Role of urine glycosaminoglycan levels in the diagnosis and follow-up in men with lower urinary tract symptoms.

OBJECTIVE: The aim of this study was to investigate whether urinary glycosaminoglycans (GAG) levels reflect clinical status in men with lower urinary tract symptoms and if they could be used as a marker in management of overactive bladder (OAB). METHODS: A total of 34 patients were recruited who were admitted with LUTS and diagnosed as having clinically bladder outlet obstruction (BOO) due to prostate enlargement. These newly diagnosed, never treated patients underwent routine investigation, consisting of history, physical examination, PSA, ultrasound, uroflowmetry, assessment of symptoms scored by both International Prostate Symptom Score (IPSS) and Marmara- Overactive Bladder Questionnaire (M-OBQ). The patients were divided into two groups as those with an initial M-OBQ score < 12 (group 1) and ≥ 13 (group 2). Alfa blocker was initiated in eligible patients. Further evaluations included prostate volume measurement, pre- and post-treatment urinary GAG levels, IPSS and M-QAOB values and maximum urine flow rate (Qmax). RESULTS: Before treatment, urinary GAG level was 21.5 mg/gCr (6.1-45.5) in Group 1, and 23.35 mg/gCr (15.6-32.6) in Group 2 (p =0.845). After the treatment, the GAG level in Group 1 and Group 2 were found to be 19.8 mg/gCr (7.4-70.5) and 18 (7.6- 41.7), respectively (p = 0.511). No difference in GAG levels was found in subgroup analysis for patients with or without OAB. CONCLUSIONS: In recent years, there have been many studies investigating the relationship between LUTS and urinary markers. However, in our prospective study, no relationship was found between pre- and post- treatment urinary GAG levels in patients with LUTS with or without OAB.

Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

INTRODUCTION: Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a ß3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. MATERIALS AND METHODS: Urinary NGF and BDNF levels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50 mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3 months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. RESULTS: Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). CONCLUSION: Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

Predicting muscarinic receptor occupancy in human bladder mucosa from urinary concentrations of antimuscarinic agents for overactive bladder.

To assess the pharmacologically relevant and selective muscarinic receptor occupancy in the bladder mucosa, we considered not only plasma drug concentrations but also urinary drug concentrations. The purpose of this study was to predict muscarinic receptor occupancy in the human bladder mucosa based on urinary concentrations in response to clinical dosages of antimuscarinic agents used to treat overactive bladder. The calculated mean plasma or serum unbound steady state concentrations were 0.06-11 nM in clinical dosages of five antimuscarinic agents. Urinary concentrations calculated from the mean plasma or serum and renal clearance ranged between 19 nM and 2 µM, which were >10-fold higher than the Ki values for bladder muscarinic receptors excluding propiverine. Bladder mucosal muscarinic receptor occupancy estimated from the urinary concentrations and the Ki values was >90 % at a steady state in clinical dosages of five antimuscarinic agents. The bladder muscarinic receptor occupancy was higher than that in the parotid gland calculated based on the mean plasma or serum unbound concentrations and Ki values for muscarinic receptors in the parotid gland. These results suggest that sufficient and selective muscarinic receptor occupancy by antimuscarinic agents, to exert pharmacological effects, in the bladder mucosa can be predicted using urinary concentrations.

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.

Diagnostic value of nerve growth factor in detrusor overactivity: a study on women with mixed urinary incontinence.

OBJECTIVE: Urinary incontinence has a profound impact on women's quality of life. Studies have shown that changes in urinary protein levels could be a potential diagnostic biomarker in some urological diseases. The aim of present study is to determine the diagnostic value of nerve growth factor (NGF) in women with mixed urinary incontinence (MUI) as a diagnostic biomarkers of detrusor overactivity (DO). METHODS: Seventy women aged between 20 and 75 years with MUI were enrolled in this prospective study. All participants underwent urodynamic study. Urine NGF levels were measured using an ELISA method. NGF level was compared between groups using Mann-Whitney U test. Receiver Operator Characteristic (ROC) analysis was employed to evaluate the diagnostic performance of urinary NGF. RESULTS: The results showed that the median (min, max) of NGF in patients with DO was significantly higher in comparing to its level in women without DO [184.10 (31, 346.60) pg/ml vs. 151.80 (21, 210.70)], respectively (P = 0.035). Using receiver-operator characteristics analysis, the threshold urinary NGF value of 102.00 pg/ml provided a sensitivity of 88% and specificity of 40% in diagnosing DO, PPV of 39.1%, and NPV of 88.2%, positive likelihood ratio 2.18 and negative likelihood ratio of 0.45 (P = 0.02). CONCLUSION: Based on high sensitivity and low specificity, we can conclude that NGF can be a good tool for ruling out the OAB when the test is negative. However, the future investigations are needed to expand the observed correlation in larger groups of women with DO.

Urinary cytokines in women with refractory detrusor overactivity: A longitudinal study of rotating antibiotic versus placebo treatment.

