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.

Potential urine biomarkers in bladder outlet obstruction-related detrusor underactivity.

Detrusor underactivity (DU), an important but under-researched issue, is thought to be complex and multifactorial in etiology, pathophysiology, and diagnosis. Bladder outlet obstruction (BOO) is one of the important known etiologies of DU, with significant morphologic and physiologic changes of the urothelium, suburothelium, and detrusor muscle in the urinary bladder. Chronic urinary bladder ischemia and repeated cycles of ischemia and reperfusion injury cause excessive oxidative stress, and it is thought to be responsible for the development of DU. DU might be the late phase or decompensated status of BOO, with the possible mechanisms of afferent nervous dysfunction, increased inflammation, denervation of the detrusor muscle, and myogenic failure. Prostaglandin E2 (PGE2) involves in the physiological detrusor contraction, and might provide the prognostic value for the recoverability of DU. Neurotrophins, including nerve growth factor and brain-derived neurotrophic factor, involve in the neuroplastic changes in many inflammatory bladder diseases, including BOO and DU. Oxidative stress biomarkers, including 8-hydroxy-2-deoxyguanosine, F2-isoprostane, and the involved pro-inflammatory cytokines, have been applied in BOO due to their involvements in chronic bladder ischemia. PGE2, neurotrophins, inflammatory cytokines, and oxidative stress biomarkers are the potential urine biomarkers in BOO-related DU.

Xanthogranulomatous inflammation caused by K. pneumonia and nocardiosis mimicking a uterine tumor and invading the ureter and colon: A case report and review of the literature.

OBJECTIVE: To present a rare case of xanthogranulomatous inflammation (XI) mimicking a uterine sarcoma and invading the ureter and colon. CASE REPORT: A 66-year-old woman presented with lower abdominal pain. Pelvic examination showed tenderness over the lower abdominal region without cervical discharge. Per-rectal examination showed a hard tumor on the posterior uterine wall, while ultrasonography showed a tumor-like mass extending from the posterior uterine wall to the rectum. Magnetic resonance imaging showed signs of endometrial cancer invading the rectum. However, the tumor markers carbohydrate antigen (CA) 125, CA199, and carcinoembryonic antigen were in the normal range. Cystoscopy, panendoscopy, and colonoscopy showed no significant findings. On performing exploratory laparotomy, we observed pus and severe adhesion on the posterior uterine wall and rectum. Hysterectomy, bilateral adnexectomy, colectomy, and partial left ureter resection were performed. The final pathology showed XI. The pus culture revealed Klebsiella pneumonia and PCR revealed nocardiosis. The patient received 2 weeks of antibiotic treatment and was discharged thereafter. CONCLUSION: XI in elderly women is rare, and hence, differential diagnoses should be carefully considered.

Idiopathic Multicentric Castleman Disease with Strikingly Elevated IgG4 Concentration in the Serum and Abundant IgG4-Positive Cells in the Tissue: A Case Report.

Idiopathic multicentric Castleman disease (iMCD) can be challenging to distinguish clinically and histopathologically from Immunoglobulin G4-related disease (IgG4RD). A 73-year-old man was referred to a rheumatologist for suspected autoimmune-related polyclonal hypergammaglobulinemia. The patient had a history of multiple lymphadenopathies in the neck for over 20 years. Laboratory data showed elevated serum immunoglobulin G4 (IgG4) levels, hypergammaglobulinemia, high C-reactive protein (CRP) levels, marked anemia, and positivity for several autoantibodies. Additionally, imaging studies revealed multiple enlarged lymph nodes and multifocal, ill-defined, small patchy opacities over the lung. Biopsies of the neck lymph node and right lung revealed typical features of multicentric Castleman disease (MCD). Immunohistochemical staining was negative for human herpesvirus-8 (HHV-8) in both lymph nodes and the right lung, sub-classified as iMCD, whereas the IgG4/IgG ratio was >40%, which raised the suspicion of IgG4RD. However, serological cytokine analysis demonstrated an increased interleukin-6 (IL-6) level, alongside systemic inflammatory and histopathological features, distinguishing MCD from IgG4RD in this patient. The patient was treated with short-term glucocorticoids and regular infusion of an anti-IL-6 receptor monoclonal antibody (tocilizumab), with satisfactory clinical and radiographic responses. Notably, differentiating MCD from IgG4RD is crucial for optimal treatment. Clinical and pathological features may assist in distinguishing between these two diseases.

