Search

Pain that occurs during sexual activity is highly prevalent during a woman's lifetime, affecting ∼15% of women. The etiology of dyspareunia is multifactorial. Therefore, treatment must be individualized. This paper reviews the evaluation and treatment of the several common causes of dyspareunia and/or pelvic pain, including hormonally associated vestibulodynia, inflammation-associated vestibulodynia, neuroproliferative vestibulodynia, overactive pelvic floor muscle dysfunction, vulvar dysesthesia, persistent genital arousal disorder, and painful bladder syndrome. [ABSTRACT FROM AUTHOR]

Background: Intravesical application of birth tissue has been reported to inhibit inflammation, alleviate collagen fiber accumulation, and enhance bladder tissue generation. We have previously reported that intra-detrusor micronized amnion monolayer (AM) injections provide short-term clinical improvement in refractory IC/BPS patients. Herein, we evaluate the therapeutic responses and adverse events of micronized amnion/chorion bilayer (AC) in patients with refractory IC/BPS with 6 months follow-up. Methods: Fifteen patients affected by IC/BPS who failed conventional therapy received 100 mg of reconstituted micronized AC was injected intra-detrusor via cystoscopy under general anesthesia, using a 23-gauge needle. Twenty 0.5-mL injections were administered into the lateral and posterior bladder walls, avoiding the dome and trigone. Changes in interstitial cystitis symptom index (ICSI), Interstitial cystitis problem index (ICPI), Bladder pain/ interstitial cystitis symptom score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB), from baseline to 6 months post-injection were evaluated retrospectively. The safety of injections was analyzed. Results: Fifteen total refractory IC/BPS patients with an average age of 41.1 ± 14.5 years were included in the study, receiving intra-detrusor injections of 100 mg of micronized AC. One month after injections, significant improvement in IC/BPS symptom scores was noted in all patients. All patients maintained a sustained clinical response at 6 months post-injection. No product-related adverse events were observed. Conclusion: Our findings indicate that the AC formulation significantly reduces time to symptom relief in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS) and maintains a sustained response up to 6 months post-injection. These results suggest a promising clinical benefit of using an amnion/chorion bilayer product for treating IC/BPS. Further research is needed to confirm these findings and assess the long-term durability of this treatment approach. This study represents the first evidence supporting the clinical advantages of an amnion/chorion bilayer product in managing IC/BPS. [ABSTRACT FROM AUTHOR]

Disruption of the glycosaminoglycan (GAG)-layer and urothelial barrier is an important aspect of the pathophysiology of bladder pain syndrome/ interstitial cystitis. Intravesical hyaluronic acid (HA) is often used in treatments for IC/BPS, however the role in the urothelial barrier is unknown. This study aims to clarify the location and functional contribution of HA in the urothelium, using an in vitro model. Immunohistochemistry was performed on human and porcine biopsies and on porcine cell cultures to evaluate the location of HA. Functional contribution was assessed through transepithelial electrical resistance measurements and the effects on gene expression in a differentiated primary porcine urothelial cell model. HA was found throughout in the urothelium and most abundant around the basal layer. Digestion of HA increased impermeability of the urothelium, contrasting with the effect of protamine sulfate (PS). After HA digestion, quantitative PCR analysis revealed upregulation of HA-synthesizing gene (HAS3) and the inflammatory marker (IL8). Treatment with HA and/or chondroitin sulfate therapy in undamaged cells upregulated genes related to GAG synthesis, barrier markers and inflammation. In PS-damaged cells, GAG therapy only upregulated genes associated with HA synthesis and inflammation, without affecting barrier recovery speed. These results emphasize the interaction of HA on urothelial cell inflammation and barrier repair physiology. HA seems to not directly restore the urothelial luminal GAG layer but influences barrier integrity through its interactions with urothelial cells. [ABSTRACT FROM AUTHOR]

Background: Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and vulvodynia often coexist, exacerbating patient symptoms and complicating the diagnosis and treatment. This study aimed to identify distinct subtypes within a BPS/IC and vulvodynia cohort and evaluate their symptom profiles, psychological characteristics, and sexual function indicators. Methods: A cross-sectional analysis was conducted on 150 female patients diagnosed with BPS/IC and vulvodynia. The patients completed validated questionnaires assessing bladder symptoms, psychological distress (PHQ-9 and GAD-7), and sexual function (FSFI and FSDS-R). Hierarchical and K-means clustering were used to identify patient subgroups. Results: Three distinct clusters were identified. Cluster 1 exhibited moderate bladder-specific symptoms and psychological distress. Cluster 2 had severe bladder symptoms and the highest psychological distress. Cluster 3, defined as the vulvodynia-predominant subtype, featured severe vulvodynia, significant psychological distress, and minimal bladder symptoms, aligning with a non-urologic pelvic pain phenotype. Sexual function was significantly impaired across all clusters, with Cluster 3 showing the most severe dysfunction. Conclusions: This study highlights the heterogeneity within BPS/IC and vulvodynia populations. The identification of a vulvodynia-predominant subtype and non-urologic pelvic pain phenotype emphasizes the need for personalized treatment strategies addressing both physical and psychological factors, particularly sexual dysfunction and psychological distress. [ABSTRACT FROM AUTHOR]

