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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., Competing Interests: Declarations. Conflict of interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: We developed an algorithm-based mobile texting platform for promoting self-management in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Our aim was to measure the feasibility, usability, and potential utility of the platform., Methods: A texting platform that delivered 4 treatment modules (education and behavioral modification, cognitive behavioral therapy, pelvic floor physical therapy, and guided mindfulness practices) and an automated weekly message over 6 weeks was developed. Feasibility and usability were determined using patient engagement (proportion of platform messages to which patients responded) and System Usability Scale. Satisfaction with patient-physician communication questionnaire, Pain Self-Efficacy Scale, and Interstitial Cystitis Symptom and Problem Index were administered before and after the intervention., Results: Engagement with the platform in 52 female patients with IC/BPS (median age [IQR] 40 [30-48] years) was 76.9%. The commonest module selected by patients was pelvic floor physical therapy (50%) followed by cognitive behavioral therapy (34%) and guided mindfulness (15%). System usability score (median, IQR) was 87 (83-95), indicating high usability. Satisfaction with patient-physician communication improved significantly (median change, 4; IQR, 1-9; P < .001). Pain self-efficacy score improved from moderate impairment at baseline to minimal impairment at 6 weeks (median change, 10; IQR, 2-18; P < .001). Urinary symptoms scores also improved (median change Interstitial Cystitis Symptom Index, -3; IQR, -5 to -1.5; P < .001, Problem Index, -2; IQR, 5.5 to -0.5; P < .001)., Conclusions: An automated mobile platform has the potential for improving access to self-management strategies and easing clinicians' challenge of counseling patients with IC/BPS during time-limited in-person visits., Trial Registration: ClinicalTrials.gov Identifier: NCT05260112.

