The surgical effect on overactive bladder symptoms in women with pelvic organ prolapse.

This study aimed to explore the effect of pelvic reconstruction surgery on the relation of pelvic organ prolapse (POP) and overactive bladder (OAB) and the impact of preoperative vaginal oestrogen supplement on vaginal tissue. A total of 100 postmenopausal women with symptomatic POP who underwent pelvic reconstruction surgery (laparoscopic sacrocolpopexy or transvaginal mesh) were enrolled in this study. Preoperative vaginal oestrogen was prescribed in 28 cases. The evaluation tools consisted of POP-Q, urodynamic study, Overactive Bladder Symptom Score (OABSS), and urinary NGF. Vaginal maturation index and vaginal specimens for hormone receptors study were investigated during operation to evaluate the effect of topical oestrogen. Follow-up assessments were performed at 1, 3, and 6 months after surgery. Preoperatively, 58 (58%) were POP with OAB. After reconstruction surgery, the OABSS decreased significantly (6.87 ± 0.85 vs 3.77 ± 0.61, p < 0.001) at postoperative 6 months in the group. Remarkable increasing trends of urinary NGF levels are noted till 3 months postoperatively, then decreasing to the baseline level at 6 months postoperative follow-up. Remarkable decrease of mRNA of the androgen receptor and significant higher expression of progesterone receptor (PR) were noted after use of the vaginal oestrogen cream. The severity of OAB in the POP women shows moderate degree according to OABSS. Pelvic reconstruction surgery can significantly improve the OAB symptoms. The surgery induced inflammation effect lasts for about 6 months. Short-term preoperative supplement of topical oestrogen brings alterations of the vaginal epithelium.

Is coronavirus disease 2019 associated with indicators of long-term bladder dysfunction?

OBJECTIVE: Early reports have suggested that coronavirus disease 2019 (COVID-19) can present with significant urinary frequency and nocturia, and that these symptoms correlate with markers of inflammation in the urine. We evaluated surrogate markers of chronic urinary symptoms to determine if they were more frequent after COVID-19 infection. METHODS: Routinely collected data from the province of Ontario was used to conduct a matched, retrospective cohort study. We identified patients 66 years of age or older who had a positive COVID-19 test between February and May 2020 and survived at least 2 months after their diagnosis. We matched them to two similar patients who did not have a positive COVID-19 test during the same time period. We measured the frequency of urology consultation, cystoscopy, and new prescriptions for overactive bladder medications during a subsequent 3-month period. Proportional hazard models were adjusted for any baseline differences between the groups. RESULTS: We matched 5617 patients with COVID-19 to 11,225 people who did not have COVID-19. The groups were similar, aside from a higher proportion of patients having hypertension and diabetes in the CoVID-19 cohort. There was no significantly increased hazard of new receipt of overactive bladder medication (hazards ratio [HR]: 1.04, p = 0.88), urology consultation (HR: 1.40, p = 0.10), or cystoscopy (HR: 1.14, p = 0.50) among patients who had COVID-19, compared to the matched cohort. CONCLUSION: Surrogate markers of potential bladder dysfunction were not significantly increased in the 2-5 months after COVID-19 infection.

A prospective observational study of urinary cytokines and inflammatory response in patients with Overactive Bladder Syndrome.

BACKGROUND: Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS: To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS: A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS: The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION: The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.

Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm.

This study aimed to investigate the diagnostic values of urine cytokines in interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) patients, and to develop a novel diagnostic algorithm. Urine samples were collected from 40 IC/BPS, 40 OAB patients, and 30 controls. Commercially available multiplex immunoassays were used to analyze 31 targeted cytokines. Urine cytokine profiles were significantly different among study groups and controls. MIP-1ß showed the highest sensitivity (92.2%) for identifying diseased study patients from controls. The cytokines with high diagnostic values for distinguishing between IC and OAB included IL-10, RANTES, eotaxin, CXCL10, IL-12p70, NGF, IL-6, IL-17A, MCP-1, and IL-1RA. The diagnostic algorithm was subsequently developed according to the diagnostic values obtained. MIP-1ß was selected for the initial screening test to diagnose diseased patients and controls with diagnostic rates of 81.6% and 68.4%, respectively. As confirmation tests for IC/BPS, the diagnostic rates of eotaxin, CXCL10, and RANTES were 73.3%, 72.7%, and 69.7%, respectively. As the confirmation test for OAB, the diagnostic rate of IL-10 was 60%. Urine cytokine profiles of IC/BPS and OAB patients differed from those of controls and might be useful as biomarkers for diagnosis. A novel pilot diagnostic algorithm was developed based on these profiles.