Pathogenesis evidence from human and animal models of detrusor underactivity.

Detrusor underactivity (DU) is a common urodynamic diagnosis in patients with lower urinary tract symptoms and large post-voiding residual volume. Animal and human studies showed the possible etiologies of DU include central or peripheral nerve injury, bladder outlet obstruction, chronic ischemia, aging, diabetes mellitus, and sympathetic inhibition of micturition reflex. Evidence from animal and human DU studies with various etiologies revealed highly similar gross and histological characteristics in the bladders, including increased bladder weight, bladder wall thickening, inflammation, collagen deposition, and fibrosis. In electron microscopy, smooth muscle destruction, swollen mitochondria, decreased nerve innervation, caveolae, and umbrella cell fusiform vesicles were noted in the DU bladders. Most animal DU models demonstrate detrusor contractility changes from compensatory to the decompensatory stage, and the change was compatible with human DU observation. The cystometry in the DU animal studies is characterized by impaired contractility, prolong intercontraction interval, and hyposensation, while in vitro bladder muscle strips experiment may exhibit normal detrusor contractility. Decreased bladder blood flow and increased oxidative stress in bladders had been proved in different animal DU models, suggesting they should be important in the DU pathogenesis pathway. Sensory receptors mRNA and protein expression changes in DU bladders had been observed in both animal and human studies, including muscarinic receptors M2, M3, adrenergic receptor ß3, purinergic receptor P2X1, P2X3, and transient receptor potential vanilloid (TRPV) 1 and TRPV4. Although some of the sensory receptors changes remain controversial, it might be the target for further pharmacologic treatments.

Clinical Correlation of Bladder Electron Microscopic Characteristics in Patients with Detrusor Underactivity of Various Etiologies.

This study aimed to investigate the ultrastructural characteristics of the bladder of patients with detrusor underactivity (DU) of various etiologies. Twenty-five patients with DU and control subjects underwent urodynamic testing and transmission electron microscopic examination of bladder specimens. The epithelium, lamina propria, and muscle layers were analyzed separately. The DU bladders exhibited total epithelial denudation (52%). In the bladders with remaining epithelium, apical cell uroplakins (44.4%) and tight junction complexes (77.8%) were also noted. The lamina propria was characterized by loose extracellular connective tissue (48%) and a lack of nerve terminals (76%). Smooth muscle shrinkage and a loss of their regular spindle shape (91.6%) were also noted in the detrusor layer. Patients with DU with intact epithelial cell layers had significantly larger void volumes and maximal flow rates than those with mild or severe epithelial denudation. Patients with remaining nerve terminals in lamina propria had a stronger first sensation of filling and smaller residual urine volume than those without nerve terminals. The proportion of ultrastructural defects of the bladder was not significantly different among patients with DU of various etiologies and treatment outcomes. DU bladders were characterized by ultrastructural defects in the entire bladder, and the defects were correlated to clinical parameters.

Diagnostic and prognostic value of urine biomarkers among women with dysfunctional voiding.

The current study aimed to investigate the diagnostic and prognostic value of urine biomarkers among female patients with dysfunctional voiding (DV). Urine samples were collected from 43 female patients with DV and 25 controls. Oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine [8-OHdG], 8-isoprostane, and total antioxidant capacity [TAC]) and inflammatory markers (interleukin-1 beta [IL-1ß], IL-2, IL-6, IL-8, tumor necrosis factor alpha, nerve growth factor, and brain-derived neurotrophic factor) levels were analyzed. In total, 26 patients with DV received further treatment with biofeedback pelvic floor muscle exercise or external urethral sphincter botulinum toxin A injections. Patients with DV had significantly higher urine 8-OHdG, IL-1ß, IL-8, and brain-derived neurotrophic factor levels than controls. Both urine 8-OHdG and IL-1ß levels were positively correlated with clinical symptoms. Patients with DV who had successful treatment outcomes had significantly lower pretreatment urine 8-isoprostane and TAC levels than those with unsuccessful outcomes. The pretreatment urine TAC level was the only independent predictor of successful treatment outcomes (odds ratio: 0.995). Compared with controls, female patients with DV had distinct urine oxidative stress biomarker and inflammatory marker profiles, which also mapped their clinical characteristics and treatment outcomes. These urine analytes might have diagnostic and prognostic values among female patients with DV.

