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.

EBV infection mediated BDNF expression is associated with bladder inflammation in interstitial cystitis/bladder pain syndrome with Hunner's lesion.

Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both Epstein-Barr virus (EBV) latency infection genes EBNA-1 and LMP-1 and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating the coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and upregulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF to be EBV-infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. A chromatin immunoprecipitation study revealed BDNF transcription could be promoted by cooperation between EBV nuclear antigens, chromatin modifiers, and B-cell-specific transcription. Knockdown of BDNF in EBV-infected B cells resulted in the inhibition of cell proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV-infected B cells into rat bladder walls resulted in a higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV-infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV-infected B cells in HIC pathogenesis. © 2022 The Pathological Society of Great Britain and Ireland.

Efficacy of single and repeated transurethral bladder neck incisions for female voiding dysfunction.

OBJECTIVE: This study aimed to assess the efficacy of single and repeat transurethral bladder neck incision (TUI-BN) for female voiding dysfunction caused by bladder outlet obstruction (BNO). Further, the predictive factors associated with better treatment outcomes were identified. METHODS: Women with voiding difficulty due to BNO who underwent TUI-BN were included in this research. All patients underwent videourodynamics study at baseline and after TUI-BN. Successful outcome was defined as a voiding efficiency of ≥ 66.7% and a global response assessment score of ≥ 2 after treatment. Repeat TUI-BN was considered for patients with insufficient improvement. The outcomes of repeat surgery, surgical complications, and predictive factors of successful outcomes were evaluated. RESULTS: In total 158 cases, the success rates were 61.4% and 45.2% after the first and second TUI-BN, respectively, with an overall cumulative rate of 70.3%. The success rates were comparable between patients with detrusor underactivity (DU) and those without (54.9% vs. 68.4%). The absence of a previous history of suburethral sling and a high baseline corrected maximum flow rate were a significant predictor of favorable outcomes. The cumulative rate of regaining self-voiding function was 95.1%. The incidence rates of vesico-vaginal fistula and de novo stress urinary incontinence requiring surgery were 1.2% and 2.5%, respectively. CONCLUSIONS: Regardless of the presence of DU, TUI-BN is effective against female voiding dysfunction caused by BNO. Repeat procedures are beneficial and can improve self-voiding function. A high corrected maximum flow rate and the absence of a previous history of suburethral sling can contribute to greater success rates.

Bladder neck incompetence could be an etiology of overactive bladder syndrome in women with stress urinary incontinence after anti-incontinence surgery: insights from transrectal sonography.

PURPOSE: To investigate the prevalence of bladder neck incompetence (BNI) and the anatomic differences between different types of urinary incontinence (UI) and overactive bladder (OAB) by transrectal sonography, and to investigate these differences among those with stress UI (SUI) or mixed UI (MUI) who exhibited de novo or persistent OAB symptoms following anti-incontinence surgery. METHODS: A retrospective analysis was conducted on a total of 184 patients with SUI, MUI, urge UI (UUI), or OAB dry who underwent transrectal ultrasound between 2017 and 2022. The presence of BNI and urethral incompetence assessed by transrectal ultrasound were recorded in all included patients, and recorded preoperatively and postoperatively among patients with SUI and MUI who underwent anti-incontinence surgery. RESULTS: Among the patients, 91%, 84%, 76%, and 71% exhibited BNI in MUI, SUI, UUI, OAB dry group, respectively. Significantly higher rate of patients with BNI were found in MUI than in OAB dry group. Patients with OAB symptoms after anti-incontinence surgery exhibited significantly higher rates of BNI and urethral incompetence than those who did not have postoperative OAB symptoms. Among MUI patients with preoperative BNI, significantly lower rate of postoperative BNI and urethral incompetence was observed in individuals who had improved OAB symptoms after surgery, compared to those without improvement. CONCLUSION: A higher BNI rate was observed in the MUI group. A significantly higher BNI rate was observed in women with OAB symptoms after anti-incontinence surgery. Patients with MUI had improved OAB symptoms if BNI was successfully corrected after anti-incontinence surgery.

Sensory Receptor, Inflammatory, and Apoptotic Protein Expression in the Bladder Urothelium of Patients with Different Subtypes of Interstitial Cystitis/Bladder Pain Syndrome.

