Search Results (124)

Background: Fibromyalgia syndrome (FMS) is a complex condition with poorly understood pathophysiology, characterized by widespread pain and an increasing recognition of its associations with genitourinary symptoms. The objective of this study was to characterize the prevalence, phenotype, and common comorbidities of lower urinary tract symptoms (LUTS) in women with FMS. Methods: A retrospective observational study was conducted using electronic medical records of 440 women diagnosed with FMS at a single institution between 1 January 2018, and 1 January 2024. Study subjects were evaluated for diagnoses associated with LUTS, including interstitial cystitis (IC), overactive bladder (OAB), and stress urinary incontinence (SUI), alongside comorbidities such as irritable bowel syndrome (IBS), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Multivariate analyses were performed to assess predictors of conditions associated with LUTS. Results: LUTS were identified in 37.0% of FM patients. GAD and IBS were significantly associated with conditions associated with LUTS (OR = 4.62; OR = 8.53, p < 0.001). SUI was present in 17.05% of patients, falling between survey-based and confirmed prevalence rates in the general population. IC was diagnosed in 2.95% of FMS patients. OAB was observed in 6.8% of patients and associated with GAD (OR = 5.98, p < 0.001). Conclusions: This study highlights a substantial burden of diagnoses associated with LUTS in patients with FMS. There is relatively high prevalence of SUI and IC in this dataset. IBS and GAD were commonly found to co-occur with one or more LUTS-associated condition. Future prospective studies are needed to investigate a multimodal approach to the treatment of LUTS in these patients. Full article

Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75^NTR. The aim of the presented study was to assess whether p75^NTR antagonist THX-B can modulate LPS-mediated inflammation in bladder cells. In vitro expression and LPS-activation of p75^NTR were confirmed in urothelial (URO) and smooth muscle (SMC) cells. In UROs, p75^NTR antagonism abolished the LPS-elicited rise in membrane-bound and soluble TNF-α. However, it could not prevent LPS-induced rise in phosphorylated ERK nor decrease in phosphorylated p38MAPK, nor the increase in iNOS and nitric oxide (NO) content. On the other hand, in SMCs, LPS increased phosphorylation of JNK, nuclear translocation of NF-κB, and association of TRAF6 to p75^NTR, outcomes prevented by p75^NTR antagonism. In UROs, LPS decreased the expression of tight junction proteins, ZO-1 and occludin, with the latter rescued by p75^NTR antagonism. Intraurethral instillation of LPS increased inflammation in the lamina propria, activation of JNK, and contractile activity of bladder tissue. Alternatively, intraperitoneal THX-B injections prevented LPS-induced inflammation but not enhanced muscle contraction. Our results suggest that inhibition of p75^NTR could help in reducing bladder symptoms during cystitis. Full article

Interstitial cystitis/bladder pain syndrome (IC/BPS) causes significant discomfort in patients and impairs the quality of urination. Pterostilbene (PTE), a natural polyphenol antioxidant, has demonstrated beneficial effects in mitigating inflammation, enhancing antioxidant capacity, and ameliorating organ dysfunction in various chronic nonspecific inflammatory conditions. The aim of this study was to evaluate the efficacy of PTE in IC/BPS and elucidate its underlying mechanisms using a rat model of cyclophosphamide (CYP)-induced interstitial cystitis. In comparison, chronic pain progression, histopathological features, and cytokine levels demonstrated that PTE mitigated the severity of symptoms in CYP-induced rats by inhibiting the NLRP3 inflammasome in a dose-dependent manner. Further mechanistic investigations indicated that PTE intervention alleviated oxidative stress in CYP-induced IC in rats via activation of the Nrf2/HO-1 signaling pathway. Moreover, inhibitors of the Nrf2/HO-1 pathway effectively blocked PTE-mediated attenuation of oxidative stress. The suppression of NLRP3 inflammasome activation by PTE could also be reversed by inhibition of the Nrf2/HO-1 pathway. In vitro studies revealed that PTE enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and suppressed NLRP3 inflammasome activation in SV-HUC-1 cells exposed to lipopolysaccharide (LPS) and Adenosine Triphosphate (ATP). These findings collectively suggest that PTE treatment inhibits oxidative stress and suppresses NLRP3 inflammasome activation through modulation of the Nrf2/HO-1 pathway. Full article