Therapeutic Efficacy of Intravesical Platelet-Rich Plasma Injections for Interstitial Cystitis/Bladder Pain Syndrome-A Comparative Study of Different Injection Number, Additives and Concentrations.

Purpose: Intravesical platelet-rich plasma (PRP) injections have been demonstrated effective in relieving symptoms among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This study compared the clinical efficacy among different injection number, adding solution, and concentrations of PRP. Methods: A total of 63 patients with IC/BPS were enrolled and randomly allocated to four subgroups who received single high-dose PRP (from 100 ml whole blood) plus 10 ml of normal saline or plasma injected over 20 or 40 sites. Patients were followed up at 1, 3, and 6 months for changes in the IC symptom index (ICSI) and problem index (ICPI), visual analog scale (VAS), global response assessment (GRA), and urodynamic parameters. Furthermore, we compared the clinical outcome with our previous study in a group of 55 IC/BPS patients who underwent four monthly low-dose PRP (from 50 ml whole blood) injections. Results: The result of this study showed significant improvements in IC symptoms (ICSI 11.9 ± 4.4 vs. 10.2 ± 4.9, p = 0.009; ICPI 12.3 ± 3.4 vs. 10.6 ± 4.7, p = 0.003); VAS (5.46 ± 2.96 vs. 3.83 ± 3.1, p 0.000), and maximum flow rate (10.4 ± 4.9 vs. 17.1 ± 11.5 ml/s, p = 0.000) at 3 months after single high-dose PRP injection. However, no significant differences in therapeutic results were observed among subgroups, regardless of the added component or injecting site. The improvements of ICSI, ICPI, and GRA at 6 months were lower in comparison with the results of four low-dose PRP injections. All patients were free of dysuria, urinary retention, or urinary tract infection after PRP treatment. Conclusion: Intravesical PRP injection is effective for IC/BPS. The addition of normal saline or plasma and injection site had no influence on therapeutic efficacy. However, the symptom improvement and GRA after a single high-dose PRP injection was lower than that after four low-dose PRP injections 6 months after the first treatment. Limitation of the study is lack of sham control group.

Inflammation and Barrier Function Deficits in the Bladder Urothelium of Patients with Chronic Spinal Cord Injury and Recurrent Urinary Tract Infections.

Patients with spinal cord injury (SCI) commonly experience neurogenic voiding dysfunctions and urinary tract complications, including recurrent urinary tract infections (rUTI). The bladder mucosa barrier function contributes to UTI prevention. This study investigated changes in bladder urothelium protein expression in patients with SCI and rUTI. From June 2011 to November 2017, 23 patients (19 men and 4 women) with chronic SCI were enrolled (mean age: 43 years. Bladder tissues from 6 healthy adults served as the normal control group. Biopsy samples (9 partial cystectomies and 14 bladder biopsies) were analyzed for functional biomarkers using western blot and immunohistochemistry analysis. The barrier function proteins E-cadherin, zonula occludens 1 (ZO-1) and uroplakin III (UPK-3) were significantly reduced, whereas tumor protein p63 (TP63) was significantly increased in SCI patients compared with controls. No significant differences in basal cell progenitor proteins were observed between groups. The proliferation marker Ki-67, the proapoptotic marker BCL-2-associated X protein (BAX), and proinflammatory proteins were increased in patients with SCI compared with controls. No significant differences were observed between SCI patients with and without recently rUTI. These results suggest that SCI patients experience chronic bladder inflammation, increased apoptosis, and reduced barrier function, contributing to rUTI.

Improved Urothelial Cell Proliferation, Cytoskeleton and Barrier Function Protein Expression in the Patients With Interstitial Cystitis/Bladder Pain Syndrome After Intravesical Platelet-Rich Plasma Injection.

