Yuan-Hong Jiang

Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment - A prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial.

Intravesical onabotulinumtoxinA (BoNT‐A) injection is a beneficial treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), yet its therapeutic efficacy remains to be validated. This study tests efficacy and safety of intravesical BoNT‐A injections for treatment of IC/BPS.

Increased Pro-Inflammatory Cytokines, C-Reactive Protein and Nerve Growth Factor Expressions in Serum of Patients with Interstitial Cystitis/Bladder Pain Syndrome

Objective The etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS. Methods Serum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1β, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1β, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated. Results The results showed that CRP level (pu200a=u200a0.031), NGF (pu200a=u200a0.015) and pro-inflammatory cytokines/chemokine IL-1β, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1β and IL-8 (p<0.001), IL-6 and CRP (pu200a=u200a0.01), IL-6 and IL-8 (pu200a=u200a0.02), and IL-6 and TNF-α (pu200a=u200a0.03). Conclusion Increased pro-inflammatory cytokines/chemokine (IL-1β, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.

Efficacy and safety of intravesical onabotulinumtoxinA injection on elderly patients with chronic central nervous system lesions and overactive bladder.

Purpose Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson’s disease (PD) and dementia. Materials and Methods Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups. Results A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions. Conclusion Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment.

Decrease of Urinary Nerve Growth Factor but Not Brain-Derived Neurotrophic Factor in Patients with Interstitial Cystitis/Bladder Pain Syndrome Treated with Hyaluronic Acid

Aims To investigate urinary nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in interstitial cystitis/bladder pain syndrome (IC/BPS) patients after hyaluronic acid (HA) therapy. Methods Thirty-three patients with IC/BPS were prospectively studied; a group of 45 age-matched healthy subjects served as controls. All IC/BPS patients received nine intravesical HA instillations during the 6-month treatment regimen. Urine samples were collected for measuring urinary NGF and BDNF levels at baseline and 2 weeks after the last HA treatment. The clinical parameters including visual analog scale (VAS) of pain, daily frequency nocturia episodes, functional bladder capacity (FBC) and global response assessment (GRA) were recorded. Urinary NGF and BDNF levels were compared between IC/BPS patients and controls at baseline and after HA treatment. Results Urinary NGF, NGF/Cr, BDNF, and BDNF/Cr levels were significantly higher in IC/BPS patients compared to controls. Both NGF and NGF/Cr levels significantly decreased after HA treatment. Urinary NGF and NGF/Cr levels significantly decreased in the responders with a VAS pain reduction by 2 (both p < 0.05) and the GRA improved by 2 (both p < 0.05), but not in non-responders. Urinary BDNF and BDNF/Cr did not decrease in responders or non-responders after HA therapy. Conclusions Urinary NGF, but not BDNF, levels decreased significantly after HA therapy; both of these factors remained higher than in controls even after HA treatment. HA had a beneficial effect on IC/BPS, but it was limited. The reduction of urinary NGF levels was significant in responders, with a reduction of pain and improved GRA.

Increased Serum Adipokines Implicate Chronic Inflammation in the Pathogenesis of Overactive Bladder Syndrome Refractory to Antimuscarinic Therapy

Objectives Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy. Methods Thirty consecutive patients with OAB-dry (nu200a=u200a16) or OAB-wet (nu200a=u200a14) refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups. Results The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls. Conclusions Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were not relevant to medical diseases.

Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology.

Lower urinary tract symptoms (LUTS) are common in various bladder disorders. This study investigated urothelial dysfunction and chronic inflammation in the urothelium in different types of lower urinary tract dysfunction (LUTD), which causes bladder storage symptoms.

International Prostatic Symptom Score-voiding/storage subscore ratio in association with total prostatic volume and maximum flow rate is diagnostic of bladder outlet-related lower urinary tract dysfunction in men with lower urinary tract symptoms.