Background/Objectives: Bladder pain syndrome (BPS), or painful bladder syndrome (PBS)/interstitial cystitis (IC), is a chronic inflammatory condition characterized by symptoms like pain, urgency, urinary incontinence, and sometimes urinary retention, which significantly affect patients’ quality of life. The etiology of PBS/IC remains unclear and may be multifactorial, with no definitive treatment currently available. The challenge lies in finding new therapeutic strategies. Various intravesical treatments, such as heparin, hyaluronic acid, and botulinum toxin, are commonly used for PBS/IC. In this study, we aimed to evaluate the anti-inflammatory effects of intravesical Vessilen^® (a new formulation consisting of 2% adelmidrol and 0.1% sodium hyaluronate) in patients with IC/PBS or other bladder disorders. Methods: This was a pilot study conducted at a tertiary-level urogynecology center. Two validated questionnaires were administered to patients before and after treatment: the Visual Analogue Scale (VAS) and the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS Long Form). The Patient Global Impression (PGI) scale was used to assess symptom severity. Results: Among the 25 patients who completed six weekly instillations, a significant decrease in bladder symptoms was observed, as indicated by both the ICIQ-FLUTS scale (89.3 vs. 61.3; p = 0.021) and VAS score (4.4 vs. 2.6; p < 0.001). Additionally, 80% of patients reported symptom improvement (PGI-I score ≤ 3). Conclusions: Intravesical Vessilen^® (adelmidrol + sodium hyaluronate) appears to be an innovative therapeutic approach for PBS/IC and other chronic inflammatory bladder disorders due to its anti-inflammatory and antinociceptive properties. Full article

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by persistent bladder-related pain and urinary symptoms, often refractory to conventional treatments. Sacral neuromodulation (SNM) has emerged as a promising therapeutic option for managing refractory IC/BPS. Methods: This retrospective study included 24 patients with IC/BPS treated with SNM between 2017 and 2022. Baseline and follow-up data were collected on pain, opioid use, urinary symptoms, and quality of life. Patients underwent a trial of tonic stimulation before permanent implantation. Continuous variables were reported as median (IQR) and categorical data as counts and percentages. Pre- and post-SNM differences were analyzed using the Wilcoxon rank-sum test. Kaplan–Meier analysis evaluated lead survival, and a Sankey diagram illustrated employment status transitions. Results: Patients had a median age of 54.5 years (IQR: 47–61), with 92% female. Subtypes included Type 1 IC/BPS (8.3%), Type 2 (45.8%), Type 3 (37.6%), and unknown type (8.3%). Median pain duration was 4.5 years (IQR: 3–7.3). SNM resulted in significant improvements in pain (NRS: baseline 8 [IQR: 8–9], last follow-up 3 [IQR: 2–4], p < 0.0001), opioid use (MME: baseline 20 [IQR: 10–40], last follow-up 0 [IQR: 0–10], p < 0.0001), urinary function (24-h voids: baseline 19 [IQR: 14.5–25.8], last follow-up 8 [IQR: 6–12], p < 0.0001), and quality of life (QOL) (EQ-5D-5L: baseline 0.50 [IQR: 0.36–0.56], last follow-up 0.83 [IQR: 0.76–0.89], p < 0.0001). Employment rates increased from 43.5% to 50%, and unemployment decreased from 8.7% to 4.2%. The median follow-up was 35 months (IQR: 28–53). Conclusions: SNM significantly improved pain, urinary symptoms, quality of life, and employment outcomes in patients with refractory IC/BPS. These findings highlight its efficacy as a minimally invasive and reversible option for managing this challenging condition. Full article

This study applied K-means cluster analysis to urinary biomarker profiles in interstitial cystitis/bladder pain syndrome (IC/BPS) patients, aiming to provide a new perspective on disease classification and its clinical relevance. We retrospectively analyzed urine samples from 127 IC/BPS patients and 30 controls. The urinary levels of 10 inflammatory cytokines and three oxidative stress markers (8-hydroxy-2-deoxyguanosin [8-OHdG], 8-isoprostane, and total antioxidant capacity [TAC]) were quantified. K-means clustering was performed to identify biomarker-based patient subgroups. IC/BPS patients exhibited significantly elevated urinary levels of Eotaxin, MCP-1, NGF, 8-OHdG, 8-isoprostane, and TAC compared to controls (all p < 0.05). K-means clustering identified four distinct subgroups. Cluster 4, characterized by the highest levels of inflammatory and oxidative stress biomarkers, comprised 85% ESSIC type 2 IC/BPS patients and exhibited the lowest visual analogue scale (VAS) pain scores and maximal bladder capacity (MBC). Correlation analysis revealed distinct cluster-specific associations between biomarker levels and clinical parameters, including the VAS pain score, MBC, the grade of glomerulation, and treatment outcomes. Applying K-means clustering to urinary inflammatory and oxidative stress biomarkers provides a new perspective on disease classification, identifying IC/BPS subtypes with distinct clinical and biochemical characteristics. This approach may refine disease phenotyping and guide personalized treatment strategies in the future. Full article