New participant stratification and combination of urinary biomarkers and confounders could improve diagnostic accuracy for overactive bladder.

Overactive bladder (OAB) is a highly prevalent symptom complex characterised by symptoms of urinary urgency, increased frequency, nocturia, with or without urge incontinence; in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. In this study, cluster analysis was used as an objective approach for phenotyping participants based on their OAB characteristic symptoms and led to the identification of a low OAB symptomatic score group (cluster 1) and a high OAB symptomatic score group (cluster 2). Furthermore, the ability of several potential OAB urinary biomarkers including ATP, ACh, nitrite, MCP-1 and IL-5 and participants' confounders, age and gender, in predicting the identified high OAB symptomatic score group was assessed. A combination of urinary ATP and IL-5 plus age and gender was shown to have clinically acceptable and improved diagnostic accuracy compared to urodynamically-observed detrusor overactivity. Therefore, this study provides the foundation for the development of novel non-invasive diagnostic tools for OAB phenotypes that may lead to personalised treatment.

Evaluation of Urine Choline Levels in Women With and Without Overactive Bladder Syndrome.

OBJECTIVE: The objective of this study was to determine whether levels of choline (Ch) differ in women with and without overactive bladder (OAB) symptoms. METHODS: New patients were evaluated using the overactive bladder symptom score; Medical, Epidemiologic, and Social Aspects of Aging (MESA) urgency incontinence questionnaire; and Impact Questionnaire 7 and provided a urine sample. Patients were stratified into asymptomatic controls, scoring 0 on overactive bladder symptom score and the MESA questionnaire, and patients with OAB and urgency incontinence (OAB-wet). Patients with conditions predisposing to OAB or had a history of OAB treatment were excluded. Choline detection was accomplished using a commercially available kit. Wilcoxon rank sum test and Fisher exact test were used to express differences between groups. Spearman ρ correlation was used to determine the relationship between Ch and questionnaire scores. Logistic regression was used to identify significant variables associated with OAB. RESULTS: Sixty-three women were included in the final analysis. Patients with OAB-wet were older (P = 0.001), more likely to be obese (P = 0.04), had greater apical descent (P = 0.02), were more likely to be postmenopausal (P = 0.01), and were more likely to have stress incontinence (P = 0.005). Choline was 34.8% lower in OAB compared with the controls (P = 0.014). Lower Ch levels were associated with higher MESA (Spearman ρ = -0.311, P = 0.03). After logistic regression, lower Ch (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.96-0.98), age (aOR, 1.12; 95% CI, 1.08-1.18), and body mass index (aOR, 1.09; 95% CI, 1.01-1.18) were significantly associated with OAB-wet. CONCLUSIONS: Choline levels are significantly decreased in women complaining of OAB with urgency incontinence, and lower levels are associated with higher MESA scores.

Urinary Biomarkers in Overactive Bladder: Revisiting the Evidence in 2019.

CONTEXT: In overactive bladder (OAB), after an initial outbreak of research, it is more consensual that biomarkers may be better used to phenotype patients. Herein, we revisit this topic, including some of the most promising biomarkers. OBJECTIVE: To provide a comprehensive analysis of the actual role of biomarkers in OAB. EVIDENCE ACQUISITION: A PubMed-based literature search was conducted, including the most relevant articles published in the last 15 yr, on nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), adenosine triphosphate (ATP), genomics, and microbiota as OAB biomarkers. Articles with no full text available or not written in English were excluded. Additional reviews were included. EVIDENCE SYNTHESIS: Urinary NGF, BDNF, and ATP are increased in many OAB patients. These biomarkers can help identify OAB phenotypes and select the ideal candidates for new therapies directed to neurotrophic and purinergic pathways. Circulating urinary miRNA may be useful for establishing the ideal moment for bladder outlet obstruction relief and will eventually lead to the development of therapeutic agents that inhibit or reverse fibrotic pathways in the bladder. Urinary microbiota seems to be related to OAB symptoms, in particular urgency urinary incontinence, and may have strong implications in the prevention, diagnosis, and treatment of OAB. CONCLUSIONS: In the future, physicians may consider the use of biomarkers to identify distinct OAB phenotypes, with distinct causal mechanisms, selecting patients for specific target therapies with expected better outcomes. PATIENT SUMMARY: Overactive bladder biomarkers can be useful for phenotype patients and for selecting more effective target therapies.