Over 50% of women with detrusor overactivity (DO), who do not respond to therapy have been shown to have bacteriuria, which may stimulate the release of inflammatory cytokines than can enhance nerve signalling, leading to symptoms of urgency. This study made use of a consecutive series of urine samples collected from women with refractory DO, who participated in a clinical trial of rotating antibiotic therapy. The aim was to determine the effect of bacteriuria and antibiotic treatment on the levels of urinary cytokines, and to correlate the cytokine concentration with patient outcome measures relating to urgency or urge incontinence. The urinary cytokines chosen were IL-1α, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, CXCL10 (IP-10), MCP-1 and TNF-α. The presence of bacteriuria stimulated a significant increase in the concentrations of IL-1α (P 0.0216), IL-1 receptor antagonist (P 0.0264), IL-6 (P 0.0003), IL-8 (P 0.0043) and CXCL-10 (P 0.009). Antibiotic treatment significantly attenuated the release of IL-1α (P 0.005), IL-6 (P 0.0027), IL-8 (P 0.0001), IL-10 (P 0.049), and CXCL-10 (P 0.042), i.e. the response to the presence of bacteria was less in the antibiotic treated patients. Across the 26 weeks of the trial, antibiotic treatment reduced the concentration of five of the nine cytokines measured (IL-1α, IL-6, IL-8, IL-10 and CXCL-10); this did not reach significance at every time point. In antibiotic treated patients, the urinary concentration of CXCL-10 correlated positively with four of the six measures of urgency. This study has shown that cytokines associated with activation of the innate immune system (e.g. cytokines chemotactic for or activators of macrophages and neutrophils) are reduced by antibiotic therapy in women with refractory DO. Antibiotic therapy is also associated with symptom improvement in these women, therefore the inflammatory response may have a role in the aetiology of refractory DO.

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.

Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome.

PURPOSE: Given the disputable link between nerve growth factor (NGF) and overactive bladder syndrome (OAB) and the lack of studies on its precursor (proNGF) in OAB, the aim of the study was to identify changes in the urinary levels of NGF and its proteolytic enzymes in aging women with OAB. METHODS: We examined the urinary proNGF/NGF ratio and its processing enzymes in aging women (50-80 years), comparing 20 controls and 20 subjects with OAB. RESULTS: In contrast to previous reports correlating NGF to OAB symptoms, we found that proNGF/NGF ratio in the OAB group was twice as high compared to controls (p = 0.009) with a lower NGF levels in women with OAB without statistical significance [1.36 (Q1, Q3: 0.668, 2.39) vs. 1.7 (Q1, Q3: 1.27, 3.045) pg/mg creatinine in control group, p = 0.05]. Enzymatic activity of MMP-7, the main enzyme for extracellular proNGF maturation, was significantly increased in the OAB group and correlated positively with scores of OAB symptoms questionnaires. However, this was counteracted by several-folds increase in the MMP-9 enzyme responsible for NGF proteolysis. While these findings highlight the importance of changes in the proteolytic enzymes to maintain proNGF/NGF balance in OAB, analysis of covariates showed that these changes were attributed to age, insulin resistance and renal function. CONCLUSION: NGF proteolysis imbalance can be clinically meaningful in OAB related to aging, rendering it as a potential therapeutic target. However, other age-related factors such as insulin resistance and renal function may contribute to the relationship between NGF and aging-related OAB phenotype.

The profile of urinary biomarkers in overactive bladder.

AIMS: In overactive bladder (OAB) research, different biomarkers have been proposed as diagnostic tools and may be used to create individual patient profiles. Assessing the diagnostic performance of biomarkers would better outline their utility. Therefore, our aim was to investigate the diagnostic value of four urinary biomarkers: human brain derived neurotrophic factor (hBDNF), malondialdehyde (MDA), h nerve growth factor (hNGF) and h 8-hydroxydeoxyguanosine in women with OAB. These are neurotrophins/oxidative stress markers that have been linked to lower urinary tract symptoms. METHODS: A total of 105 women were included in the study and distributed in two groups: a group with OAB (n = 53) and a control group (n = 50). The levels of the biomarkers were determined using enzyme-linked immunosorbent assay technique and they were compared between the groups. If the Mann-Whitney test demonstrated a statistically significant difference, receiver operating curves (ROC) analysis was undertaken. RESULTS: When normalized to urinary creatinine, hBDNF, MDA, and hNGF showed significantly increased values in women with OAB as compared to controls, whereas 8-OHdG showed no significant difference. The diagnostic performance of these biomarkers was analyzed based on the area under the ROC curve (AUC). MDA had the highest AUC (0.75), followed by hNGF (0.69) and hBDNF (0.67). CONCLUSIONS: Our findings suggest that MDA, a relatively novel biomarker in OAB research, has a fair performance as a diagnostic tool for OAB. Moreover, urinary neurotrophins (NGF and BDNF) as biomarkers may have a role in the diagnostic pathways of women with OAB symptoms.

The impact of microalbuminuria on overactive bladders: Results from a community-based four-year longitudinal study in Japan.