PURPOSE: To investigate urothelial cell proliferation, cytoskeleton, inflammation, and barrier function protein expressions in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) after intravesical platelet-rich plasma (PRP) injections. METHODS: A total of 19 patients with IC/BPS underwent 4 monthly intravesical PRP injections. Bladder biopsies were taken at the first and fourth PRP treatment. The bladder specimens were analyzed using the Western blot and immunochemical staining for progenitor cell markers for sonic hedgehog (Shh), CD34, and cytoskeleton proteins cytokeratin 5 (CK5), CK14, CK20; barrier function markers for zonula occludens-1 (ZO-1), E-cadherin, and intercellular adhesive molecule-1, tryptase and transforming growth factor-ß (TGF-ß). Global response assessment (GRA) was used to evaluate treatment outcomes. RESULTS: The mean age of patients was 55.6 years. After PRP injections, the functional bladder capacity and maximum flow rate increased, and the visual analogue scale (VAS) of pain, interstitial cystitis (IC) symptom index, IC problem index, O'Leary-Sant symptom score, and GRA improved in all patients. Urothelium Shh, CK5, ZO-1, E-cadherin, and TGF-ß expressions increased significantly after repeated PRP injections. By subgrouping, according to PRP treatment outcomes, significant increases in Shh, E-cadherin, and ZO-1 expressions were noted only in patients with GRA ≥1 or improved VAS, but not in patients with GRA=0 and no improvement in VAS. CONCLUSION: The level of urothelial barrier function protein and cell proliferation protein expression in the patients with IC/BPS was increased after repeat intravesical PRP injections. Intravesical repeat PRP injections may have potential to improve urothelial health and result in symptoms improvement in the patients with IC/BPS.

Ultrastructural changes in the underactive bladder.

Underactive bladder (UAB) is a symptom complex suggestive of detrusor underactivity (DU). Although it implies a primary dysfunction of the detrusor muscle, many other conditions such as advanced age, neurogenic factors, and bladder outlet obstruction also lead to UAB. The current understanding of the pathophysiology directly leading to UAB is limited. We believe that by identifying the morphological changes associated with UAB might shed light on this. Therefore, we searched literature with keywords of electron microscopy, ultrastructure, UAB, and DU to review current ultrastructural evidence concerning UAB.

Possible Association between Bladder Wall Morphological Changes on Computed Tomography and Bladder-Centered Interstitial Cystitis/Bladder Pain Syndrome.

This study aimed to evaluate the clinical significance of urinary bladder wall thickening on computed tomography (CT) among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS were prospectively enrolled and classified into three groups according to bladder CT finding: smooth bladder wall, focal bladder thickening, and diffuse bladder thickening. Among the 100 patients with IC/BPS, 49, 36, and 15 had smooth bladder wall, focal bladder thickening, and diffuse bladder thickening on CT, respectively. Patients with Hunner's lesion showed a higher proportion of diffuse and focal bladder thickening compared to those without the same (p < 0.001). Patients with diffuse bladder thickening displayed smaller first sensation of filling, cystometric bladder capacity, and voided volume compared to the rest (all p < 0.001). Patients with focal and diffuse thickening had a higher proportion of inflammatory cell infiltration, uroepithelial cell denudation, and granulation tissue compared to those with smooth bladder wall (p = 0.045, 0.002, and 0.005, respectively). Bladder wall thickening on CT was correlated with clinical phenotypes of IC/BPS, including histopathological findings. Focal or diffuse bladder wall thickening on CT might indicate the presence of chronic bladder wall inflammation and fibrosis and could be used to differentiate bladder-centered IC/BPS.

Difference in electron microscopic findings among interstitial cystitis/bladder pain syndrome with distinct clinical and cystoscopic characteristics.

Urothelial dysfunction may be a key pathomechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS). We therefore examined if clinical severity is associated with the extent of urothelial damage as revealed by electron microscopic (EM) analysis of biopsy tissue. One hundred IC/BPS patients were enrolled and 24 patients with stress urinary incontinence served as controls. Clinical symptoms were evaluated by visual analog scale pain score and O'Leary-Sant Symptom score. Bladder biopsies were obtained following cystoscopic hydrodistention. The presence of Hunner's lesions and glomerulation grade after hydrodistention were recorded and patients classified as Hunner-type IC (HIC) or non-Hunner-type IC (NHIC). HIC patients exhibited more severe defects in urothelium cell layers, including greater loss of umbrella cells, umbrella cell surface uroplakin plaque, and tight junctions between adjacent umbrella cells, compared to control and NHIC groups (all p < 0.05). Both NHIC and HIC groups demonstrated more severe lamina propria inflammatory cell infiltration than controls (p = 0.011, p < 0.001, respectively). O'Leary-Sant Symptom scores were significantly higher among patients with more severe urothelial defects (p = 0.030). Thus, urothelium cell layer defects on EM are associated with greater clinical symptom severity.