Urinary nerve growth factor: a biomarker for detrusor overactivity in children? A meta-analysis and trail sequential analysis.

PURPOSE: Based on, previously, a systematic review, urinary nerve growth factor (NGF) has emerged as one potentially noninvasive biomarker for detrusor overactivity (DO) in adults. We performed this systematic review to explore if NGF is a biomarker for DO in children. METHODS: A literature search was conducted in PubMed, Embase, Web of science, and Cochrane Library. Copies of all relevant articles were retrieved for quality assessment and data abstraction by two reviewers. Primary outcome was pooled standardized mean difference (SMD) for NGF/Cr (NGF normalized to urine creatinine) level between DO group and controls. RESULTS: Three case-control studies published from 2012 to 2016 were included with 74 patients and 70 controls. Children with DO had a significant higher baseline urinary NGF/Cr level compared to controls (SMD = 2.48, 95%CI = 0.85-4.10, P < 0.01). After treatment, the level of NGF/Cr decreased significantly compared to baseline level at 6th month time points (SMD = 0.94, 95%CI = 0.03-1.86, P = 0.04). We calculated the required information size to 99 patients for comparison of urinary NGF/Cr level between DO and controls by trail sequential analysis (TSA). CONCLUSION: Based on this systematic review, NGF/Cr may be a noninvasive biomarker for DO in children in the future. However, based on TSA, more original studies are needed to clarify the role of NGF/Cr in the biomarker effect.

Value of Urinary Brain-Derived Neurotrophic Factor Levels on the Assessment of Botulinum Toxin Type A Treatment for Neurogenic Detrusor Overactivity in Children with Myelodysplasia.

PURPOSE: Urinary cytokines are proposed to predict urodynamic findings and outcome of intradetrusor botulinum neurotoxin type A injection in children with myelodysplasia. The relationship between urinary brain-derived neurotrophic factor and neurogenic and nonneurogenic detrusor overactivity has been shown as well. We prospectively investigated the effect of intradetrusor botulinum neurotoxin type A injection on urine brain-derived neurotrophic factor levels in children with nonneurogenic detrusor overactivity due to myelodysplasia. MATERIALS AND METHODS: Urine samples of 23 children with nonneurogenic detrusor overactivity due to myelodysplasia were collected and analyzed before and 1 and 3 months after intradetrusor botulinum neurotoxin type A injection, and urodynamics were performed before and 6 weeks after injection. Brain-derived neurotrophic factor levels and urodynamic findings were analyzed and statistical comparisons were done. RESULTS: Mean ± SD age was 100.0 ± 34.5 months. Ratio of girls to boys was 2.8. Brain-derived neurotrophic factor levels significantly decreased (p <0.006), and maximum cystometric capacity and maximum detrusor pressure improved significantly following intradetrusor botulinum neurotoxin type A injection compared to preoperatively (p <0.001). No statistical correlations were determined between brain-derived neurotrophic factor levels and urodynamics. Of all analyses only bladder compliance 5 ml/cm H2O or less vs greater than 5 ml/cm H2O at postoperative urodynamics was associated with statistically increased urine brain-derived neurotrophic factor levels, suggesting that increased urine brain-derived neurotrophic factor predicts treatment failure. CONCLUSIONS: The present study does not suggest that urine brain-derived neurotrophic factor is a reliable followup marker in children with nonneurogenic detrusor overactivity due to myelodysplasia. However, this factor may have a role in treatment planning, which needs to be established in future large prospective studies.

[Sensitivity and specificity of urinary and serum neurotrophins in the diagnosis of neurogenic detrusor overactivity in multiple sclerosis].