AIMS: To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB). METHODS: This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial-ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis. RESULTS: This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P = .001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15-4.60; P = .002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15-3.23; P = .013) were independent risk factors for ΔOABSS > 1. CONCLUSIONS: Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation.

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 profiles in patients with neurogenic detrusor overactivity according to their neurological condition.

OBJECTIVES: The aim of this study was to investigate the disease-specific urinary levels variations of neurotrophins (NGF, BDNF), mediators of inflammation (TGFß-1, PGE-2) and markers of extracellular matrix alterations (TIMP-2) in patients with multiple sclerosis (MS) spinal cord injury (SCI), or spina bifida (SB), and neurogenic detrusor overactivity (NDO). METHODS: A prospective single-center study was conducted between March 2015 and March 2017. Patients aged over 18 years old, with neurological disease, with a urodynamic diagnosis of NDO were included. The urinary levels of NGF, BDNF, TIMP-2, PGE 2, and TGF-ß1 were measured using dedicated ELISA kits. RESULTS: Forty-one patients were included: 6 with MS, 20 with SCI, and 15 with spina bifida. The average urinary level of NGF/Cr was significantly higher in MS patients compared to other neurologic populations (8 vs. 0.56 vs. 1.25 pg/mg of creatinine; p = 0.001) as well for the average urinary level of BDNF (88.3 vs. 5 vs. 4.8 pg/mg of creatinine; p < 0.0001). SCI patients had a significantly lower level of TGFß-1 than SB patients (p = 0.04). The urinary level of PGE2 was significantly correlated with the Body Mass Index (r = 0.61; p = 0.0002). CONCLUSION: All NDO may not be created equal from the molecular standpoint. Multiple sclerosis patients had higher urinary levels of neurotrophins than in other neurologic populations with NDO. Urinary TGFß-1, a strong determinant of extracellular matrix, was significantly higher in spina bifida patients compared to SCI patients. These findings underscore the importance of using and interpreting those possible urinary markers in a disease-specific fashion.

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.

Measuring urinary 8-hydroxy-2'-deoxyguanosine and malondialdehyde levels in women with overactive bladder.

Purpose: In this study, we aimed to explain the role of oxidative stress in women with overactive bladder (OAB) by investigating the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and malondialdehyde (MDA), an indicator of lipid peroxidation. Materials and Methods: A total of 90 women were included in the study: 45 female patients diagnosed with OAB at Hopa State Hospital Urology Polyclinic and 45 healthy women without any metabolic or neurologic disease. Levels of MDA and 8-OHdG were measured in 24-hour urine samples for all subjects. Results: Urinary levels of MDA and 8-OHdG were significantly higher in the OAB group than in the control group (p<0.001). A significant positive correlation (p<0.001) was found between the measurements of 8-OHdG and MDA. Conclusions: Oxidative stress may be important in the pathophysiology of OAB, because levels of 8-OHdG and MDA are increased. Increased levels of 8-OHdG may be due to damaged nuclear and mitochondrial DNA as a result of oxidative attacks caused by free radicals. Nevertheless, further randomized and prospective studies with larger patient populations are needed.

Effectiveness and safety of acupuncture for elderly overactive bladder population in Hong Kong: study protocol for a randomized controlled trial.

BACKGROUND: Overactive bladder (OAB) is defined as "urgency, with or without urge incontinence, usually with frequency and nocturia". Acupuncture is one of the most popular alternative treatment methods for OAB. Little established evidence is available to support the effectiveness of acupuncture for OAB. This study is a pioneer randomized, double-blinded, sham-controlled trial to assess the effectiveness and safety of acupuncture in the elderly population with overactive bladder in Hong Kong. METHODS/DESIGN: This is a randomized, double-center, patient and outcome assessor blinded, sham-controlled trial. The study sample size is 100 patients. Eligible subjects aged between 60 to 90 years old will be recruited into this study. All subjects will be randomly allocated into the active acupuncture group or sham acupuncture group in a 1: 1 ratio. Participants who are allocated into the active acupuncture group will receive a standardized 30-min real acupuncture treatment session for a total of 16 sessions on the top of standard routine care, whilst those who are randomized to the sham acupuncture arm will receive sham acupuncture in addition to standard routine care. Non-penetrating needles will be utilized as sham acupuncture. The primary outcome measure is the 7-day voiding diary and the secondary outcome measures are urine nerve growth factor (NGF) level, the Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI-6) and OAB Symptom Score (OABSS). All outcome measures will be collected at baseline, the end of treatment and 3 months after treatment completion. DISCUSSION: The objectives of this study include (1) to evaluate the effectiveness and safety of acupuncture treatment in patients with OAB on reduction in the frequency of incontinence episodes as derived from a 7-day voiding diary, (2) to evaluate whether acupuncture treatment could improve subjective symptoms in patients with OAB and (3) to examine the feasibility of using NGF as a biomarker for overactive bladder and test correlation with the effectiveness of acupuncture intervention. The finding of this study will provide preliminary evidence on the effectiveness and safety of acupuncture for treatment of OAB. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16010048 . Registered on 29 Nov 2016.