Acute Myeloid Leukemia Transformation from Myelofibrosis Upon Remission of an Orbital Myeloid Sarcoma - A Case Report.

PURPOSE: To report a case of an orbital myeloid sarcoma concurrent with JAK2 mutation myelofibrosis, which rapidly transformed into acute myeloid leukemia upon aggressive treatment. RESULTS: A 51-year-old woman had progressive swelling of periorbita for one month. Magnetic resonance imaging demonstrated a well-defined, mild enhanced mass indenting the adjacent right lateral rectus muscle and the globe. Biopsy from anterior orbitotomy revealed an orbital myeloid sarcoma. Bone marrow study showed concurrent myelofibrosis. Although the orbital lesion subsided remarkably under aggressive chemotherapy and radiotherapy, the leukemic transformation was noticed in the third month following the initial presentation. CONCLUSION: This case demonstrated that myeloid sarcoma should be included in the differential diagnosis of orbital diseases, with or without involvement of hematological disorders. Early diagnosis and aggressive treatment as for AML are crucial as the prognosis is usually poor for adult orbital MS.

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.

Sorafenib combined with dasatinib therapy inhibits cell viability, migration, and angiogenesis synergistically in hepatocellular carcinoma.

PURPOSE: Sorafenib is a multikinase inhibitor used for treatment of advanced hepatocellular carcinoma. Sorafenib resistance may be related to Src-induced cell migration and angiogenesis, which are regulated by cancer stem cell activation and release of vascular endothelial growth factor. Dasatinib is a Src inhibitor that inhibits Src phosphorylation and suppresses Src-associated cell migration and angiogenesis. This study investigated whether combined treatment with dasatinib can overcome sorafenib resistance. METHODS: Hepatoma cell lines were used for sorafenib and/or dasatinib treatment. Cell viability, cell migration, molecular expressions, and release of vascular endothelial growth factor by hepatoma cells were evaluated. Hepatoma cell culture medium was applied on human umbilical vein endothelial cells to monitor angiogenesis promoted by the hepatoma cells. RESULTS: Sorafenib and dasatinib combined therapy suppressed cell viability of hepatoma cells synergistically. Dasatinib suppressed sorafenib-induced cell migration via inhibiting sorafenib-induced Src/FAK phosphorylation, cell-to-cell contact and cancer stem cell activation. Culture medium from Chang liver and PLC/PRF/5 cells suppressed angiogenesis of human umbilical vein endothelial cells with any treatment, whereas sorafenib-treated medium of HepG2 cells induced angiogenesis. This sorafenib-induced angiogenesis was then suppressed by dasatinib. Vascular endothelial growth factor released from hepatoma cells was also inhibited by combined treatment. CONCLUSION: Src/FAK phosphorylation and cancer stem cell activation inducing cell migration and angiogenesis may be the key factors of sorafenib resistance. Sorafenib and dasatinib combined treatment suppresses cell migration and angiogenesis by inhibiting the Src/FAK phosphorylation, cell-to-cell contact, cancer stem cell activation, and release of vascular endothelial growth factor.

Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4.

Stronger contractility and smaller bladder capacity are common symptoms in ketamine cystitis (KC). This study investigates the association between expression levels of transient receptor potential cation channel subfamily V (TRPV) proteins and the clinical characteristics of KC. Bladder tissues were obtained from 24 patients with KC and four asymptomatic control subjects. Video urodynamic parameters were obtained before surgical procedures. The TRPV proteins were investigated by immunoblotting, immunofluorescence staining, and immunohistochemistry. The Pearson test was used to associate the expression levels of TRPV proteins with clinical characteristics of KC. The expression level of TRPV1 and TRPV4 was significantly higher in the severe KC bladders than in mild KC or control bladders. The TRPV1 proteins were localized in all urothelial cell layers, and TRPV4 was located in the basal cells and lamina propria. The expression of TRPV1 was negatively associated with maximal bladder capacity (r = - 0.66, P = 0.01). The expression of TRPV4 was positively associated with the velocity of detrusor pressure rise to the maximum flow rate (r = 0.53, P = 0.01). These observations suggest smaller bladder capacity and stronger contractility in KC are associated with an elevated expression of TRPV1 and TRPV4, respectively.

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.