Lower urinary tract dysfunction is common among neurological patients. Traditionally, the basic method of diagnosis is a complex urodynamic study. In recent years, many studies have focused on the search for new non-invasive diagnostic modalities. In particular, neurotrophins are considered as potential biological markers of a neurogenic bladder. AIM: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) and brain neurotrophic factor (BDNF) in MS patients as markers of detrusor overactivity. MATERIALS AND METHODS: The study comprised 20 patients with multiple sclerosis, who complained of voiding problems. The control group consisted of 20 people without neurological diseases, lower urinary tract symptoms and detrusor overactivity estimated by filling cystometry. Apart from standard laboratory tests, diagnostic evaluation included a complex urodynamic study, ultrasound of the urinary tract, cystoscopy, testing serum and urinary NGF and BDNF using the enzyme immunoassay. The diagnostic significance of neurotrophins was evaluated using ROC analysis. RESULTS: According to the ROC analysis, the diagnostic sensitivity and specificity of serum NGF as a marker of detrusor hyperactivity was 57% and 93%, respectively (for serum NGF more or equal 26 pg/ml). The quality of the test according to the expert scale of AUC values was "very good" (AUC=0.806). Detecting NGF in patients urine was less effective. The sensitivity and specificity were 52% and 40%, respectively (for NGF more or equal 6 pg/ml). The quality of the test according to the expert scale of AUC values was "average" (AUC=0.64). The serum BDNF demonstrated high sensitivity (90%) and low specificity (23%), AUC=0.56. The urinary BDNF was more informative, (AUC=0.65). The combination of all four markers provides a sensitivity of 85.7% and a specificity of 66.7% (AUC=0.824). CONCLUSIONS: Testing serum and urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity. The NGF is a highly specific biomarker, while the BDNF is highly sensitive. Combined testing for serum NGF and BDNF is most informative.

Nerve Growth Factor Levels are Associated with Overactive Bladder Symptoms and Long-Term Treatment Outcome after Transurethral Resection of the Prostate in Patients with Benign Prostatic Hyperplasia.

PURPOSE: We investigated changes in urinary nerve growth factor in patients with benign prostatic hyperplasia after transurethral prostate resection. We also assessed the association between nerve growth factor and changes of overactive bladder symptoms and long-term treatment outcomes after surgery. MATERIALS AND METHODS: This was a prospective study of 178 patients at Peking University People's Hospital with benign prostatic hyperplasia between January 2011 and January 2013. Urinary nerve growth factor levels were determined preoperatively using a commercial enzyme-linked immunosorbent assay kit. We also determined prostate volume, I-PSS (International Prostate Symptom Score), quality of life, OABSS (Overactive Bladder Symptom Score), ultrasound estimated post-void residual urine and urodynamics before surgery. Urinary nerve growth factor levels, I-PSS and OABSS were assessed again 1 year after transurethral prostate resection. RESULTS: Urinary nerve growth factor/creatinine levels differed between patients with moderate and severe lower urinary tract symptoms (mean ± SD 10.513 ± 4.255 vs 12.334 ± 4.048 pg/µmol, p = 0.002). There was no significant difference between patients with grades III/IV and V/VI bladder outlet obstruction (mean 11.285 ± 4.069 vs 11.781 ± 4.437 pg/µmol, p = 0.354). However, differences were significant for urinary nerve growth factor/creatinine levels in patients without overactive bladder, and mild, moderate and severe overactive bladder (mean 8.132 ± 3.489, 10.128 ± 3.817, 13.232 ± 3.290 and 14.029 ± 3.820 pg/µmol, respectively, p <0.001). One year after transurethral prostate resection we noted a decrease vs baseline in mean urinary nerve growth factor/creatinine (8.978 ± 4.022 pg/µmol, p <0.001), and I-PSS and OABSS (10.2 ± 5.4 and 4.3 ± 3.7, respectively, each p <0.001). Compared with the good outcome group, the fair/poor group had higher mean baseline urinary nerve growth factor/creatinine (12.319 ± 4.017 vs 11.015 ± 4.298 pg/µmol, p = 0.045), higher mean 1-year urinary nerve growth factor/creatinine (10.847 ± 4.267 vs 7.850 ± 3.419 pg/µmol, p <0.001) and a lesser mean postoperative change in urinary nerve growth factor/creatinine (1.472 ± 4.928 vs 3.165 ± 4.863 pg/µmol, p = 0.031). CONCLUSIONS: Nerve growth factor was associated with overactive bladder symptoms in patients with benign prostatic hyperplasia as well as with the assessment of successful long-term treatment outcome of bladder outlet obstruction with symptoms of overactive bladder.

Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a challenging disease, affecting thousands of people all around the world, especially women. Although there have been numerous theories regarding IC/BPS etiology, the physiopathology of the disease still remains unclear and there is a lack of certain treatment. OBJECTIVES: The aim of the study was to assess the role of nerve fibers and nerve growth factor (NGF) in the etiopathogenesis of IC/BPS symptoms by demonstrating if there is a correlation between urine NGF levels, amount of peripheral nerves in bladder mucosa and symptom severity. MATERIAL AND METHODS: A prospective clinical study was conducted with 15 IC/BPS patients and 18 controls. Urine NGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Bladder punch biopsies were obtained from 15 IC/BPS patients and 9 controls. Immunohistochemistry was performed for S-100 to highlight peripheral nerve twigs in bladder mucosa. The O'Leary-Sant Interstitial Cystitis Symptom and Problem Index (OSICSPI) was used to assess symptom severity and effects of the disease on the patients' life. RESULTS: NGF normalized to urine creatinine (NGF/Cr) levels in IC/BPS patients were significantly higher than in controls, 0.34 ±0.22 and 0.09 ±0.08 pg/mL: mg/dL, respectively (p < 0.001). The mean symptom score in IC patients was 12.27 ±2.4 (median: 12) and the mean problem score was 10.9 ±2.3 (median: 12). The mean mucosal nerve (S-100 stained) area in the IC/BPS group was significantly higher than in the controls, 2.53 ±1.90 vs 1.0 ±0.70, respectively (p = 0.018). In correlation analyses, the NGF/Cr level in IC/BPS patients was found significantly correlated with the O'Leary-Sant IC Symptom and Problem Index scores independently (p = 0.001 and p = 0.028, respectively). CONCLUSIONS: NGF seems to be a promising biomarker in IC/BPS. It may help clinicians in diagnoses and patient follow-up. Thus, unnecessary, expensive and invasive tests, interventions and treatments might be avoided.

Comparison of inflammatory urine markers in patients with interstitial cystitis and overactive bladder.

INTRODUCTION AND HYPOTHESIS: Chronic inflammatory conditions seem to be a shared characteristic in patients with interstitial cystitis (IC) and overactive bladder (OAB). Thus, we measured 40 inflammatory urine markers in IC patients with or without Hunner's lesions (HIC and NHIC respectively) and OAB patients. METHODS: Urine was collected from consecutive HIC patients, NHIC patients, and age and gender-matched OAB patients with no history of IC, recurrent urinary tract infection or bladder cancer. The diagnosis of IC was based on the Asian IC guideline criteria. A representative 40 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Statistical differences in these markers among the groups were determined by nonparametric ANOVA followed by multiple comparison test. The diagnostic efficiency of these markers was measured using receiver operating characteristic analysis. RESULTS: Vascular endothelial growth factor (VEGF), interleukin-1α (IL-1α), IL-6, and chemokines including CCL2, CCL5, CXCL1, CXCL8, and CXCL10 were significantly increased in HIC (n = 30) and NHIC (n = 30) patients compared with OAB (n = 28) patients. The significant increases in CXCL8 and CXCL10 were also found in HIC patients compared with NHIC patients. However, there were no significant differences in the other urine markers among the groups. Area under the curves for VEGF, CXCL10, CXCL8, IL-1α, CCL5, CCL2, IL-6, and CXCL1 to detect IC in these patients were 0.87, 0.86, 0.81, 0.80, 0.80, 0.71, 0.66, and 0.50 respectively. CONCLUSIONS: The increases in angiogenesis-associated proteins such as VEGF and CXCL10 may be pathophysiologically important for the development of IC.

Prosultiamine for treatment of lower urinary tract dysfunction accompanied by human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis.