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., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective cross-sectional study was approved by the Regional Ethics Committee of Kanagawa Dental University in 2023 (approval number 959 as The UNICORN-4 Study). The study was conducted in accordance with the Declaration of Helsinki and all relevant guidelines and regulations. All the participants provided written informed consent. Consent for publication: Consent for publication was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To assess differences in clinical presentation and illness impact in men and women presenting with urologic chronic pelvic pain syndrome (UCPPS) and between men diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Methods: 356 men and 605 women from six sites across the United States were assessed using a comprehensive set of demographic, symptom, and illness impact measures. Multivariable regression analyses examined differences between men and women and between men previously diagnosed with CP/CPPS or IC/BPS. In a stepwise manner, analyses tested group differences, controlling for demographic variables including symptom duration and presence of bladder pain that varied with filling and voiding., Results: Men diagnosed with IC/BPS had the most severe UCPPS symptoms, followed by women with IC/BPS, and then men with CP/CPPS only. While men and women showed similar patterns of symptoms across most of the variables, women had increased widespread non-pelvic pain, greater pelvic floor tenderness on exam, and higher self-reported sensory sensitivity compared to men. About 60% of men diagnosed with CP/CPPS only reported bladder symptoms of painful filling or relief with voiding., Conclusions: A generally shared symptom pattern was found across men and women irrespective of diagnostic labels suggesting the use of key marker symptoms, such as severity of bladder symptoms and widespread pain, to better identify subgroups of UCPPS rather than diagnostic category. Women may have an increased likelihood of increased sensitivity and central sensitization than men, including those men with IC/BPS., Trial Registration: ClinicalTrials.gov Identifier: NCT02514265 - MAPP Research Network: Trans-MAPP Study of Urologic Chronic Pelvic Pain: Symptom Patterns Study (SPS)., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic syndrome involving urinary frequency, urgency, and bladder discomfort. These IC/BPS symptoms can significantly impact individuals' quality of life, affecting their mental, physical, sexual, and financial well-being. Individuals sometimes rely on peer-to-peer support to understand the disease and find methods of alleviating symptoms. The only US Food and Drug Administration-approved medication to treat IC/BPS is pentosan polysulfate sodium (PPS). However, ocular pigmentary maculopathy has been described in some individuals, with greater severity associated with prolonged PPS exposure., Objective: While prior research has separately assessed the benefits and side effects of PPS, this study sought to identify (1) sentiments of individuals with IC/BPS toward PPS and (2) topics discussed by individuals with IC/BPS in conjunction with PPS through use of an internet peer-to-peer forum., Methods: Data were collected from Inspire-an anonymous web-based health community where individuals gather by condition to find support and information. Sentiment analysis and percentages of negative, positive, and neutral sentiment for PPS discussions encompassing each topic was conducted using VADER (Valence Aware Dictionary for Sentiment Reasoning). Topic modeling was conducted using latent Dirichlet allocation. Words with the highest probability were ranked to categorize each topic, and authors manually investigated and labeled discussions., Results: There were 354 forum posts related to PPS. Topic modeling with latent Dirichlet allocation revealed 5 topic categories: "ineffectiveness or discontinued use," "alternative treatments," "personal treatment suggestions based on experience," "severe side effects," and "risk of long-term use." Topics related to "severe side effects" and "risk of long-term use" garnered less discussion, with the former also having the lowest positive sentiment (4.28, 14.29%). The topic "ineffectiveness or discontinued use" was most frequently discussed. This topic also had the highest percentage of negative posts (52/152, 34.21%). However, the average compound score was within the neutral compound score range (-0.094, SD 0.625). In addition, forum data highlighted individuals' acknowledgment of the efficacy of PPS in improving their quality of life, with statements such as "saved my sanity" being representative. The overall compound individuals' sentiment toward PPS was -0.083, split across 32.49% (115/354) negative, 22.03% (78/354) positive, and 45.48% (161/354) neutral sentiment categories., Conclusions: The overall authentic sentiment toward PPS is broad but balances to neutral. This neutral sentiment suggests that while some individuals express concerns about the side effects and long-term risks associated with PPS, others appreciate its positive impact on their quality of life. This research confirms that individuals with IC/BPS actively engage with health forums like Inspire to seek information, share their experiences, and explore different treatment options. As IC/BPS remains a complex syndrome, this study highlights the value of patient-led discussions in informing treatment decisions. Furthermore, these findings suggest that health care providers might benefit from considering the insights shared on peer-to-peer forums to better understand individual preferences, concerns, and expectations., (© Yulin Hswen, Qiuyuan Qin, Pressley Smith, Alison Swierczynski, Stuart Bauer, Erika Ladson, Amanda Leigh Garrett, Catherine A Brownstein. Originally published in JMIR Formative Research (https://formative.jmir.org).)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe clinical manifestations of patients with interstitial cystitis and bladder pain syndrome (IC/BPS) using a patient registry in Japan., Methods: This retrospective cohort study utilized a patient registry supported by the Japanese Ministry of Health, Labor, and Welfare. Patients were classified as IC or BPS based on cystoscopic findings. Data on demographics, comorbidities, symptom severity, pain intensity, and bladder function were collected and we evaluated the differences in clinical characteristics between IC and BPS, and used multivariate analysis to search for additional factors that might contribute to pain., Result: A data set comprising 529 patients was obtained from 14 university hospitals. 66.5% of the cases were classified as IC and 33.5% as BPS. IC patients were significantly aged and female-dominant. Comorbidities such as autoimmune diseases were more prevalent in IC patients. All of the symptom severity, quality of life impairment, and bladder function were significantly worse in patients with IC. Urinary frequency and maximum voided volume on the Frequency-volume chart were 18.8 times and 15.0 times, and 160.9 and 214.1 mL, respectively. Bladder capacity under anesthesia was 293.8 and 472.6 mL, respectively. Maximum voided volume and the number of Hunner lesions were significant predictors of pain in IC patients., Conclusion: The analysis revealed clinical manifestations of IC/BPS using the largest cohort in Japan. The results indicated higher age, higher female proportion, and higher symptomatic and functional severity in IC patients compared to BPS., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

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., Competing Interests: Shinhoon Kang is an employee of Vitamin Tree Labs Corp. The other authors have nothing to disclose., (© The Korean Urological Association.)

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., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

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., Competing Interests: Declarations. Ethical approval: This study was performed in Hualien Tzu Chi Hospital and was approved by the ethics committee of the hospital (IRB: 113-151-B, dated August 10, 2024-August 10, 2025). Informed consent: Informed consent was obtained from all individual participants included in the study. All parts of this study comply with the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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., (© 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.)

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., Competing Interests: The authors declare no conflict of interest.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by pelvic pain and urinary urgency and frequency with an unclear etiology. Emerging evidence implicates microbiome dysbiosis-disruptions in the microbial communities inhabiting the body-in IC/BPS pathophysiology. This review synthesizes the literature on microbial alterations in IC/BPS, including urinary, vaginal, and gastrointestinal microbiota, and their interactions with host inflammatory and metabolic pathways. PATIENT SUMMARY: We reviewed studies from the past 10 years on microbial communities in the body for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Studies have revealed significant changes in microbial species for these patients, especially in urine. However, research on whether IC/BPS can be treated with interventions to modify microbial communities in the body is still needed., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ke, Zhu, Zhang, Wang, Ding, Su, Wang and Xu.)