Interstitial cystitis is a fierce syndrome affecting the quality of life of thousands of individuals around the globe. It causes immense pain in the bladder and associated viscera along with inflammation-like lesions. The current medicinal and pharmacological research focuses on the protective and curative effects of phytochemicals in several ailments. Phytochemicals derived from many medicinal plants have shown potent outcomes in protection against various pathological conditions including interstitial cystitis. This review has summarized the insights of in vitro and in vivo studies regarding the effects of phytochemicals in fading the inflammation in bladder tissue and exhibiting a protective effect on the urothelium. Hemorrhagic cystitis is a common manifestation in patients undergoing chemotherapy with cyclophosphamide and related alkylating agents. Sodium 2-mercaptoethane sulfonate (Mesna) has traditionally been employed in clinical practice to counter cyclophosphamide-induced cystitis in humans. However, cyclophosphamide has been employed in developing animal models of interstitial cystitis in in vivo studies. Phytochemicals including quercetin, beta-caryophyllene, curcumol, boswellic acid, caftaric acid, some flavonoids and other secondary metabolites being a consequential component of numerous medicinal plants, have displayed a significant reduction in the levels of proinflammatory cytokines including TNF-α, NFĸB, IL-1β, NLRP3 inflammasome, IL-6, IL-2, matrix metalloproteinases etc. Uroprotective outcomes of these phytochemicals have been found to result in diminished oxidative stress and restoration of glutathione, superoxide dismutase, and related proteins in the inflamed bladder tissue. Many in vivo studies involving cyclophosphamide-induced interstitial cystitis have confirmed these findings. The coupling of phytotherapy with novel drug delivery systems such as nanoparticles, liposomes, nanotubes, quantum dots, etc. can help translate these beneficial effects of phytochemicals into clinical practice. Further investigations of these phytochemicals can provide intuition regarding the development of newer drug molecules having exclusive activity for attenuating interstitial cystitis. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have reported an increased risk of bladder cancer (BC) in IC/BPS patients. In this study, we re-examined the BC risk in a population based IC/BPS cohort to assess the potential detection bias caused by some IC/BPS patients diagnosed who might already have co-existing BC. Methods: We performed a retrospective cohort study based on a Research Database by extracting IC/BPS patients diagnosed within years 2002–2013. The patients in the study cohorts were identified based on at least 2 IC/BPS diagnoses and excluded patients with BC occurred before IC/BPS diagnosis. The primary outcome was BC events detected. Propensity scores (PSs) were calculated for matching IC/BPS cohort with non-IC/BPS cohort on a 1:1 basis. Cox proportional hazard regression analysis was then used to compare hazard ratios of BC development between 2 cohorts. Results: By excluding patients with BC diagnosed within 1 year after IC/BPS diagnosis, the study cohort was insignificantly different from the PS-matched control (Model 1, p = 0.219) but significantly different from the non-PS-matched control (Model 2, p < 0.001). However, when including patients with BC diagnosed within 1 year after IC/BPS diagnosis, the study cohort was significantly different from both PS-matched (Model 3, p = 0.002) and non-PS-matched (Model 4, p < 0.001) controls, indicating that excluding patients with BC diagnosed within 1 year after IC/BPS diagnosis and adopting PS matching method greatly reduce the BC detection bias. Conclusions: IC/BPS is not associated with BC. The detection bias of previous studies may result from inadequate recruitments of study cohorts or improper matching of control cohorts. [ABSTRACT FROM AUTHOR]

Purpose of Review: We intend to establish broad clinical subgroups of patients and match them to a more tailored approach with improved clinical outcomes. Recent Findings: Patient experience over the past four decades and investigative initiatives such as The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) have led to the development of four broad categories of IC/BPS patients: bladder-centric (which is further sub-divided into those with Hunner lesion disease (HLD) and those without (IC/BPS)); widespread/centralized pain; and myofascial pelvic floor tenderness. Other systems of patient categorization, such as UPOINT, now INPUT, highlight the complexities of patient assessment. Reanalysis of previous failed clinical trials and common sense suggests that matching the therapy's mechanism of action to the patient's phenotype may yield better therapeutic outcomes. Summary: Although the IC/BPS population is known to be phenotypically heterogeneous, therapeutic approaches afforded by most current guidelines have been relatively rigid, only accounting for those patients with and without Hunner lesions. Segregating the IC/BPS population further into distinct phenotypic groups that may respond to targeted therapy is relatively simplistic but represents an essential first step toward precision care. [ABSTRACT FROM AUTHOR]

Background: The etiology of interstitial cystitis/painful bladder syndrome (IC/BPS) remains elusive, presenting significant challenges in both diagnosis and treatment. To address these challenges, we employed a comprehensive approach aimed at identifying diagnostic biomarkers that could facilitate the assessment of immune status in individuals with IC/BPS. Methods: Transcriptome data from IC/BPS patients were sourced from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) crucial for gene set enrichment analysis. Key genes within the module were revealed using weighted gene co-expression network analysis (WGCNA). Hub genes in IC/BPS patients were identified through the application of three distinct machine-learning algorithms. Additionally, the inflammatory status and immune landscape of IC/BPS patients were evaluated using the ssGSEA algorithm. The expression and biological functions of key genes in IC/BPS were further validated through in vitro experiments. Results: A total of 87 DEGs were identified, comprising 43 up-regulated and 44 down-regulated genes. The integration of predictions from the three machine-learning algorithms highlighted three pivotal genes: PLAC8 (AUC: 0.887), S100A8 (AUC: 0.818), and PPBP (AUC: 0.871). Analysis of IC/BPS tissue samples confirmed elevated PLAC8 expression and the presence of immune cell markers in the validation cohorts. Moreover, PLAC8 overexpression was found to promote the proliferation of urothelial cells without affecting their migratory ability by inhibiting the Akt/mTOR/PI3K signaling pathway. Conclusions: Our study identifies potential diagnostic candidate genes and reveals the complex immune landscape associated with IC/BPS. Among them, PLAC8 is a promising diagnostic biomarker that modulates the immune response in patients with IC/BPS, which provides new insights into the future diagnosis of IC/BPS. [ABSTRACT FROM AUTHOR]