The aim of this study was to investigate the expression levels of sensory receptors, inflammatory proteins, and pro-apoptotic proteins in the urothelium of non-Hunner's interstitial cystitis (NHIC) bladders of patients with different clinical and cystoscopic phenotypes. The urothelia from the bladders of 52 NHIC patients were harvested. The expression of sensory receptors, including TRPV1, TRPV4, TRPA1, H1-receptors, and sigma-1 receptors; the inflammatory proteins p38 and tryptase; and the pro-apoptotic proteins, such as caspase-3, BAD, and BAX in the urothelium, were investigated using immunohistochemistry and Western blotting. We compared the expression levels of these proteins in NHIC subtypes according to IC symptom scores, visual analog scores of bladder pain, maximal bladder capacity, glomerulation grades, and combined maximal bladder capacity and glomerulations after cystoscopic hydrodistention. The expression levels of TRPV1, TRPV4, sigma-1, P38, tryptase, caspase-3, and BAD were significantly increased in the urothelium of IC/BPS patients compared with the expression levels in the controls. TRPV1 was significantly associated with IC symptom severity. However, no significant differences in sensory receptor expression in the IC/BPS bladders with different bladder conditions were detected. Inflammatory and pro-apoptotic protein expression levels in the urothelium were similar among the IC/BPS subgroups. This study concluded that IC/BPS patients with frequency and bladder pain complaints have higher levels of urothelial sensory receptors, and inflammatory and pro-apoptotic proteins. The expression levels of these sensory receptors, inflammatory proteins, and pro-apoptotic proteins are not significantly different among IC/BPS bladders with different conditions.

Use of Urinary Biomarkers in Discriminating Interstitial Cystitis/Bladder Pain Syndrome from Male Lower Urinary Tract Dysfunctions.

To analyze the urinary biomarkers in men with lower urinary-tract symptoms (LUTS) and identify interstitial cystitis/bladder pain syndrome (IC/BPS) from the other lower urinary-tract dysfunctions (LUTDs) by the levels of characteristic urinary biomarkers. In total, 198 men with LUTS were prospectively enrolled and urine samples were collected before intervention or medical treatment. Videourodynamic studies were routinely performed and the LUTDs were diagnosed as having bladder-outlet obstruction (BOO) such as bladder-neck dysfunction, benign prostatic obstruction, or poor relaxation of external sphincter (PRES); and bladder dysfunction such as detrusor overactivity (DO), hypersensitive bladder (HSB), and IC/BPS. Patients suspicious of IC/BPS were further confirmed by cystoscopic hydrodistention under anesthesia. The urine samples were investigated for 11 urinary inflammatory biomarkers including eotaxin, IL-6, IL-8, CXCL10, MCP-1, MIP-1ß, RANTES, TNF-α, NGF, BDNF, and PGE2; and 3 oxidative stress biomarkers 8-OHdG, 8-isoprostane, and TAC. The urinary biomarker levels were analyzed between LUTD subgroups and IC/BPS patients. The results of this study revealed that among the patients, IC/BPS was diagnosed in 48, BOO in 66, DO in 25, HSB in 27, PRES in 15, and normal in 17. Patients with BOO had a higher detrusor pressure and BOO index than IC/BPS, whereas patients with IC/BPS, BOO, and DO had a smaller cystometric bladder capacity than the PRES and normal subgroups. Among the urinary biomarkers, patients with IC/BPS had significantly higher levels of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC than all other LUTD subgroups. By a combination of different characteristic urinary biomarkers, TNF-α, and eotaxin, either alone or in combination, had the highest sensitivity, specificity, positive predictive value, and negative predictive value to discriminate IC/BPS from patients of all other LUTD subgroups, BOO, DO, or HSB subgroups. Inflammatory biomarker MCP-1 and oxidative stress biomarkers 8-OHdG and TAC, although significantly higher in IC/BPS than normal and PRES subgroups, did not have a diagnostic value between male patients with IC/BPS and the BOO, DO, or HSB subgroups. The study concluded that using urinary TNF-α and eotaxin levels, either alone or in combination, can be used as biomarkers to discriminate patients with IC/BPS from the other LUTD subgroups in men with LUTS.

The Tumor Necrosis Factor-α Level in Platelet-Rich Plasma Might Be Associated with Treatment Outcome in Patients with Interstitial Cystitis/Bladder Pain Syndrome or Recurrent Urinary Tract Infection.