Background: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than 6 weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed., Objective: To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of IC/BPS., Study Design: Patients with O'Leary-Sant (OLS) questionnaire scores of ≥6, meeting clinical criteria for IC/BPS, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months posttreatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates., Results: Forty-seven patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months posttreatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index [ICSI] -6.3 (confidence interval [CI] -8.54, -3.95), P<.0001; Interstitial Cystitis Problem Index [ICPI] -5.9 (CI -8.18, -3.57), P<.0001). At 2 months posttreatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3±4.5 [onabotulinumtoxinA] vs 9.6±4.2 [instillation], P=.008; ICPI 5.9±5.1 [onabotulinumtoxinA] vs 8.3±4.0 [instillation], P=.048). The difference in OLS scores between groups did not persist at 6 to 9 months posttreatment. There were no statistically significant differences between baseline and posttreatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6 to 9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment., Conclusion: Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with IC/BPS, with significant clinical improvement demonstrated at 2 months posttreatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment., (Published by Elsevier Inc.)

Aims: Compensatory coping, or maladaptive alterations in behavior with the intention of preventing or managing symptoms, is increasingly being explored as a key factor in how people respond to bladder conditions. Preliminary investigations have identified relations between coping behaviors and psychological distress in urologic conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS). However, previous explorations of coping have not accounted for heterogeneity in coping behaviors or addressed the likelihood that some coping behaviors may be more adaptive than others. This study sought to examine how two specific types of coping behaviors, primary control coping and disengaged coping, are related to distress and symptoms in IC/BPS, and to explore the potential role of pain phenotype in this relationship., Materials and Methods: A secondary data analysis was conducted with a large community data set (N = 677 women with IC/BPS) and employed descriptive and inferential statistics to characterize coping patterns and explore novel predictors of distress., Results: Results indicated that almost all participants engaged in at least one compensatory coping behavior within the last week. Both types of coping behaviors correlated with psychological symptoms, and when controlling for relevant clinical variables (i.e., age and severity of urinary symptoms), disengaged coping behaviors were significantly associated with psychological distress. Further, the addition of pain phenotype to multiple regression models resulted in a more effective predictive model when considering the relation between coping behaviors and depression., Conclusions: By investigating more deeply the relationship between coping and distress, understanding of potential risk factors and mechanisms is increased, offering valuable insights for intervention strategies for IC/BPS patients., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objective: To evaluate the efficacy of cyclophosphamide (CYP) at different doses in replicating the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) in an animal model, thereby providing an experimental basis for understanding the pathophysiology of IC/BPS and assessing treatment strategies., Methods: Twenty-eight female Sprague-Dawley rats aged seven weeks were divided into four groups: Group a (25 mg/kg CYP), group b (75 mg/kg CYP), group c (125 mg/kg CYP), and group d (a control group). The rats were injected intraperitoneally with either CYP or saline solution. Evaluations included urine spot tests, von Frey filament pain threshold tests, urodynamic examinations, and histological assessments., Results: The study found that the 25 mg/kg CYP dosage significantly outperformed higher doses in simulating bladder dysfunction and inflammatory responses while minimizing the impact on the rats' physiological functions. Specifically, urine spot area, group a showed a significant reduction in urine spot area compared with the control group ( P < 0.05), while groups b and c did not show significant differences. Pain threshold: The von Frey filament test indicated increased visceral pain in group a, aligning closely with IC/BPS patient symptoms, without a significant increase in urination frequency. Urodynamic assessments: Group a exhibited decreased bladder compliance and reduced maximum bladder capacity ( P < 0.05), with no significant differences in baseline bladder pressure and maximum detrusor pressure across all groups. Histological analysis: Hematoxylin-eosin (HE) staining revealed that bladder tissue in group a had moderate inflammatory reactions, whereas groups b and c showed severe inflammation and tissue damage, correlating with the higher doses of CYP. Furthermore, the urine spot tests and von frey filament tests provided quantitative data supporting the model's reliability, urine spot count, group a had an average urine spot count of (15±3) spots, significantly higher than the control group's (5±2) spots ( P < 0.01). Nociceptive score: Group a nociceptive score increased to 0.5±0.1, indicating heightened pain sensitivity compared with the control group 0.10±0.05 ( P < 0.01)., Conclusion: The 25 mg/kg CYP demonstrated significant advantages in simulating the key features of non-ulcerative IC/BPS, summarizing the main aspects of the human condition, including persistent visceral pain and mild inflammatory reactions in bladder tissue. These findings offer substantial experimental support for drug development and treatment research in IC/BPS and provide new insights into the complex patho-physiology of the disease.