Purpose: The classification of different phenotypes of interstitial cystitis/ bladder pain syndrome (IC/BPS) provides different pathophysiology and associated treatment strategies. Most clinical studies have focused on bladder symptoms and cystoscopic findings. This study analyzed bladder wall thickness (BWT) and compared bladder conditions, urinary biomarkers, and histopathology among patients of IC/BPS with different BWT. Methods: A total of 182 patients with cystoscopy-proven IC/BPS underwent abdominal computed tomography (CT) before intervention. The BWT on CT was classified as smooth, focal thickness, and diffuse thickness. Clinical symptoms, urodynamic findings, cystoscopic characteristics, presence of Hunner's lesion, urinary biomarkers, and bladder histopathology were compared among the three subgroups. Results: Among the patients, 85 had smooth, 64 had focal, and 33 had diffuse BWT. There was a significant trend of patients with focal and diffuse BWT being significantly older with higher symptom scores, smaller bladder capacity, higher grade of glomerulations, and incidence of Hunner's IC. Pathological findings revealed that patients with diffused BWT, followed by those with focal thickness, had the greatest uroepithelial cell denudation and plasma cell infiltration. Patients with diffuse BWT has higher rate of inflammatory cell infiltration, nerve bundle hyperplasia, and granulation tissue. The urinary levels of tumor necrosis factor-alpha and oxidative stress biomarkers in IC/BPS patients with different BWT were significantly higher than those in the controls. Conclusion: BWT in CT scans can reflect chronic inflammation of the bladder wall in patients with IC/BPS, which is clinically relevant for the diagnosis and treatment of IC subtypes. [ABSTRACT FROM AUTHOR]

Female bladder pain syndrome (FBPS), previously known as interstitial cystitis/bladder pain syndrome, is a life-altering and morbid condition that occurs primarily in female patients and can be variable in presentation. Given the absence of pathognomonic symptoms and sensitive diagnostic tests, significant symptomatic overlap with numerous other pelvic conditions (such as pelvic floor tension myalgia or endometriosis) occurring in women makes diagnosis of FBPS challenging. The frequent co-occurrence of FBPS with other pain conditions and functional somatic syndromes further complicates diagnosis and management. The challenges have limited the progress made in understanding the pathophysiology of the condition and improving approaches to treatment and prevention. Improvement in standardization of the terminology used to describe this unique condition is needed to improve the accuracy of diagnosis and the clinical care for affected patients. Given the variability in presentation and the differing definitions for the condition world-wide, the American Urogynecologic Society and the International Urogynecologic Association convened a joint writing group to standardize terminology around common signs and symptoms of the condition and to clarify the diagnosis as it pertains to female patients with the condition. After careful consideration of a broad range of available data and clinical experiences, consensus opinion recommended adopting the term "FBPS" instead of the misleading "interstitial cystitis" to describe a chronic, intermittent condition of at least 3 months' duration affecting women involving symptoms of pain or discomfort localized to the bladder, often with bladder filling, which are not attributed to other pathology. This term will allow clinicians, researchers, and learners alike to standardize their understanding of FBPS. [ABSTRACT FROM AUTHOR]