Using platelet-rich plasma (PRP) injections to treat urological diseases has attracted great attention. This study investigated the impact of cytokine concentrations in PRP on the treatment outcome of patients with recurrent urinary tract infection (rUTI) and interstitial cystitis/bladder pain syndrome (IC/BPS). Forty patients with IC/BPS and twenty-one patients with rUTI were enrolled for four-monthly repeated PRP injections. PRP was collected at the first injection and analyzed with multiplex immunoassays for 12 target cytokines. In patients with IC/BPS, a Global Response Assessment (GRA) score ≥ 2 was defined as a successful outcome. In rUTI patients, ≤2 episodes of UTI recurrence during one year of follow-up was considered a successful outcome. Nineteen (47.5%) patients with IC/BPS and eleven (52.4%) patients with rUTI had successful outcomes. The IC/BPS patients with successful outcomes had significantly lower levels of tumor necrosis factor-α (TNF-α) in their PRP than those with unsuccessful outcomes (p = 0.041). The rUTI patients with successful outcomes also had a lower level of TNF-α (p = 0.025) and a higher level of epidermal growth factor (p = 0.035) and transforming growth factor-ß2 (p = 0.024) in PRP than those with unsuccessful outcomes. A lower level of TNF-α in PRP might be a potentially predictive factor of treatment outcome.

Video-urodynamic characteristics of lower urinary tract dysfunctions in patients with chronic brain disorders.

AIMS: Lower urinary tract dysfunction (LUTD) is common in patients with chronic brain disorders. This study investigated the video-urodynamic study (VUDS) findings of LUTD in patients with chronic brain disorders, including cerebrovascular accident (CVA), Parkinson's disease (PD), and early dementia. METHODS: A total of 169 patients with a history of chronic brain disorders, including 84 with CVA, 55 with PD, and 30 with early dementia were enrolled. All patients had a comprehensive chart review, including brain disorder subtype, the period from diagnosis to VUDS, the VUDS parameters, and final LUTD. RESULTS: The mean age of patients was 69.2 ± 10.5 years, and the interval from brain insult to VUDS was 61.3 ± 49.7 months. Urodynamic detrusor overactivity (DO) was noted in 73.4% of patients, detrusor underactivity in 10.1%, and detrusor overactivity with detrusor underactivity in 16.6%. Bladder outlet obstruction (BOO) was noted in 60.9% of patients, including bladder neck dysfunction in 21.3%, urethral sphincter dysfunction in 42%, and prostatic obstruction in 10.1% of male patients. Urethral sphincter dysfunction was noted in 60% of patients with PD, 32.1% with CVA, and 36.7% with dementia (p = 0.004). A low mean maximum flow rate increased post-void residual volume, and poor voiding efficiency was common in these patients, without significant differences among the subgroups. CONCLUSIONS: Real-world VUDSs revealed that patients with chronic brain disorders not only had a high prevalence of DO but also impaired bladder contractility and a high rate of BOO at the level above the bladder neck and urethral sphincter.

Effect of videourodynamic subtypes on treatment outcomes of female dysfunctional voiding.

INTRODUCTION AND HYPOTHESIS: Dysfunctional voiding (DV) is not uncommon in women and is typically challenging to treat. This study retrospectively investigated the long-term treatment outcomes of DV women with different videourodynamics (VUDS) characteristics. METHODS: Data of women with VUDS-proven DV (n = 302) were retrospectively analyzed. All patients at first received biofeedback pelvic floor muscle training and medications; urethral sphincter botulinum toxin A injection was administered after treatment failure. Long-term follow-up outcomes were graded by global response assessment (GRA) and objective responses of decrease of detrusor pressure (Pdet), increase in maximum flow rate (Qmax) and voiding efficiency (VE). The treatment outcomes were investigated among different VUDS subgroups. RESULTS: Of 302 women, 165 (54.6%) had mid-urethral DV, 117 (38.7%) had distal urethral DV, and 20 (6.6%) had both bladder neck dysfunction (BND) and mid-urethral DV. A total of 170 (56.3%) patients were available for follow-up VUDS after treatment. Pdet was decreased in all three subgroups, but increase in Qmax and VE was only noted in the BND plus DV subgroup. Overall, 120 (70.6%) patients showed improvement (GRA ≥ 1), including 14 with BND plus DV (93.3%), 50 with mid-urethral DV (60.8%) and 56 with distal urethral DV (77.8%) (p = 0.044). All three subgroups showed significant reduction in bladder outlet obstruction index after treatment, with BND plus DV subgroup showing the greatest reduction. CONCLUSIONS: Women with DV have different VUDS characteristics resulting from different pathophysiological mechanisms and treatment results. The VUDS characteristics may help predict treatment outcomes of female DV.