Background: Vulvodynia (VVD) is a debilitating chronic vulvar pain significantly affecting patients' quality of life. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and complex illness characterized by an unpleasant sensation related to the filling of the bladder and it strongly impacts patients' lives. The exact mechanisms of the two syndromes remain unknown, but there is an overlap between suspected pathophysiologies., Objective: To present an overview of the current research on the association between VVD and IC/BPS., Search Strategy: A systematic search of three electronic databases was conducted. Studies examining the correlation between VVD and IC/BPS with male and female patients aged over 18 years were included., Selection Criteria: Studies assessing the coexistence of VVD and IC/BPS were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded., Data Collection and Analysis: Two reviewers screened the studies for eligibility. Eligible studies were screened for quality., Main Results: A total of 13 studies were included in the final review. Among them, 11 presented a positive association between the two syndromes. The studies highlighted that VVD and IC/BPS share common comorbidities and possibly etiopathogenic pathways., Conclusion: VVD and IC/BPS are both complex and multifactorial syndromes. This review highlights an association between them, but additional studies on the topic should be conducted for a more precise conclusion., (© 2024 International Federation of Gynecology and Obstetrics.)

Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) and migraine are both chronic pain syndromes with similarities in pathophysiology and clinical presentation. This study aims to investigate the clinical characteristics of IC/BPS patients with comorbid migraine., Methods: A retrospective analysis was conducted on the clinical data of 303 IC/BPS patients treated at the Second and Third Affiliated Hospitals of Qiqihar Medical University from January 2019 to December 2023. Disease severity, bladder pain and/or headache intensity, anxiety, depression, sleep quality, somatic symptoms, and quality of life were assessed using the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), Numerical Rating Scale (NRS), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), Self-Rating Somatic Symptom Scale (SSS), and Visual Analogue Scales (VAS) for quality of life. Serum inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6)] and pain mediators [prostaglandin E2 (PGE2), substance P (SP)] were measured using enzyme-linked immunosorbent assay (ELISA)., Results: Among the 303 IC/BPS patients, 87 (28.71%) had comorbid migraine. Compared to IC/BPS patients without migraine, those with migraine had a longer IC/BPS duration, higher ICSI scores, elevated bladder pain NRS, GAD-7, PHQ-9, PSQI, SSS, VAS scores for quality of life, and higher serum levels of IL-1β, IL-6, PGE2, and SP, along with fewer weekly exercise sessions (all P <0.05). Among the 87 IC/BPS patients with migraine, the 39 patients with severe IC/BPS had higher headache frequency, longer headache duration, and significantly higher headache NRS, bladder pain NRS, GAD-7, PSQI, SSS, VAS scores for quality of life, and serum levels of IL-1β, IL-6, PGE2, and SP compared to the 48 patients with mild-to-moderate IC/BPS (all P <0.05). In IC/BPS patients with migraine, ICSI scores were positively correlated with headache NRS ( r =2.072, P =0.032), headache frequency ( r =2.184, P =0.028), headache duration ( r =1.843, P =0.041), bladder pain NRS ( r =2.295, P =0.023), GAD-7 scores ( r =2.210, P =0.025), SSS scores ( r =3.159, P =0.009), and VAS scores for quality of life ( r =2.891, P =0.013) but not with PSQI scores ( r =1.515, P =0.070)., Conclusions: Patients with IC/BPS and comorbid migraine exhibit more severe clinical and psychological symptoms. The severity of IC/BPS symptoms is associated with migraine severity.