Objectives The aim of this study was to investigate the predictive values of the total International Prostate Symptom Score (IPSS-T) and voiding to storage subscore ratio (IPSS-V/S) in association with total prostate volume (TPV) and maximum urinary flow rate (Qmax) in the diagnosis of bladder outlet-related lower urinary tract dysfunction (LUTD) in men with lower urinary tract symptoms (LUTS). Methods A total of 298 men with LUTS were enrolled. Video-urodynamic studies were used to determine the causes of LUTS. Differences in IPSS-T, IPSS-V/S ratio, TPV and Qmax between patients with bladder outlet-related LUTD and bladder-related LUTD were analyzed. The positive and negative predictive values (PPV and NPV) for bladder outlet-related LUTD were calculated using these parameters. Results Of the 298 men, bladder outlet-related LUTD was diagnosed in 167 (56%). We found that IPSS-V/S ratio was significantly higher among those patients with bladder outlet-related LUTD than patients with bladder-related LUTD (2.28±2.25 vs. 0.90±0.88, p<0.001). TPV was similar between the two groups; however, in contrast to patients with bladder-related LUTD, patients with bladder outlet-related LUTD had higher detrusor voiding pressure, lower Qmax values, and greater postvoid residual volumes. The combination of TPV30 ml and Qmax10 ml/sec had a PPV of 68.8% and a NPV of 53.5% for bladder outlet-related LUTD. When IPSS-T12 or IPSS-T15 was considered as an additional criterion, PPV increased to 75.0% and 78.5%, respectively, and the NPV decreased to 50.9% and 50.2%, respectively. When IPSS-V/S>1 or >2 was factored into the equation instead of IPSS-T, PPV were 91.4% and 97.3%, respectively, and NPV were 54.8% and 49.8%, respectively. Conclusions Combination of IPSS-T with TPV and Qmax increases the PPV of bladder outlet-related LUTD. Furthermore, including IPSS-V/S>1 or >2 into the equation results in a higher PPV than IPSS-T. IPSS-V/S>1 is a stronger predictor of bladder outlet-related LUTD than IPSS-T.

Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings.

To investigate urothelial dysfunction and suburothelial inflammation in patients with chronic SCI at different spinal cord levels.

Revisiting the Role of Potassium Sensitivity Testing and Cystoscopic Hydrodistention for the Diagnosis of Interstitial Cystitis.

Objectives To revisit the diagnostic roles of cystoscopic hydrodistention and the potassium sensitivity test (PST) for the diagnosis of interstitial cystitis (IC). Methods We prospectively enrolled 214 patients clinically diagnosed with IC, 125 non-IC patients who underwent video urodynamic studies and PST, and another 144 non-IC patients who underwent cystoscopic hydrodistention before transurethral surgery. The sensitivity, specificity, and positive and negative predictive values were calculated for the PST and glomerulations after cystoscopic hydrodistention. Results After cystoscopic hydrodistention, glomerulations developed in 211/214 (98.6%) IC patients and 61/144 (42.4%) of the non-IC patients including patients with stones (45/67, 67%), hematuria (2/5, 40%), and stress urinary incontinence (SUI) (6/17, 35%). When positive glomerulation was defined as grade 2 or more, the sensitivity was 61.7%. The PST was positive in 183/214 (85.5%) IC patients and 7/17 (41%) with hypersensitive bladder, 7/32 (22%) with detrusor overactivity, 5/27 (18%) with SUI, 2/21 (10%) with lower urinary tract symptoms, and 2/25 (8%) with bladder outlet obstruction. The PST had a sensitivity of 85.5% and a specificity of 81.6% for diagnosis of IC. IC patients with a positive PST had a significantly smaller urgency sensation capacity, smaller voided volume, and greater bladder pain score. Conclusions Both the PST and glomerulations after hydrodistention are sensitive indicators of IC, but the specificity of glomerulations in the diagnosis of IC is lower than that of the PST. A positive PST is associated with a more hypersensitive bladder and bladder pain, but not the grade of glomerulations in IC patients. Neither test provided 100% diagnostic accuracy for IC, we might select patients into different subgroups based on different PST and hydrodistention results, not for making a diagnosis of IC but for guidance of different treatments.

Efficacy and Adherence of Flexibly Adding on a Second Antimuscarinic Agent for Patients with Refractory Overactive Bladder

To evaluate the efficacy and adverse events (AE) of flexibly adding on oxybutynin ER in patients with overactive bladder (OAB) refractory to monotherapy with the first muscarinic antagonist.