The addition of meditation and yoga to standard interstitial cystitis/bladder pain syndrome care improved treatment response, decreased symptoms, and decreased treatment escalation. OBJECTIVE: To investigate whether yoga and meditation added to usual care improves treatment response in women with interstitial cystitis–bladder pain syndrome. METHODS: This randomized trial compared women with interstitial cystitis–bladder pain syndrome receiving standard care alone (control group) with those receiving standard care plus meditation and yoga (mind–body group). Standard care was defined as behavioral changes or medications recommended by the American Urological Association. Individuals in the control group received standard care, and those in the mind–body group received standard care augmented with a commercially available meditation application and standardized yoga tutorial video. Both groups continued their current interstitial cystitis–bladder pain syndrome standard care treatments. The primary outcome was the modified GRA (Global Response Assessment), comparing responders (moderately, markedly improved) with nonresponders at 12 weeks. On power analysis assuming α=5% and β=80%, a sample size of 82 participants was required to find 30% difference on the GRA between groups. Weekly GRA scores over 12 weeks were also compared. Secondary outcomes included ICPI (Interstitial Cystitis Problem Index)/ICSI (Interstitial Cystitis Symptom Index), pain, pain interference, anxiety/depression, and self-efficacy scores and treatment escalation over 12 weeks. RESULTS: Among 97 randomized participants (49 mind–body group, 48 control group), groups did not differ in characteristics or symptoms at baseline. The mind–body group had more GRA responders compared with the control group at 12 weeks (31/43 [72.1%] vs 10/39 [25.6%], relative risk [RR] 2.8, 95% CI, 1.6–4.6), corroborated by superior weekly GRA results over 12 weeks. The mind–body group had superior beneficial change on the ICPI (RR 1.8, 95% CI, 0.5–3.1), ICSI (RR 1.9, 95% CI, 0.2–3.6), and pain (RR 1.4, 95% CI, 0.4–2.5) scores than the control group at 12 weeks. The mind–body group required less treatment escalation than the control group (2/45 [4.4%] vs 14/42 [33.3%], RR 0.13, 95% CI, 0.03–0.55). CONCLUSION: The addition of meditation and yoga to standard interstitial cystitis–bladder pain syndrome care was associated with improved treatment response and required fewer additional interventions compared with standard care alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04820855. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chemical modification of naturally derived glycosaminoglycans (GAGs) expands their potential utility for applications in soft tissue repair and regenerative medicine. Here we report the preparation of a novel crosslinked chondroitin sulfate (~200 to 2000 kilodaltons) that is both soluble in aqueous solution and microfilterable. We refer to these materials as "SuperGAGs." One can further conjugate these materials with diverse capture agents to further modify polymer properties and add new capabilities. A representative material (GLX-100) demonstrated durable restoration of bladder impermeability in a gold standard animal model of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). Histologic examination of the animal bladders treated with a GLX-100 SuperGAG conjugated to biotin as a reporter demonstrated that the residence time of GLX-100 is superior to chondroitin sulfate (a product that is currently used for clinical treatment of patients with IC/BPS). As expected, this novel crosslinked GAG biopolymer was restricted to the luminal surface of the bladder wall. In this communication we describe a simple and versatile synthesis of a crosslinked glycosaminoglycan (GAG) biopolymer for soft tissue repair. Chondroitin sulfate (~12 kD) was crosslinked to form a water soluble and microfilterable polymer with approximately 200 to 2000 kD molecular weight. The synthesis presented here allows for control of molecular weight while avoiding formation of an extended block gel. Moreover, the procedure enables further chemical modification of the SuperGAG through the selection of a capture agent. A set of agents have been used, demonstrating the preparation of a family of SuperGAGs with diverse capabilities. We can optimize polymer properties, adjust adherence to various tissues, add reporters, and engage the biochemistry of surrounding tissues with peptides and other bioactives. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate prevalence and incidence rates of pigmentary maculopathy and retinopathy (PM/PR), and visual acuity (VA) changes in patients exposed to pentosan polysulfate sodium (PPS) and in patients with interstitial cystitis (IC) not exposed to PPS. Methods: This is a retrospective cohort study (January 2015–March 2021) which included adult de-identified patients from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) and Komodo Health database. Three patient cohorts were identified: two PPS-exposed patient cohorts, and Non-PPS-exposed IC patient cohort. Key study outcomes included PM/PR/Any (defined based on prior literature regardless of PPS exposure) and PM/PR/PPS (further defined by an algorithm that was based on clinical notes and other protocol-prespecified criteria in PPS-exposed patients), and VA changes in each respective cohort. Results: Prevalence of PM/PR/Any was relatively common in patients prior to PPS exposure (4.16%–8.43%). Incidence rate of PM/PR/PPS was uncommon in both PPS-exposed cohorts (0.13–0.15 per 100 person-years). Crude incidence rates of PM/PR/Any (based on ITT analysis) varied slightly across 3 study cohorts (2.13–2.81 and 2.38 per 100-person-years for PPS-exposed cohorts and Non-PPS-exposed IC cohort, respectively). Across all 3 study cohorts, patients with PM/PR/Any appeared to have approximately 2-fold higher proportion of 3 lines of VA worsening than those without PM/PR/Any. Conclusion: Prevalence of PM/PR was common in patients prior to PPS exposure. Incidence of PM/PR/PPS that may be associated with PPS exposure was relatively uncommon. Crude incidence rates of PM/PR appeared similar across all patient cohorts regardless of PPS exposure. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target. Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry. An in vitro HIC model was established using LPS-induced SV-HUC1 cells. PACAP knockdown was performed using siRNA. The expression of inflammatory markers (IL-6, IL-1β, TNF-α) and fibrotic markers (fibronectin 1, TGF-β1, collagen I) was evaluated via qPCR, Western blot, and ELISA. Cell migration and proliferation were analyzed using wound healing and CCK-8 assays. Transcriptomic profiling was conducted to identify differentially expressed genes (DEGs) and explore their functional significance. Results: PACAP expression was significantly elevated in the bladder tissues of HIC patients. LPS stimulation of SV-HUC1 cells induced PACAP expression alongside increased levels of inflammatory cytokines, validating the inflammatory model. PACAP knockdown markedly suppressed IL-6, IL-1β, and TNF-α expression and attenuated LPS-induced fibrosis by reducing fibronectin 1, TGF-β1, and collagen I levels. Additionally, PACAP knockdown inhibited LPS-induced cell migration and proliferation, as evidenced by wound healing and CCK-8 assays. Transcriptomic analysis revealed distinct molecular alterations in HIC tissues, including PACAP upregulation, implicating it in HIC pathogenesis. Conclusion: PACAP plays a pivotal role in the inflammatory and fibrotic pathways of HIC. PACAP knockdown alleviates LPS-induced pathological responses, highlighting its potential as a novel therapeutic target. Further research is warranted to investigate PACAP's precise mechanisms in HIC and its translational application in clinical settings. [ABSTRACT FROM AUTHOR]

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 PGF2α, 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 PGF2α increased the spontaneous but not the distention-induced release of s-NTD via FP receptors. It is possible that higher concentrations of PGE2, PGF2α, 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. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the classification systems for male chronic pelvic pain (CPP). Methods: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), and Web of Science were searched. Any publication, with no restriction to publication date, was eligible. Publications had to propose a classification system for CPP in males or provide additional information of a system that had been identified. Systems were assessed with an adapted Critical Appraisal of Classification Systems tool. Results: A total of 33 relevant publications were identified, with 22 proposing an original classification system. Systems aimed to: (i) diagnose CPP and/or differentially diagnose CPP from other conditions, (ii) differentially diagnose subtypes within CPP, or (iii) identify features that could inform underlying mechanisms and/or treatment selection. Conditions referred to as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome were most represented. Clinical signs/symptoms, pathoanatomical investigations, and presumed pain mechanisms were used for classification. Quality of systems was low to moderate, implying limitations to consider for their interpretation. Conclusions: Many classification systems for CPP in males exist. Careful consideration of their intended purpose is required. Future work should examine whether outcomes for patients are improved when decisions are guided by their use. [ABSTRACT FROM AUTHOR]