Background: Several observational studies have indicated an association between interstitial cystitis and the composition of the gut microbiota; however, the causality and underlying mechanisms remain unclear. Understanding the link between gut microbiota and interstitial cystitis could inform strategies for prevention and treatment., Methods: A two-sample Mendelian randomization analysis was conducted using published genome-wide association study summary statistics. We employed inverse variance weighted, weighted mode, MR-Egger, weighted median, simple mode, and cML-MA methods to investigate the causal relationship between gut microbiota and interstitial cystitis. Sensitivity analysis was performed to validate the results. Relevant gut microbiota was examined through reverse MR. Single nucleotide polymorphisms were annotated using FUMA to identify genes associated with these genetic variants, thereby revealing potential host gene-microbiota associations in interstitial cystitis patients., Results: Eight bacterial taxa were identified in our analysis as associated with interstitial cystitis. Among these, Butyricimonas , Coprococcus , Lactobacillales , Lentisphaerae , and Bilophila wadsworthia were positively correlated with interstitial cystitis risk, while taxa such as Desulfovibrio piger , Oscillibacter unclassified and Ruminococcus lactaris exhibited protective effects against interstitial cystitis. The robustness of these associations was confirmed through sensitivity analyses. Reverse MR analysis did not reveal evidence of reverse causality. Single nucleotide polymorphisms were annotated using FUMA and subjected to biological analysis. Seven hub genes (SPTBN1, PSME4, CHAC2, ERLEC1, ASB3, STAT5A, and STAT3) were identified as differentially expressed between interstitial cystitis patients and healthy individuals, representing potential therapeutic targets., Conclusion: Our two-sample Mendelian randomization study established a causal relationship between gut microbiota and interstitial cystitis. Furthermore, our identification of a host gene-microbiota association offers a new avenue for investigating the potential pathogenesis of interstitial cystitis and suggests avenues for the development of personalized treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fu, Zhao, Zhou, Lv, Jin, Zhou, Liu and Feng.)

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes., Ethics and Dissemination: All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20-01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences., Trial Registration: ClinicalTrials.gov NCT04734847. Registered on February 1, 2021., (© 2024. The Author(s).)

Introduction and Hypothesis: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS., Methods: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium., Results: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies., Conclusion: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation., (© 2024. The International Urogynecological Association.)

The clinical guidelines for interstitial cystitis (IC) and bladder pain syndrome (BPS) have been revised by updating our previous guidelines. The symptoms of IC and BPS, collectively called as hypersensitive bladder (HSB) symptoms, are virtually indistinguishable between IC and BPS; however, IC and BPS should be considered as a separate entity of disorders. We define IC as a bladder disease with Hunner lesions, usually associated with HSB symptoms and bladder inflammation, and BPS as a condition with HSB symptoms in the absence of Hunner lesions and any confusable diseases. Pathophysiology totally differs between IC and BPS. IC involves immunological inflammation probably resulting from autoimmunity, while BPS is associated with the interaction of multiple factors such as neurogenic inflammation, exogenous substances, urothelial defects, psychological stress, and neural hyperactivity. Histopathology also differs between IC and BPS. IC is associated with severe inflammation of the whole bladder accompanied by plasma cell infiltration and urothelial denudation, while BPS shows little pathological changes. Management should begin with a differential diagnosis of IC or BPS, which would require cystoscopy to determine the presence or absence of Hunner lesions. The patients should be treated differently based on the diagnosis following the algorithm, although pain management would be common to IC and BPS. Clinical studies are also to be designed and analyzed separately for IC and BPS., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Major depressive disorder (MDD) and interstitial cystitis (IC) are two highly debilitating conditions that often coexist with reciprocal effect, significantly exacerbating patients' suffering. However, the molecular underpinnings linking these disorders remain poorly understood., Methods: Transcriptomic data from GEO datasets including those of MDD and IC patients was systematically analyzed to develop and validate our model. Following removal of batch effect, differentially expressed genes (DEGs) between respective disease and control groups were identified. Shared DEGs of the conditions then underwent functional enrichment analyses. Additionally, immune infiltration analysis was quantified through ssGSEA. A diagnostic model for MDD was constructed by exploring 113 combinations of 12 machine learning algorithms with 10-fold cross-validation on the training sets following by external validation on test sets. Finally, the "Enrichr" platform was utilized to identify potential drugs for MDD., Results: Totally, 21 key genes closely associated with both MDD and IC were identified, predominantly involved in immune processes based on enrichment analyses. Immune infiltration analysis revealed distinct profiles of immune cell infiltration in MDD and IC compared to healthy controls. From these genes, a robust 11-gene (ABCD2, ATP8B4, TNNT1, AKR1C3, SLC26A8, S100A12, PTX3, FAM3B, ITGA2B, OLFM4, BCL7A) diagnostic signature was constructed, which exhibited superior performance over existing MDD diagnostic models both in training and testing cohorts. Additionally, epigallocatechin gallate and 10 other drugs emerged as potential targets for MDD., Conclusion: Our work developed a diagnostic model for MDD employing a combination of bioinformatic techniques and machine learning methods, focusing on shared genes between MDD and IC., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research., (© 2024. The Author(s).)