Therapeutic efficacy and cognitive adverse events of overactive bladder medication in patients with central nervous system Disorders-A cohort study.

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner's lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1ß), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner's IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1ß, and RANTES levels than those with non-Hunner's IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1ß, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

Clinical Relevance of Bladder Histopathological Findings and Their Impact on Treatment Outcomes among Patients with Interstitial Cystitis/Bladder Pain Syndrome: An Investigation of the European Society for the Study of Interstitial Cystitis Histopathological Classification.

PURPOSE: We investigate the clinical significance of European Society for the Study of Interstitial Cystitis (ESSIC) bladder histopathological classification and its impact on treatment outcomes among patients with interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: Bladder biopsy specimens obtained from severe, treatment refractory interstitial cystitis/bladder pain syndrome cases were analyzed by a single pathologist blinded to clinical data. Inflammatory cell infiltration and urothelium denudation, eosinophil infiltration, plasma cell infiltration, lamina propria hemorrhage and granulation in specimens were evaluated separately. Patients with at least 1 histopathological finding were classified as ESSIC type C, with the rest being classified as ESSIC type A. Current overall treatment outcomes were determined via telephone interview. RESULTS: Bladder specimens were obtained from 352 patients with interstitial cystitis/bladder pain syndrome. Bladder inflammation, urothelium denudation, eosinophil and plasma cell infiltration, lamina propria hemorrhage and granulation were present in 69.6%, 44.6%, 9.1%, 15.3%, 4.8% and 5.1% of the bladder specimens, respectively. Approximately 78.7% of the patients included were ESSIC type C and had a smaller cystometric bladder capacity and higher bladder pain compared to ESSIC type A. Although individual histopathological findings were not associated with treatment outcome, a higher proportion of ESSIC type A patients had worse, unchanged or less than 25% improvement outcomes compared to ESSIC type C (43.1% vs 25.8%, p=0.025). CONCLUSIONS: Bladder histopathological findings were associated with clinical parameters and differences in patient reported treatment outcomes. Accordingly, patients with interstitial cystitis/bladder pain syndrome who had no remarkable bladder histopathological findings had less favorable treatment outcomes compared to those who did.

High percentage of neurologic deficits in the electrophysiology study of the lower urinary tract in patients with detrusor underactivity and chronic urinary retention.

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.

Will detrusor acontractility recover after medical or surgical treatment? A longitudinal long-term urodynamic follow-up.

AIMS: Patients with urinary retention due to detrusor acontractility (DA) might regain voiding efficiency (VE) after treatment. This study investigated the long-term outcomes and predictors of recovery following treatment. METHODS: A total of 32 patients with DA were retrospectively identified and enrolled. DA was defined by Pdet .Qmax = 0 cmH2 O and postvoid residual (PVR) > 300 ml determined through videourodynamic study (VUDS). All patients received medical or surgical treatment and were followed up for at least 3 months, during which repeat VUDS was conducted. Detrusor contractility recovery was confirmed when patients were able to void with a Pdet .Qmax ≥ 10 cmH2 O after treatment. RESULTS: Our patients comprised 22 women and 10 men (mean age, 73.2 ± 9.7 years; mean follow-up duration, 1.6 ± 1.8 [0.3-7.4] years). Follow-up VUDS revealed that 14 (43.9%) patients recovered from detrusor contractility, with five patients recovering within 1 year and nine after 1 year. Pdet .Qmax , voided volume, PVR, maximum flow rate, and VE significantly improved in both the recovery and nonrecovery groups. The recovery group had significantly better VE (p = .039) and significantly lower bladder compliance (74.2 ± 83.2 vs. 119 ± 82.6; p = .007) than the nonrecovery group. Receiver operating characteristic (ROC) analysis revealed an optimum bladder compliance cutoff value of <80 ml/cmH2 O for predicting detrusor contractility recovery with an area under the ROC curve of 0.780. CONCLUSIONS: Among the included patients with DA, 43.9% had detrusor contractility recovery after treatment, with bladder compliance of <80 ml/cmH2 O predicting bladder function recovery.

Voiding dysfunctions in patients with non-Hunner's ulcer interstitial cystitis/bladder pain syndrome do not affect long-term treatment outcome.