Chronic urinary tract infection (UTI) presents with protracted lower urinary tract symptoms and elevated urinary leukocyte counts, but its bacterial etiological agents remain obscure. In this cross-sectional investigation, we aimed to unravel the role of the bladder microbiota in chronic UTI pathogenesis by studying the host immune response. Urine samples were collected from healthy controls (HT), chronic UTI patients who had not initiated treatment (PT) and those undergoing treatment (OT), then sorted into white blood cell (WBC) and epithelial cell (EPC) fractions. Bacteria associated with both fractions were identified by chromogenic agar culture coupled with mass spectrometry and 16S rRNA sequencing. Distinct WBC-exclusive bacteria were observed in the healthy population, but this pattern was less obvious in patients, plausibly due to epithelial shedding and breaching of the urothelial barrier. We also described a bacterial fingerprint guided by Escherichia that was able to stratify patients based on symptom severity. Clustering analyses of mean rank changes revealed highly statistically significant upward and downward ecological shifts in communities of bacteria between the healthy and diseased populations. Interestingly, many of the most abundant genera identified in sequencing remained stable when compared between the study cohorts. We concluded that reshuffling of the urinary microbiome, rather than the activity of a single known urinary pathogen, could drive chronic UTI. Full article

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is mysterious and difficult to diagnose without cystoscopic hydrodistention. This study aimed to explore non-invasive and highly reliable urine biomarkers to identify Hunner’s IC (HIC) and different non-Hunner’s IC (NHIC) subtypes. Methods: In total, 422 women with and without clinically diagnosed IC/BPS (n = 376 and 46, respectively) were retrospectively enrolled. Patients were diagnosed with HIC or NHIC by cystoscopic hydrodistention under anesthesia. Then, the maximal bladder capacity (MBC) and glomerulation grade were determined. Thirteen urine inflammatory cytokines, chemokines, and oxidative stress biomarkers based on the previously reported predictors of IC/BPS were assayed using commercial microsphere kits. The dataset was randomly divided into training (70%) and test (30%) sets for model construction and validation using logistic regression and stepwise variable selection techniques. To construct the predictive models, univariate analysis was performed to evaluate the discriminative power of each urinary biomarker, measured by the area under the curve (AUC). Biomarkers with AUC values < 0.6 were excluded from further modeling. Multivariate logistic regression was then employed, with variables selected through stepwise forward selection based on log-likelihood criteria. For dichotomization, cutoff values were determined using quartile ranges from the control group. The final model’s performance was assessed using AUC, accuracy, sensitivity, and specificity in both training and test sets. Results: By setting the screening criterion to AUC ≥ 0.60, the potential urinary biomarkers for identifying IC/BPS cases were eotaxin, monocyte chemoattractant protein-1, tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoprostane. Those for identifying HIC from the IC/BPS cohort were interleukin (IL)-6, IL-8, interferon γ-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). A diagnostic algorithm using a cluster of urinary biomarkers included TNF-α ≥ 0.95 pg/mL or 8-OHDG ≥ 22.34 pg/mL and 8-isoprastane ≥ 22.34 pg/mL for identifying IC/BPS from the overall cohort; for identifying HIC from the IC/BPS cohort, the urinary IP-10 ≥ 3.74 pg/mL or IP-10 ≥ 19.94 pg/mL was added. Conclusions: Using a cluster of urinary biomarkers such as TNF-α or 8-OHdG and 8-isoprostane can identify IC/BPS from a study cohort, and adding the urinary IP-10 can distinguish HIC from IC/BPS cases. Full article

The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5′-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other’s mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders. Using an ex vivo murine detrusor-free bladder model to access the LP during bladder filling and a sensitive HPLC-FLD detection methodology, we evaluated the decrease in ATP and the increase in adenosine 5′-diphosphate (ADP), adenosine 5′-monophosphate (AMP), and adenosine by s-NTDs released in the LP. Endogenous PGE₂ increased the spontaneous but not the distention-induced release of s-NTD via EP2 and EP3 prostanoid receptors, whereas exogenous PGE₂ increased the spontaneous s-NTD release via EP3, EP4, and FP receptors and the distention-induced s-NTD release via EP1-4 and FP receptors. Endogenous PGF_2α, PGD₂, and PGI₂ did not change the s-NTD release. Exogenous PGD₂ increased the spontaneous s-NTD release via DP2 receptors and the distention-induced s-NTD release via DP1 and DP2 receptors. Exogenous PGF_2α increased the spontaneous but not the distention-induced release of s-NTD via FP receptors. It is possible that higher concentrations of PGE₂, PGF_2α, and PGD₂ (as expected in inflammation, bladder pain syndrome, or overactive bladder) potentiate the release of s-NTDs and the consecutive degradation of ATP as a safeguard mechanism to prevent the development of excessive bladder excitability and overactivity by high amounts of extracellular ATP. Full article