Introduction: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients., Methods: During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank., Results: Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled., Conclusions: The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Although the cause of interstitial cystitis/painful bladder syndrome (IC/PBS) remains unknown, autoimmune involvement has been strongly suggested to be a contributing factor. To elucidate the pathophysiology of IC/PBS, we characterized the experimental autoimmune cystitis (EAC) in rats. Adult female Sprague-Dawley rats were divided into the EAC and control groups. The EAC rats were generated by administrating a homogenate of donor rat bladder tissue as a bladder antigen. The characteristics of the two groups were determined by evaluating pain behavior and conducting cystometry, histopathology, and molecular analyses. The EAC rats showed: 1 ) a decreased paw withdrawal threshold, 2 ) a reduced intercontraction interval on cystometry, 3 ) the irregular surfaces of the umbrella cells of epithelium throughout the bladder wall, 4 ) accumulation of stress granules in the bladder and vascular endothelium, 5 )the increased expression of genes related to inflammation and ischemia at the mRNA and protein levels, 6 ) a significantly increased paw withdrawal threshold with pain treatment, and 7 ) the induction of glomerulation of the bladder wall, epithelium denudation, and lymphocyte infiltration in the interstitium by bladder distension. These results suggest that the EAC rats showed pain and frequent urination with the overexpression of inflammatory chemokines, reflecting clinical IC/BPS, and the bladder epithelium and vascular endothelium may be the primary sites of IC/BPS, and bladder injury, such as bladder distension, can cause progression from BPS to IC with Hunner lesions. NEW & NOTEWORTHY The experimental autoimmune cystitis model rats showed pain and frequent urination with the overexpression of inflammatory chemokines, reflecting clinical interstitial cystitis/painful bladder syndrome (IC/PBS), and the bladder epithelium and vascular endothelium may be the primary sites of IC/BPS, and bladder injury, such as bladder distension, can cause progression from BPS to IC with Hunner lesions.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS., (© 2024. The Author(s).)

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease with limited treatment options. Current multidisciplinary approach targeting bladder inflammation and urothelial dysfunction has limited durable effect that major surgery is ultimately required for both Hunner and non-Hunner type IC. Various investigational attempts are underway to avoid such operations and preserve the urinary bladder. Stem cell therapy is a fascinating option for treating chronic illnesses. Stem cells can self-renew, restore damaged tissue, and have paracrine effects. The therapeutic efficacy and safety of stem cell therapy have been demonstrated in numerous preclinical models, primarily chemically induced cystitis rat models. Only one clinical trial (phase 1 study) has investigated the safety of human embryonic stem cell-derived mesenchymal stem cells in three Hunner-type IC patients. Under general anesthesia, participants underwent cystoscopic submucosal stem cell injection (2.0 × 10 7 stem cells/5 mL). No safety issues were reported up to 12 months of follow-up and long-term follow-up (up to 3 years). Although there were variations in therapeutic response, all patients reported significant improvement in pain at 1 month postoperatively. One patient underwent fulguration of the Hunner lesion after the trial, but others reported an overall improvement in pain. The analysis on phase 1/2a trial which had several modifications in protocol is currently ongoing. Despite several limitations that need to be overcome, stem cell therapy could be a potential therapeutic option for treating IC/BPS. Clinical outcome on phase 1/2a trial is important and might provide more insight into the clinical application of stem cell therapy for IC/BPS., (© 2024 John Wiley & Sons Australia, Ltd.)

Aim: Validation of the recently published newer clinical scoring system for bladder pain syndrome/interstitial cystitis and comparison of the results with the pre-existing standard O'Leary-Sant score., Introduction: The symptoms are our primary guide to disease severity analysis, treatment, and response monitoring. The combined ICSI/ICPI (O'Leary-Sant Interstitial Cystitis Symptom and Problem Index) consist of a four-item symptom and problem index focusing on urgency, frequency, nocturia, and pain. A new scale, assigning more weight to pain and nocturia and adding the domains of sexual dysfunction and psychological impact, has been published by one of the authors (El Khoudary et al. J Women's Health 2002. 18:1361-1368; 7)., Material and Methods: This is a prospective study conducted to validate a newer clinical scoring system, namedht e 'Apollo Clinical Scoring' (ACS) system for patients with bladder pain syndrome/ interstitial cystitis (BPS/IC), and to compare its outcome with the simultaneously applied standard O'Leary-Sant (OLS) score. Thirty-five patients of BPS/IC diagnosed using the ESSIC definition were enrolled in the study and followed for 6 months. Intraclass correlation coefficient (ICC) for test-retest reliability, and Cronbach's α for measure of internal consistency, were applied to both scoring systems., Results: Intraclass correlation coefficient for ACS was 0.715 and for OLS was 0.689. Cronbach's α for ACS was 0.736 and for OLS was 0.698., Conclusion: The present study suggests that the recently devised Apollo Clinical Scoring (ACS) system for patients of BPS/IC is internally consistent and a reliable scoring system. When compared with OLS in parallel setting, the newer ACS appeared to be marginally better., (© 2024. The International Urogynecological Association.)

