BoNT-A has not been clarified. Therefore, we identified the factors influencing treatment outcomes for intravesical BoNT-A injections in patients with non-Hunner IC/BPS (NHIC). This retrospective study included patients with NHIC who underwent 100 U BoNT-A intravesical injections over the past two decades. Six months after treatment, treatment outcomes were assessed using the Global Response Assessment (GRA). Outcome endpoints included GRA, clinical symptoms, urodynamic parameters, urine biomarkers, and the identification of factors contributing to satisfactory treatment outcomes. The study included 220 patients with NHIC (42 men, 178 women). The satisfactory group (n = 96, 44%) had significantly higher pain severity scores and IC symptoms index, larger maximum bladder capacity (MBC), and lower 8-isoprostane levels at baseline. Logistic regression revealed that larger MBC (≥760 mL) and bladder pain predominance were associated with satisfactory outcomes after BoNT-A injection. Subjective parameters and pain severity scores improved significantly in patients with bladder pain-predominant IC/BPS after BoNT-A injection. Thus, NHIC patients with bladder or pelvic pain are more likely to experience satisfactory outcomes following intravesical BoNT-A injections.

Multimodal therapies and strategies for the treatment of interstitial cystitis/bladder pain syndrome in Taiwan.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by bladder pain, frequency, and nocturia. The most common pathologies include chronic inflammation and bladder urothelium dysfunction. According to the bladder condition with or without Hunner's lesions, IC/BPS can be divided into "IC" in patients with Hunner's lesion (HIC) and "BPS" in those without Hunner's lesion (NHIC). Previous studies have reported greater central sensitization and interorgan cross-talk in patients with NHIC. Multimodal treatments have been recommended in clinical guidelines under the biopsychosocial model. The bladder-gut-brain axis has also been speculated, and multimodal therapies are necessary. Unfortunately, currently, no treatment has been reported durable for IC/BPS. Patients with IC/BPS usually experience anxiety, depression, holistic physical responses, and even threats to social support systems. The lack of durable treatment outcomes might result from inadequate diagnostic accuracy and differentiation of clinical phenotypes based on the underlying pathophysiology. Precision assessment and treatment are essential for optimal therapy under definite IC/BPS phenotype. This article reviewed currently available literature and proposed a diagnosis and treatment algorithm. Based on bladder therapy combined with suitable physical and psychological therapies, a well-grounded multimodal therapy and treatment algorithm for IC/BPS following a diagnostic protocol are indispensable.

Management of spinal cord injury patients with neurogenic lower urinary tract dysfunction using minimally invasive and surgical therapies in Taiwan.

The main problems of neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury (SCI) consist of impaired urine storage, impaired bladder emptying, or both. The priorities in the management of SCI-NLUTD should be preservation of renal function, followed by freedom from urinary tract infections and improvement of quality of life. Management of NLUTD in patients with SCI must be based on urodynamic findings rather than clinical evaluations. In the hospital without urodynamic equipment, careful measurement of intravesical pressure and safety functional bladder capacity in conjunction with clinical assessment are also feasible. Identification of high-risk patients is important for preventing urological complications in patients with chronic SCI. The management of NLUTD should start with conservative bladder management and medical treatment. Patients with SCI should be regularly followed up, and any NLUTDs and urological complications should be adequately treated. When surgical intervention is necessary, less invasive and reversible procedures should be considered first, and any unnecessary surgery should be avoided. This article reports the current evidence and expert opinions on the patient-centered bladder management of NLUTD in chronic SCI patients in Taiwan. To avoid renal function deterioration and urological complications, annual active surveillance of bladder and renal function is mandatory, especially for high-risk SCI patients.