Purpose: Although the mechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, oxidative stress is suggested to be implicated in IC/BPS development. Sea buckthorn (SB; Hippophae rhamnoides L.) contains several compounds with antioxidant properties. In addition, intravesical application of hydrochloric acid (HCl) in rats induces histological changes similar to those observed in humans with IC. Therefore, the aim of this study was to evaluate the anti-inflammatory effects of SB in an HCl-induced rat cystitis model. Materials and Methods: Twenty 8-week-old female Sprague--Dawley rats were instilled with HCl in their bladders to create an IC/BPS model. The model rats were divided into three groups and orally administrated distilled water (control, n=4), concentrated SB (n=8), or pentosan polysulfate (PPS, n=8) daily. Pathologic inflammation grade (H&E staining), number of mast cells per square millimeter (toluidine blue staining), fibrotic changes (Masson's trichrome staining), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining) of bladder tissue samples were compared among the groups. Results: Compared to the control group, the SB and PPS groups showed reduced edema (5.25±0.96 vs. 2.25±0.46 vs. 2.50±0.54, p=0.004, p=0.005, respectively), number of mast cells (12.5±3.6 vs. 6.8±1.9 vs. 6.6±1.8, p=0.010, p=0.002, respectively), ratio of fibrotic submucosal tissue (63.9%±7.0% vs. 43.6%±9.9% vs. 40.5%±5.2%, p<0.001, p<0.001, respectively), and ratio of apoptotic nucleus (40.7%±11.7% vs. 7.7%±6.5% vs. 5.1%±4.9%, p<0.001, p<0.001, respectively). Conclusions: SB exhibited anti-inflammatory effects comparable to those of PPS in the HCl-induced chemical cystitis model. [ABSTRACT FROM AUTHOR]

To qualitatively assess the perception and experiences of bladder instillation for interstitial cystitis among women on Reddit, a widely used anonymous social media platform. "r/interstitialcystitis," a Subreddit with >27,000 subscribers, was queried for bladder instillation among women with interstitial cystitis in November 2023. Posts were analyzed qualitatively by 3 independent researchers. Grounded theory principles were applied to derive preliminary themes. These themes were then used to develop emergent themes. Sixty-three posts with 637 responses published between 2022-2023 were analyzed. Qualitative analysis yielded 4 themes: (1) IC/BPS anxiety and depression, (2) limited treatment options for IC/BPS pain, (3) exhausting all IC/BPS treatment options before bladder instillation, (4) bladder instillation ineffectiveness for IC/BPS pain. Three emergent concepts were derived: (1) a prevailing sense of desperation for relief among women with IC/BPS, (2) women are fearful and apprehensive about bladder instillation, (3) a perception of bladder instillation as the final recourse for women suffering from IC/BPS. This study represents the first evaluation of bladder instillation as a therapeutic from a social media community focused exclusively on IC/BPS. These results capture patient's experiences with nonurological associated syndromes and indicate a role for physicians to address mental health concerns in patients with IC/BPS, in addition to opportunities to improve patient education on bladder instillations. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: The objective was to explore the efficacy of micro-radiofrequency (micro-RF) therapy for treating non-Hunner interstitial cystitis (NHIC). Methods: Forty female NHIC patients were enrolled in this retrospective study from December 2021 to December 2023, with 20 receiving intravesical micro-RF therapy and 20 undergoing hydrodistension (HD). The primary evaluation index was the treatment success rate using the Global Response Assessment (GRA) scale. Secondary indexes included changes from baseline in the visual analog scale (VAS) for pain, Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale, and urination parameters. Outcomes were analyzed via t or nonparametric tests. Results: All 40 patients completed the treatment and follow-up; the treatment success rate of the micro-RF group (70%, 14 out of 20) was slightly higher than that of the HD group (50%, 10 out of 20) at 12 weeks post-treatment, with no significant difference (20%, p = 0.197). The VAS, ICSI, ICPI, PUF, day-time frequency, urgency episodes, and nocturia significantly decreased in both groups after treatment (p < 0.05). Further, the median decline ranges of VAS (−4.0 vs −3.0; p = 0.017; 95% CI −1.45, −0.15) and ICPI (−5.0 vs −4.0; p = 0.011; 95% CI −2.02, −0.283) were significantly larger in the micro-RF group. There were no significant differences in ICSI (−6.5 vs −6.0, p = 0.407), PUF (−10.0 vs. −8.0; p = 0.071), and urgency episodes (−5.5 vs −4.5; p = 0.570). Conclusions: Our study showed that the short-term overall efficacy of micro-RF therapy was better than hydrodistension, particularly in managing pain, and might be a new alternative treatment option for patients with NHIC. [ABSTRACT FROM AUTHOR]

Objective: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). Methods: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. Results: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow‐up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid‐fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. Conclusion: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis. Synopsis: Screening for confusable diseases, including bladder malignancy and tuberculosis, remains crucial for suspected interstitial cystitis patients, even if these conditions were not excluded initially. [ABSTRACT FROM AUTHOR]