Introduction and Hypothesis: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome., Methods: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval., Results: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7)., Conclusions: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients., (© 2024. Crown.)

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by chronic pelvic pain and usually accompanies lower urinary tract symptoms. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory IC/BPS patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months., Materials and Methods: Consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized amniotic membrane. Clinical evaluation and patient-reported outcome measurements including Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB) were assessed., Results: Twenty-five consecutive recalcitrant IC/BPS patients were included in the study with an average age of 47.4 ± 14.4 years (29-67 years). After ABT, the IC/BPS symptoms improved gradually up to 3 months in all patients with an average improvement in ICSI, ICPI, BPIC-SS and OAB score of 72.8%, 71.9%, and 66.6%, (p < 0.001) respectively, at 3 months. At 4 months after ABT, 7 patients experienced a rebound in symptoms and requested another injection which resulted in a significant improvement in IC/BPS symptoms after 2, 4, and 8 weeks (p < 0.01). For the 18 patients who received only one injection, the IC/BPS symptoms were still significantly lower at 5 and 6 months compared to baseline (p < 0.01), suggesting a possible durable effect based on the ICSI, ICPI, BPIC-SS, and OAB questionnaire scores., Conclusions: ABT provided an improvement in pain and lower urinary tract symptoms up to 6 months post-treatment in some refractory IC/BPS patients.

Introduction: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation., Methods: Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety., Results: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23-74 years; mean number of UTI episodes in previous year 6.1 +/- 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine., Conclusion: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system.

Purpose: The relationship between obstructive sleep apnea (OSA) and bladder pain syndrome/interstitial cystitis (BPS/IC) remains uncertain. Therefore, this study aimed to compare the frequency of BPS/IC seen in women diagnosed with OSA and in women without OSA., Material and Methods: The study included a patient group of women with OSA and a control group of women without OSA. All the study participants were administered the Berlin Questionnaire, Epworth Sleepiness Scale, Interstitial Cystitis Symptom Index (ICSI), and the Interstitial Cystitis Problem Index (ICPI). Differences between the women with OSA and the control group were examined., Results: The study sample consisted of 46 women with OSA and 46 controls. No significant difference was determined between the OSA and control groups concerning age and body mass index (p = 0.810, p = 0.060, respectively). The ESS was greater in the OSA group than in the control group (p = 0.007). The median (IQR) ICSI was 8 (4-11.25) in women with OSA and 5 (1.75-7.15) in controls (p < 0.001). The median (IQR) ICPI was 7 (6.00-10.25) in women with OSA and 6 (1.75-8.00) in controls (p < 0.001).  CONCLUSIONS: The ICSI symptoms and subsequent problems in daily life caused by the symptoms (ICPI) were experienced at a higher rate in patients with OSA than in the control group. There is an association between BPS/IC and OSA., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease., Methods: Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, T -test and logistic regression analysis., Results: Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant ( p < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS., Conclusions: Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence., Aim: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms., Methods: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests., Outcomes: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis., Results: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women., Clinical Implications: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner., Strengths and Limitations: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation., Conclusion: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this study, it was aimed to investigate the effects of berberine (BER) and curcumin (CUR) in the experimental model of cystitis induced by cyclophosphamide (CYP). A total of 36 Wistar-Albino female rats were used in the study. Rats were randomly divided into six groups (n = 6). Normal control group, dimethyl sulfoxide (DMSO) group, CYP group (75 mg/kg), CYP + BER (75 mg/kg CYP and 50 mg/kg BER), CYP + CUR group (75 mg/kg CYP and 50 mg/kg CUR), CYP + BER + CUR group (75 mg/kg CYP and 50 mg/kg BER and 50 mg/kg CUR). Severe edema, hyperemia, hemorrhage, necrosis, and thinning of the epithelial layer were observed in the CYP group. BER and CUR treatment significantly reduced these pathologies. Masson-Trichrome staining was severe in the CYP group and moderate in the CYP + BER, CYP + CUR, and CYP + BER + CUR groups. In the CYP group, there was a severe expression of caspase-3, TNF-α and IL-6, and mild expression of IL-10. BER and CUR treatment decreased the expression of caspase-3, TNF-α, and IL-6 and increased the expression of IL-10. The findings of the study reveal that BER and CUR treatments may reduce CYP-induced bladder damage by reducing apoptosis and inflammation and ameliorating histopathological changes., (© 2023 Wiley Periodicals LLC.)