OBJECTIVES: To evaluate oral prosultiamine treatment in patients with overactive bladder accompanied by human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. METHODS: This was a prospective, single-center, open-label study. Patients received oral prosultiamine (300 mg) once daily in the morning, and the overactive bladder symptom score and urine levels of overactive bladder-related biomarkers (nerve growth factor/creatinine and adenosine triphosphate/creatinine) 12 weeks after the initial administration were compared with the baseline values. In addition, the urodynamic parameters, including involuntary detrusor contraction and detrusor sphincter dyssynergia, were evaluated before and after treatment. RESULTS: A total of 16 patients were recruited for this clinical study. In the overactive bladder symptom score, night-time frequency, urgency and the total score improved after oral prosultiamine treatment (P = 0.028, 0.001 and 0.004, respectively). Both urinary nerve growth factor/creatinine and adenosine triphosphate/creatinine levels decreased significantly after the treatment (P = 0.004 and 0.017, respectively). Urodynamic studies showed that the maximum cystometric capacity increased significantly after the treatment. However, the symptoms disappeared because of the treatment in six of 10 patients with involuntary detrusor contraction (60%) and three of seven patients with detrusor sphincter dyssynergia (42.9%). There were no serious adverse events. CONCLUSIONS: The changes in urodynamic parameters and urine levels of overactive bladder-related markers suggest that oral prosultiamine is a safe and effective treatment for overactive bladder with human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis.

Development of novel and non-invasive diagnostic markers for lower urinary tract symptoms using urothelial cells in voided urine.

OBJECTIVES: We evaluated the association between lower urinary tract symptoms (LUTS) and the expression of connexin (Cx) and transient receptor potential (TRP) channel on urothelial cells non-invasively collected from voided urine in humans. METHODS: A total of 55 patients (36 males and 19 females, median age: 71 years old), who were followed up at University of Yamanashi Hospital, were enrolled in the present study. Urothelial cells were collected from voided urine of patients, and the mRNA expression of each subtype of Cxs and TRP channels was measured using quantitive real-time reverse transcription polymerase chain reaction. We then analyzed the correlation between the expression of Cxs and TRP channels and symptom scores in International Prostate Symptom Scoreand Overactive Bladder Symptom Score, in addition to Interstitial Cystitis Symptom Index (ICSI) from only interstitial cystitis (IC) patients. RESULTS: Non-adjusted statistical procedure using Spearman's rank-correlation showed that there were significant correlations between the following expressions and symptom scores; (positive correlations) Cx26 versus urgency score, Cx40 versus nocturia, TRPM2 versus intermittency, TRPV1 versus urge incontinence, (negative correlation) Cx40 versus intermittency, TRPM7 versus pollakisuria. However, a multiple comparison adjustment using Bonferroni correction showed that only Cx40 had a trend of correlation with nocturia in ICSI. CONCLUSIONS: The expressions of Cxs and TRP channels on urothelial cells in voided urine could be related to LUTS. Further analysis of urothelial cells in voided urine has the potential to reveal the mechanism of the LUTS and develop new markers with non-invasive methods.

Inflammatory Urinary Cytokine Expression and Quality of Life in Patients With Overactive Bladder.

OBJECTIVE: The aims of this study were to analyze levels of selected inflammatory urinary cytokines/chemokines in subjects with overactive bladder (OAB) and to determine if cytokine/chemokine levels correlate with quality of life and symptom distress. METHODS: This prospective, case-control pilot analysis included 23 women with OAB and 22 control subjects. Overactive bladder subjects were enrolled if they had symptoms of urinary frequency, urgency, or urge incontinence for more than 3 months and urodynamic evidence of detrusor overactivity. Control subjects denied urinary symptoms. Subjects and control subjects were excluded if they had known inflammatory bladder or systemic conditions, cystitis, stones, or recent anticholinergic use. Urine samples were collected from each subject and control. Subjects filled out the Incontinence Quality of Life Questionnaire and the Urinary Distress Inventory Questionnaire 6. Cytokine/chemokine levels were determined using the multiplexed Meso Scale Discovery Platform and were corrected for urinary creatinine concentrations. Statistical analysis comparing cytokine/chemokine levels was performed using the Mann-Whitney U test; relationships between cytokine/chemokine and questionnaire scores were calculated with Spearman correlation coefficient. RESULTS: Subjects with OAB had significantly lower urinary interleukin 10 (IL-10), IL-12-p70, and IL-13 levels compared with control subjects. Interleukin 1 correlated with worsening symptom distress on Urinary Distress Inventory Questionnaire 6. CONCLUSIONS: To our knowledge, this is at present the only study correlating inflammatory cytokine/chemokine levels in women with OAB with quality of life and distress. Interleukin 1 signified worsening distress, whereas IL-10, IL-12p70, and IL-13 were the only cytokines found at different levels in subjects. Our findings support a larger study in order to evaluate the value of urinary cytokines/chemokines as potential biomarkers.