Montelukast by inhibiting leukotriene receptors in the bladder can prevent the activation of mast cells. We investigated the effectiveness of Montelukast in reducing the symptoms of children with bladder pain syndrome (BPS). In this randomized clinical trial, children were allocated into groups of intervention (Montelukast and oxybutynin) and the control (oxybutynin). At the beginning and after 14 days, questions from mothers of children about their urinary condition were asked about the frequency of nocturnal enuresis, frequent urination, urinary incontinence, urinary urgency, and their pain severity. There was no significant difference between two groups in terms of frequency of nocturnal enuresis, frequent urination, urinary incontinence, and urinary urgency. Regarding the frequency of pain distribution, the frequency of pain-free people in the Montelukast group was higher than control group (84.4% vs 56.3%, P =.023). The results showed that adding Montelukast to oxybutynin has a significant decrease in pain in children with BPS. [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of nonpharmacological conservative therapies for women with CPP. A systematic search of electronic databases (Amed, CINAHL, PsycINFO, SportDiscuss, Medline, PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed in January 2023, and updated in December 2023. Randomized controlled trials comparing a nonpharmacological conservative therapy to inert (eg, placebo, usual care) or nonconservative (eg, surgical, pharmacological) treatment were included. Conservative therapies of interest to this review were: multimodal physical therapy, predominantly psychological approaches, acupuncture, and other tissue-based monotherapies (eg, electrophysical agents, manual stretching). All study data were aggregated, and analyses of the included studies were performed. Effects on pain; sexual measures; psychological and physical function; health-related quality of life; symptom severity/bother; pelvic floor muscle function and morphometry; perceived improvement; and adverse events were analyzed. Meta-analyses (random effects model) were conducted using postintervention scores for data that included similar interventions and outcomes. Standardized mean differences were calculated. A narrative summary of findings that could not be included in the meta-analysis is provided. The quality of the evidence was assessed with the Physiotherapy Evidence Database scale and the certainty of evidence with Grading of Recommendations, Assessment, Development, and Evaluations criteria. Of 5776 retrieved studies, 38 randomized controlled trials including 2168 women (mean age 35.1±8.6) were included. Meta-analyses revealed that multimodal physical therapy resulted in lower pain intensity compared to inert or nonconservative treatments in both the short (standardized mean difference −1.69, 95% confidence interval −2.54, −0.85; high certainty) and intermediate-terms (standardized mean difference −1.82, 95% confidence interval −3.13, −0.52; moderate certainty), while predominantly psychological approaches resulted in no difference in pain intensity (standardized mean difference −0.18, 95% confidence interval −0.56, 0.20; moderate certainty) and a slight difference in sexual function (standardized mean difference −0.28, 95% confidence interval −0.52, −0.04; moderate certainty). The level of evidence regarding the meta-analysis of the effects of acupuncture on pain intensity (standardized mean difference 1.08, 95% confidence interval −1.38, 3.54, nonstatistically significant results in favor of control treatment) precluded any statement of certainty. A limited number of trials investigated individual tissue-based monotherapies, providing a restricted body of evidence. This systematic review with meta-analysis revealed that multimodal physical therapy is effective in women with chronic pelvic pain with a high certainty of evidence. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a challenging chronic inflammatory condition affecting the urinary bladder, with limited treatment options. This study aims to assess the clinical efficacy of repeated intravesical platelet-rich plasma (PRP) injections for promoting urothelial regeneration and reducing inflammation in patients with IC/BPS and investigate its correlation with subjective and objective treatment-related outcomes. Materials and Methods: Four monthly intravesical PRP injections were given to 98 patients with non-Hunner-type IC/BPS. Treatment outcomes were assessed using a global response assessment (GRA) score 3 months posttreatment. In addition, clinical symptom scores, pain severity, voiding diary data, uroflowmetry parameters, and GRA scores were compared before and after treatment and between different treatment outcome groups (satisfactory: GRA≥2 unsatisfactory: GRA<2). Baseline urine biomarkers were analyzed to identify potential treatment outcome predictors. Results: After four PRP injections, 54 (55.1%) patients reported satisfactory outcomes. Lower urinary tract symptoms, bladder pain, urinary frequency, anxiety, and flow rate significantly improved from baseline (P < 0.05) in all patients, regardless of the treatment outcome. All patients experienced improved treatment outcomes and increased maximum bladder capacity with successive PRP treatments, and no major complications were reported. Urine biomarkers indicated elevated inflammation and oxidative stress biomarkers in patients with IC/BPS compared to controls. Conclusion: Repeated PRP injections are safe and effective for reducing symptoms and bladder pain and improving bladder capacity in a majority of IC/BPS patients, with better outcomes observed in patients with a mild form of bladder inflammation. These results support PRP as a promising novel bladder therapy for IC/BPS. [ABSTRACT FROM AUTHOR]

Purpose of Review: The management of noninfectious cystitis continues to evolve as new treatments continue to be developed and investigated. This review aims to synthesize the most recent data regarding management strategies for noninfectious cystitis focused on non-ulcerative, ulcerative, eosinophilic, and ketamine-induced cystitis. Recent Findings: Several novel treatments have shown promise as management options including combination antihistamine therapy, phosphodiesterase 5 inhibitors, alpha lipoic acid supplements, and onabotulinumtoxin A. Recent studies have also found pentosan polysulfate sodium to have adverse ophthalmologic effects. For patients with ulcerative cystitis, recent research has shown that fulguration with or without triamcinolone injections should not be delayed. Summary: The treatment of noninfectious cystitis should be patient specific based on factors including etiology and symptom profile. Multimodal regimens are often the most effective. Treatment should be started with conservative options and escalated as necessary to oral treatments, intravesical options, or procedural management. [ABSTRACT FROM AUTHOR]

Loris Cacciatore,1 Angelo Territo,2 Antonio Minore,1 Antonio Testa,1 Guglielmo Mantica,3 Francesco Esperto1 1Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico Di Roma, Rome, Italy; 2Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain; 3Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genoa, ItalyCorrespondence: Loris Cacciatore, Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy, Email loris.cacciatore@unicampus.itAbstract: Bladder pain Syndrome presents a multifaceted challenge in contemporary urological practice, marked by LUTS, negative behavioural, sexual, or emotional experiences, and the potential for sexual dysfunction. We meticulously explored the existing literature of conservative, non-invasive and invasive interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive BPS management. We delve into the effectiveness and safety profiles from behavioural approaches through lifestyle changes and physical therapy, to oral or intravesical medications, until the definitive surgical treatment. The best option evaluated is the involvement of a multidisciplinary team, including urologists, urotherapists, gynaecologists, pain specialists, primary care physicians and psychologists, educating those patients regarding the condition and its chronic course and tailoring the perfect treatment for each person. Despite this, BPS remains a challenge for urologists. Indeed, our objective is to contribute to the evolving landscape of BPS management, fostering informed decision-making and personalized care for individuals grappling with this challenging condition.Keywords: bladder pain syndrome, interstitial cystitis, lower urinary tract symptoms, females, continence, therapy, conservative treatment