PURPOSE: The role of urodynamic study in the diagnosis and prognostication of interstitial cystitis/bladder pain syndrome (IC/BPS) is still controversial. This study evaluated the correlation of the baseline voiding dysfunctions and long-term treatment outcome in patients with non-Hunner's ulcer IC (NHIC). MATERIALS AND METHODS: A total of 211 NHIC patients were enrolled. All patients underwent videourodynamic (VUDS) examination at baseline to identify their voiding conditions and received subsequent treatments. The primary endpoint was Global Response Assessment (GRA) at the interview. Secondary endpoints included O'Leary-Sant symptom score (OSS), Visual Analogue Scale (VAS) for pain and the rate of IC symptom flare-up. RESULTS: The mean age was 56.8 ± 12.8 years, and mean duration of IC was 16.0 ± 9.9 years. At baseline, 83 (39.3%) patients had a voiding dysfunction and 132 (62.7%) had 1 to 3 co-morbidities. The duration, co-morbidities, treatments, changes in OSS and VAS, maximum bladder capacity (MBC), glomerulations, GRA and flare-up rate showed no significant difference among different subgroups. When we divided patients by their storage and voiding conditions, patients with non-hypersensitivity bladder (HSB) (n = 32) had significantly greater MBC (P = .002) whereas those with HSB with (n = 76) or without (n = 103) voiding dysfunction had higher glomerulation (P = .021). When we analysed voiding dysfunction subgroups by GRA, patients with a GRA of ≥2 had a significantly shorter duration of disease (13.9 ± 8.6 years, P = .021). There were also significant associations between GRA and the changes of OSS (P < .001) and VAS (P < .001). CONCLUSIONS: VUDS can disclose voiding dysfunction in 39.3% of NHIC patients. With adequate therapy, the voiding dysfunctions in NHIC patients do not affect long-term treatment outcome.

Decreased urothelial cytoskeleton and cell proliferation protein expression suggest interstitial cystitis/bladder pain syndrome patients with Hunner's lesion and grade 3 glomerulation might be different from other types of patients.

OBJECTIVES: To explore the expression of cytoskeletal and cell proliferation proteins in urothelial cells of patients diagnosed with various clinical subtypes of interstitial cystitis/bladder pain syndrome. METHODS: Biopsy specimens from 85 interstitial cystitis/bladder pain syndrome patients were classified according to findings on cystoscopy. Cytokeratins and cell proliferation proteins detected in the specimens were evaluated with immunofluorescence staining and quantified with western blotting. A total of 22 patients diagnosed with pure stress urinary incontinence were enrolled as controls. RESULTS: Interstitial cystitis/bladder pain syndrome patients with Hunner's lesion and with grade 3 glomerulation hemorrhage had smaller bladder capacities than the other interstitial cystitis/bladder pain syndrome patients without Hunner's lesion. Diminished expression of CK14, CK20, cell proliferation protein tumor protein 63, sonic hedgehog, and fibroblast growth factor receptors 3 and 4, and increased expression of CK5 and BCL2-associated X protein were observed in biopsy specimens from patients with Hunner's lesion compared with those from patients without Hunner's lesion and controls. In the patients with grade 3 glomerulation hemorrhage, lower expression levels of urothelial CK20, tumor protein 63 and fibroblast growth factor receptor 4, and lower expression of CK5 and BCL2-associated X protein were detected compared with other types of NHIC. CONCLUSION: A diminished expression of proliferation proteins tumor protein 63 and the mature urothelium marker CK20, and increased expression of the immature marker CK5 in specimens from both Hunner's lesion and grade 3 glomerulation hemorrhage patients can be observed. The urothelium of patients with interstitial cystitis/bladder pain syndrome might be in a state of persistent or chronic injury that could relate to the limited expression of cell proliferation proteins.

Predictors of further anti-incontinence interventions or transvaginal urethrolysis after a pubovaginal sling procedure in women with and without neurologic disorders.