Background/Objectives. This study aimed to improve machine learning models for diagnosing interstitial cystitis/bladder pain syndrome (IC/BPS) by comparing classical machine learning methods with newer AutoML approaches, utilizing biomarker data and patient-reported outcomes as features. Methods. We applied various machine learning techniques to biomarker data from the previous IP4IC and ICRS studies to predict the presence of IC/BPS, a disorder impacting the urinary bladder. Data were sourced from two nationwide, crowd-sourced collections of urine samples involving 2009 participants. The models utilized included logistic regression, support vector machines, random forests, k-nearest neighbors, and AutoGluon. Results. Expanding the dataset for model training and evaluation resulted in improved performance metrics compared to previously published findings. The implementation of AutoML methods yielded enhancements in model accuracy over classical techniques. The top-performing models achieved a receiver-operating characteristic area under the curve (ROC-AUC) of up to 0.96. Conclusions. This research demonstrates an improvement in model performance relative to earlier studies, with the top model for binary classification incorporating objective urinary biomarker levels. These advancements represent a significant step toward developing a reliable classification model for the diagnosis of IC/BPS. Full article

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence of these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the prevalence of the comorbidity of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, and “bladder pain syndrome”. We performed a meta-analysis of the results. Results: The meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranged from 15.5% to 78.3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Prevalence data about the coexistence of endometriosis and IC/PBS are highly heterogeneous, probably due to the paucity of available data. However, in cases of endometriosis unresponsive to treatment, other reasons for CPP (such as IC/PBS) need to be ruled out. Full article

Lower urinary tract dysfunction (LUTD) was associated with bladder inflammation and tissue hypoxia with oxidative stress. The objective of the present study was to investigate the profiles of urine inflammatory and oxidative stress biomarkers in females with LUTD and to develop a urine biomarker-based decision tree model for the prediction. Urine samples were collected from 31 female patients with detrusor overactivity (DO), 45 with dysfunctional voiding (DV), and 114 with bladder pain syndrome (BPS). The targeted analytes included 15 inflammatory cytokines and 3 oxidative stress biomarkers (8-hydroxy-2-deoxyguanosin, 8-isoprostane, and total antioxidant capacity [TAC]). Different female LUTD groups had distinct urine inflammatory and oxidative stress biomarker profiles, including IL-1β, IL-2, IL-8, IL-10, eotaxin, CXCL10, MIP-1β, RANTES, TNFα, VEGF, NGF, BDNF, 8-isoprostane, and TAC. The urine biomarker-based decision tree, using IL-8, IL-10, CXCL10, TNFα, NGF, and BDNF as nodes, demonstrated an overall accuracy rate of 85.3%. The DO, DV, and BPS accuracy rates were 74.2%, 73.3%, and 93.0%, respectively. Internal validation revealed a similar overall accuracy rate. Random forest models supported the significance and importance of all selected nodes in this decision tree model. The inter-individual variations and the presence of extreme values in urine biomarker levels were the limitations of this study. In conclusion, urine inflammatory and oxidative stress biomarker profiles of different female LUTDs were different. This internally validated urine biomarker-based decision tree model predicted different female LUTDs with high accuracy. Full article

Several studies have shown interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition that poses challenges in both diagnosis and treatment, is associated with painful pelvic floor muscles (PFM) and altered neural drive to these muscles. However, its pathophysiology could also involve other alterations in the electrical activity of PFM motor units (MUs). Studying these alterations could provide novel insights into IC/BPS and help its clinical management. This study aimed to characterize PFM activity at the MU level in women with IC/BPS and pelvic floor myalgia using high-density surface electromyography (HD-sEMG). Signals were recorded from 15 patients and 15 healthy controls and decomposed into MU action potential (MUAP) spike trains. MUAP amplitude, firing rate, and magnitude-squared coherence between spike trains were compared across groups. Results showed that MUAPs had significantly lower amplitudes during contractions on the patients’ left PFM, and delta-band coherence was significantly higher at rest on their right PFM compared to controls. These findings suggest altered PFM tissue and neuromuscular control in women with IC/BPS and pelvic floor myalgia. Our results demonstrate that HD-sEMG can provide novel insights into IC/BPS-related PFM dysfunction and biomarkers that help identify subgroups of IC/BPS patients, which may aid their diagnosis and treatment. Full article

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient’s needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition. Full article

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner’s interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management. Full article