Setting up the correct diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic inflammatory disease of the bladder, is a challenge, as there are neither diagnostic criteria nor reliable and non-invasive disease biomarkers available. The aim of the present study was to simultaneously determine matched serum- and urine-derived biomarkers of IC/BPS, which would provide additional insights into disease mechanisms and set the basis for further biomarker validation. Our study included 12 female patients with IC/BPS and 12 healthy controls. A total of 33 different biomarkers were measured, including cytokines and chemokines, proteins involved in extracellular matrix remodeling, adhesion molecules, growth factors, and markers of oxidative stress using enzyme linked immunoassays and multiplex technology. Heatmaps and principal component analysis based on significantly altered biomarkers, revealed urine- and serum-associated IC/BPS signatures that clearly differentiated IC/BPS patients from controls. Four biomarkers, including CCL11, BAFF, HGF and MMP9, were significantly upregulated in both serum and urine of patients with IC/BPS compared to controls. Serum levels of MMP9 were associated with disease severity and could distinguish well between IC/BPS patients with and without Hunner's lesions. Systemic levels of MMP9 can therefore mirror the local pathology within the bladders of IC/BPS patients, and MMP9 may prove to be a useful target for the development of novel therapeutic interventions. Utilizing a comprehensive panel of both urine and serum biomarkers, identified here, holds promise for disease detection in IC/BPS patients. [ABSTRACT FROM AUTHOR]

Introduction: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic and debilitating condition marked by bladder pain, urinary urgency, and frequency. The pathophysiology of IC/BPS remains poorly understood, with limited therapeutic options available. The role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its receptor PAC1 in IC/BPS has not been thoroughly investigated, despite their potential involvement in inflammation and sensory dysfunction. This study aims to examine the expression and functional role of the PACAP/PAC1 signaling pathway in the pathogenesis of IC/BPS. Methods: Bladder tissue samples from IC/BPS patients and a rat model of cystitis were analyzed to evaluate PACAP and PAC1 expression. Transcriptomic analysis, immunohistochemistry, and bladder function assays were employed to assess the correlation between PACAP/PAC1 activation, bladder inflammation, and sensory dysfunction. Additionally, modulation of the PACAP/PAC1 pathway was tested in rats to determine its effects on bladder inflammation and function. Results: Our results demonstrate significant upregulation of PACAP and PAC1 in both human bladder tissues from IC/BPS patients and in the rat cystitis model. This upregulation was associated with increased bladder inflammation and sensory dysfunction. Intervention with PACAP/PAC1 pathway modulation in rats resulted in a marked reduction in bladder inflammation and improvement in bladder function, suggesting the pathway's pivotal role in disease progression. Discussion: The findings provide compelling evidence that the PACAP/PAC1 pathway is involved in the inflammatory and sensory changes observed in IC/BPS. By targeting this signaling pathway, we may offer a novel therapeutic approach to mitigate the symptoms of IC/BPS. This study enhances our understanding of the molecular mechanisms driving IC/BPS and opens avenues for the development of targeted treatments. [ABSTRACT FROM AUTHOR]

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous, multifactorial disease with a high prevalence of somatic symptoms. A high percentage of women with IC/BPS also experience pelvic floor muscle pain (PFMP). This study investigated he association between PFMP and clinical characteristics in patients with IC/BPS. Method: This study evaluated the extent and severity of PFMP in women with IC and BPS. Demographics, sexual condition, IC symptom index (ICSI), IC problem index (ICPI), and Beck anxiety inventory and depression inventory were assessed. The objective assessment items included bladder wall thickness in computed tomography, urodynamic parameters, maximum bladder capacity (MBC) and glomerulation grade after cystoscopic hydrodistention, urine inflammatory proteins, and oxidative stress biomarkers. Result: A total of 9 women with IC and 83 with BPS were enrolled. A total of 85.8% of patients had PFMP. Patients with PFMP had higher rates of dyspareunia (p = 0.005), lack of sexual activity (p < 0.001), more comorbidities (p = 0.039), pain-predominant IC/BPS phenotypes (p = 0.04), higher IC symptoms (ICSI, p = 0.003; ICPI, p < 0.001), and higher levels of urinary biomarker MIP-1β (p = 0.004) than patients without PFMP. However, no significant correlation was found between PFMP and the bladder wall thickness, urodynamic parameters, MBC, or glomerulation grade. Conclusion: PFMP is present in a high percentage of patients with IC and BPS and associated with higher IC/BPS symptom score and dyspareunia, but not with MBC or glomerulation grade in patients with BPS. [ABSTRACT FROM AUTHOR]

Objective: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). Design: Cross‐sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. Setting: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). Population or Sample: A total of 100 participants. Methods: Descriptive and comparative analysis from flares questionnaire. Main Outcome Measures: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. Results: We received 100 responses of 104 questionnaires sent. Seventy‐six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non‐painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. Conclusions: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden. [ABSTRACT FROM AUTHOR]

Urostomy patients are rare as only about 5% of ostomates have urostomies. This can prove challenging because many healthcare professionals do not have experience caring for these patients and may be unfamiliar with their specific needs. As with other ostomates, urostomy patients require specialist nurses with the expertise to provide long-term support. Care for urostomy patients may be provided by urinary diversion specialists or stoma specialist nursing. Patient-centred pathways are needed to cater for their unique needs and ensure good patient outcomes and quality of life. People with urostomy have very post-operative need needs and inadequate care may result in hospital admissions. They need specialised long-term care. It is also crucial to educate the healthcare professionals responsible for their care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Special Issue "Machine Learning and Bioinformatics in Human Health and Disease" published in the International Journal of Molecular Sciences explores the transformative impact of computational methods on precision medicine. The collection of 11 articles showcases the integration of advanced ML techniques with biological sciences to advance disease prediction, biomarker discovery, and treatment optimization. The studies emphasize the importance of omics and multi-omics integration, unraveling disease mechanisms, advancements in disease risk prediction and early detection, explainability and transparency in ML models, and the challenges and future directions in ML-driven precision medicine. The research presented in this issue lays a strong foundation for the potential of ML and bioinformatics to enhance health outcomes and personalized care. [Extracted from the article]