BACKGROUND/PURPOSE: The impact of neurologic disorders on the clinical outcome of suburethral sling procedures has seldom been studied. Our aim is to elucidate factors predicting further anti-incontinence interventions or transvaginal urethrolysis after a re-adjustable pubovaginal sling procedure (PVS), especially in patients with neurologic disorders. METHODS: Medical records of all consecutive women who underwent re-adjustable PVS for stress urinary incontinence (SUI) were reviewed. RESULTS: A total of 589 women were enrolled, 152 (25.8%) women were found to have persistent or recurrent SUI after surgery, and 39 (6.6%) women underwent further anti-incontinence interventions. Postoperative voiding dysfunction was found in 46 (7.8%) women, and 23 women (3.9%) underwent transvaginal urethrolysis. Low body mass index (hazard ratio = 0.92) and low functional bladder capacity (dL, hazard ratio = 0.83) were factors predicting the presence of persistent/recurrent SUI. However, the presence of spinal cord disorder (hazard ratio = 8.91) and a history of prior surgery for pelvic organ prolapse (hazard ratio = 2.51) were factors predicting further anti-incontinence interventions. A high post-void residual volume (PVR, dL, hazard ratio = 1.52) and preoperative bladder outlet obstruction (BOO, hazard ratio = 5.39) were factors predicting postoperative voiding dysfunction. Similarly, a high PVR (dL, hazard ratio = 1.50) and preoperative BOO (hazard ratio = 5.38) were factors predicting transvaginal urethrolysis. A PVR >1.51 dL was an optimal cut-off value for predicting transvaginal urethrolysis. CONCLUSION: The presence of spinal cord disorder and prior surgery for pelvic organ prolapse were predictors of further anti-incontinence interventions after re-adjustable PVS. In addition, a large PVR and preoperative BOO were predictors of transvaginal urethrolysis after re-adjustable PVS.

Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1ß, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.

Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome-A prospective, multicenter, randomized, double-blind, placebo-controlled study.

AIMS: Extracorporeal shock wave therapy (ESWT) inhibited bladder inflammation and pain in preclinical studies. We assessed ESWT for the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This double-blind, randomized, placebo-controlled physician-initiated study enrolled 54 patients with IC/BPS. The patients were assigned to ESWT (N = 24; 2000 shocks, frequency of 3 Hz, and maximum total energy flow density 0.25 mJ/mm2 ) once a week for 4 weeks at suprapubic bladder area or placebo (N = 25; shock wave setting without energy transmission). The primary endpoint was the average changes in O'Leary-Sant symptom scores (OSS) between baseline and 4 weeks after treatment. Secondary endpoints included visual analog scale (VAS, 0-10) for pain, the average changes of variables in a 3-day voiding diary, and global response assessment of patient satisfaction. RESULTS: At 4 weeks posttreatment, both groups were associated with a statistically significant decrease in OSS and VAS pain scale. However, there were no difference in mean change between ESWT vs placebo groups. A significantly higher proportion of patients on ESWT responded as improved in the VAS ≥ 3 vs placebo (P = .035). At 12 weeks posttreatment, improvement in the VAS ≥ 3 was 57.1% vs 19.0% (ESWT vs placebo; P = .011). The finding was associated with an improvement in frequency - 1.0 ± 2.3 vs 0.7 ± 3.2 (ESWT vs placebo; P = .065). No significant adverse events were found in either group. CONCLUSIONS: A reduction in pain was discovered in this trial assessing ESWT in patients with IC/BPS but OSS, which was the primary outcome parameter, was not improved.

Obstructive patterns in videourodynamic studies predict responses of female dysfunctional voiding treated with or without urethral botulinum toxin injection: a long-term follow-up study.

INTRODUCTION AND HYPOTHESIS: We report long-term changes in VUDS profiles of women with dysfunctional voiding and investigate potential predictors for treatment response. METHODS: Women with dysfunctional voiding and available VUDS data between November 1997 and June 2018 were enrolled for retrospective analysis. The patients were all treated with medication first. In refractory patients, urethral botulinum toxin was provided as an additional option. The primary outcome was the change of VUDS parameters between baseline and follow-up studies. The secondary outcomes were baseline parameters and clinical factors that were associated with the BOOI response (> 10 points of BOOI reduction). RESULTS: A total of 195 women with DV were included in this study. The mean age was 54.5 years old. Sixty patients received urethral botulinum toxin injection. For all patients, Pdet decreased from 47.2 to 36.8 cm H2O (p < 0.0001), and BOOI decreased from 26.4 to 17.7 (p = 0.0001). Patients with urethral injection had significantly smaller Qmax, voided volume, and voiding efficiency (VE) and significantly larger PVR and BOOI at baseline, indicating a severer obstruction in this group. The overall BOOI response rate was 44% (85/195). A higher baseline BOOI was associated with the BOOI response in multivariate analysis. CONCLUSIONS: In this long-term study of women with dysfunctional voiding, medical treatment with or without urethral botulinum toxin injection both resulted in reduction of Pdet and BOOI. A more prominent obstructive profile at baseline VUDS study was associated with a higher rate of BOOI response at follow-up study.