[PATHOGENETIC FEATURES OF THE DEVELOPMENT OF OVERACIVE BLADDER IN WOMEN].

The aim of the research was to study the pathogenetic features of the development of the overactive bladder (OAB) in women. 107 women with OAB and a control group of 29 healthy women were involved into the study. The hormonal status was studied based on the determination of serum concentrations of luteinizing hormone (LH), stimulating hormone (FSH), estradiol and progesterone. The urine levels of interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-8 (IL-8), tumor necrosis factor ά (TNF-ά) and macrophage chemotactic protein-1 (MCP-1) were assessed. Decreased level of estradiol was detected in 26.47% of women of reproductive age. Elevated urine levels of MCP-1 and IL-8 were found in 35.5% of patients. The obtained data testify to the possible pathogenetic role of inflammatory changes in the bladder wall, as well as hypoestrogenism in women of reproductive age in the development of OAB.

Association of increased urine brain derived neurotrophic factor with lower urinary tract symptoms in men with benign prostatic hyperplasia.

Urinary brain-derived neurotrophic factor (BDNF), an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia (BPH). We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms (LUTS) in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score (IPSS) was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity (DO) in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine (Cr) levels. Seventy-six BPH patients were divided into moderate LUTS group (n=51, 720) according to the IPSS. Of the 76 BPH patients, DO was present in 34 (44.7%) according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS (8.29±3.635, P<0.0001) and severe LUTS (11.8±6.44, P<0.0001) than normal controls (1.71±0.555). Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS (11.8±6.44 vs. 8.29±3.635, P=0.000). The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker for the diagnosis of DO in BPH patients.

Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis.

OBJECTIVE: The previously reported association between urinary nerve growth factor (NGF) and overactive bladder (OAB) was controversial. We performed this meta-analysis based on current available studies to sum up all evidence on this association. METHODS: Studies were identified by searching PubMed, Embase, and Cochrane library from inception to September 2016. Pooled standardized mean difference (SMD) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of 17 published studies were included in this meta-analysis. Among the studies considered, patients with OAB had a significant higher baseline urinary NGF/Cr (NGF normalized to urine creatinine) level compared to those of controls (SMD = 0.74, 95%CI = 0.43-1.04, P < 0.00001). After treatment, the level of NGF/Cr decreased significantly in OAB group. However, there was no significant difference between patients with IC (interstitial cystitis)/PBS (painful bladder syndrome) and patients with overactive bladder (OAB) with regard to the urinary NGF/Cr level (SMD = 0.18, 95%CI = -0.06 to 0.41, P = 0.14). There was a statistically significant heterogeneity among included studies (P < 0.00001, I2 = 85%). No obvious evidence of significant publication bias was detected. In conclusion, this meta-analysis indicates that urine NGF/Cr may be a useful biomarker for OAB in the future. Because of lack of specificity, it seems that NGF/Cr cannot be used as a biomarker for OAB at present. Nevertheless, combined with other biological indicators may improve its specificity in diagnosis. More high quality studies that control the compounding factors strictly should be conducted in the future.

The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia.

AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA). Urine samples of each child were collected before and after BoNT-A injections, specifically at the first and third postoperative months. Urine samples were analyzed with ELISA method and NGF, TGF-Beta-1, and TIMP-2 levels were measured. Urine marker levels and clinical findings were assessed for statistical significance with Wilcoxon Signed Ranks Test and Friedman Test. RESULTS: A total of 15 children (5 boys and 10 girls) were assigned as the study group. Mean age of the patients was 7.1 ± 2.5 years (range 2.5-11). A statistically significantly decline was observed in urinary TGF-Beta-1 and NGF levels following BoNT-A injections, compared to the preoperative levels (P < 0.05). TIMP-2 levels also tend to decrease following BoNT-A injections but this was not statistically significant compared to the preoperative levels. CONCLUSION: This preliminary study, suggests urinary TGF-Beta-1 and NGF as a potent marker in children with NDOA, as they decline following BoNT-A injection. Further studies are needed in identifying their special role in assessing treatment success after invasive interventions.