Objective: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines. Materials and methods: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts. Results: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle–Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls. Conclusions: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The cat's urinary system is extremely sensitive. The term SUK (Feline Urological Syndrome, FLUTD) is used to describe a set of clinical symptoms associated with the lower urinary tract and urinary problems in general. There may be many causes, but recently the most common problem is idiopathic cystitis in cats, also known as stress cystitis or interstitial cystitis. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a likely underdiagnosed chronic pain syndrome consisting of pelvic pain lasting longer than 6 weeks plus lower urinary tract symptoms in the absence of infection or other identifiable cause. It is more common after 40 years of age. The etiology is unclear, but some patients have inflammatory findings in the bladder known as Hunner lesions. Due to its variable presentation, there is no standardized evaluation for diagnosis of IC/BPS. The history should include pain and urinary symptoms; associated comorbid disorders, including autoimmune and mental health conditions; and symptoms suggestive of other causes (eg, infection). Cystoscopy is not required but should be considered for patients with refractory symptoms and when Hunner lesions are suspected, such as in those older than 50 years or with comorbid autoimmune disorders and/or bladder-centric presentation (eg, predominance of urgency, frequency, low urine volumes). Treatment is often multimodal, including behavior modifications, stress management, and nonpharmacologic therapy (eg, pelvic floor physical therapy). Oral pharmacotherapy can be considered, but no guidelines exist on preferred agents. Referral for procedural treatments can also be considered for refractory cases. Patients should understand that no treatments are definitively successful, and recurrences and flare-ups often occur. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review examines laser therapy for bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia, focusing on efficacy, mechanisms, and common pathophysiological pathways. Recent Findings: Studies show promising results for non-ablative Er:YAG and Nd:YAG lasers in treating vulvodynia and associated conditions in BPS/IC patients. Ho:YAG laser demonstrates potential for Hunner's lesions. Histological improvements and symptom relief have been reported. Research highlights shared pathophysiological mechanisms between BPS/IC and vulvodynia, including mast cell involvement, neurogenic inflammation, and central sensitization. Furthermore, machine learning-based clustering analysis has identified novel subtypes of BPS/IC. Summary: Laser therapy shows potential in managing BPS/IC and vulvodynia, with evidence suggesting common underlying mechanisms. Larger, long-term studies are needed to establish efficacy, safety, and optimal protocols, as well as to further elucidate shared pathophysiological pathways. The author proposes developing personalized medicine approaches using regular clustering analysis and artificial intelligence, which may lead to adaptive treatment strategies based on patients' changing symptom profiles. [ABSTRACT FROM AUTHOR]

Purpose of Review: Dimethyl Sulfoxide (DMSO) remains an option for the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) in select patients. This review will discuss the mechanism of action and the role of intravesical DMSO cocktail therapy, as well as outcomes and adverse events for this therapy. Recent Findings: Several, but not all historical studies have demonstrated some efficacy for DMSO in the treatment of BPS/IC symptoms including pain and lower urinary tract symptoms such as urgency and frequency. Although DMSO appears superior to placebo, there remain few well-done studies demonstrating support for DMSO use versus other intravesical or alternative BPS/IC treatments. AUA guidelines regarding the role of DMSO have been recently updated. Summary: Despite a long history of utilization in the treatment of BPS/IC, the literature supporting its use is not particularly robust. Current AUA guidelines support DMSO as an option in selected patients with a modest level of evidence. [ABSTRACT FROM AUTHOR]

Hunner‐type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next‐generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC‐affected bladder tissue. Subsequent analysis of the B‐cell receptor repertoire revealed spatial and temporal expansion of B‐cell clones. The extent of B‐cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B‐cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Epidemiological studies have demonstrated the clinical link between Hunner interstitial cystitis (HIC) and autoimmune diseases (ADs), suggesting potential shared genetic bases for their comorbidity. We aimed to investigate the shared genetic architecture and causal relationships between HIC and ADs. Methods: We conducted a genome-wide cross-trait study with ~170000 individuals of East Asian ancestry to investigate the shared architecture between HIC and ADs. Bidirectional Mendelian randomization (MR) was used to assess potential causal relationships and a multi-trait analysis of GWAS (MTAG) was conducted to identify their associated pleiotropic loci. Fine-mapping analysis narrowed candidate gene susceptibility loci and colocalization analysis was performed to identify shared variants at specific locus. Lastly, transcriptome-wide association (TWAS) and functional analysis were utilized to explore potential shared gene-tissue associations. Results: Through bidirectional MR analysis, we observed a positive causal effect of AIH(ORIVW=1.09, PIVW=1.00×10-3) and RA (ORIVW=1.47, PIVW<1.00×10-4) on HIC and a negative causal effect of UC on HIC (ORIVW=0.89, PIVW< 1.00×10-4). Furthermore, we unveiled a robust positive causal effect of HIC on T1D(ORConMix=1.05, PConMix=1.77×10-3). Cross-trait meta-analysis identified a total of 64 independent SNPs associated with HIC and ADs. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to the autoimmune system. Conclusions: Our findings might offer insights into the shared underlying etiology of HIC and ADs. [ABSTRACT FROM AUTHOR]