Introduction and Hypothesis: As interstitial cystitis/bladder pain syndrome (IC/BPS) likely represents multiple pathophysiologies, we sought to validate three clinical phenotypes of IC/BPS patients in a large, multi-center cohort using unsupervised machine learning (ML) analysis., Methods: Using the female Genitourinary Pain Index and O'Leary-Sant Indices, k-means unsupervised clustering was utilized to define symptomatic phenotypes in 130 premenopausal IC/BPS participants recruited through the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network. Patient-reported symptoms were directly compared between MAPP ML-derived phenotypic clusters to previously defined phenotypes from a single center (SC) cohort., Results: Unsupervised ML categorized IC/BPS participants into three phenotypes with distinct pain and urinary symptom patterns: myofascial pain, non-urologic pelvic pain, and bladder-specific pain. Defining characteristics included presence of myofascial pain or trigger points on examination for myofascial pain patients (p = 0.003) and bladder pain/burning for bladder-specific pain patients (p < 0.001). The three phenotypes were derived using only 11 features (fGUPI subscales and ICSI/ICPI items), in contrast to 49 items required previously. Despite substantial reduction in classification features, unsupervised ML independently generated similar symptomatic clusters in the MAPP cohort with equivalent symptomatic patterns and physical examination findings as the SC cohort., Conclusions: The reproducible identification of IC/BPS phenotypes, distinguishing bladder-specific pain from myofascial and genital pain, using independent ML analysis of a multicenter database suggests these phenotypes reflect true pathophysiologic differences in IC/BPS patients., (© 2024. The Author(s).)

Objectives: To determine the effect of intravesical onabotulinum toxin-A (BoNT-A) treatment on sexual functions in female patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS)., Methods: Female patients with IC/BPS refractory to previous treatments were included in the study between January 2020 and April 2022. Patients were treated with the trigone-sparing injection (Group 1) or trigone-included injection (Group 2) techniques. 100 Units of BoNT-A was applied submucosally on 20 different points. The patients were evaluated with visual analog scale (VAS), O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Female Sexual Function Index (FSFI) questionnaires, 3-day voiding diary, uroflowmetry, and post-voiding residual volume analysis in the preoperative period, as well as on the 30th and 90th days postoperatively. For the repeated measurements, analysis of variance was used to assess the time-dependent variation across groups., Results: The baseline FSFI score of the patients was 15.96 ± 3.82. Following the treatment, the FSFI scores were 22.43 ± 4.93 and 24.41 ± 5.94 on the 30th and 90th days, respectively (p < .001). We observed statistically significant improvement in all FSFI subdomains (p < .05). Statistically significant improvements with treatment on ICSI, ICPI, and VAS scores were achieved (p < .05). Preoperative FSFI scores were similar in Group 1 and Group 2 (p = .147). While the preoperative FSFI scores were 17.00 ± 3.73 and 14.84 ± 3.72 for Group 1 and Group 2, respectively, the scores after the treatment were 22.85 ± 5.01 and 21.98 ± 5.01 on the 30th day, and 24.62 ± 6.06 and 24.19 ± 6.05 on the 90th day postoperatively. Significant improvement was observed in FSFI scores with treatment, and no difference was observed between the two groups in terms of treatment response (p = .706)., Conclusions: Intravesical BoNT-A injection in the treatment of women with refractory IC/BPS improves sexual functions. It also significantly improves pain and symptom scores. Both trigone-sparing and trigone-including injections are similarly safe and effective., (© 2024 John Wiley & Sons Australia, Ltd.)

Introduction and Hypothesis: To evaluate the effect of AF219, a P2X3 receptor antagonist, in animal models of interstitial cystitis/bladder pain syndrome (IC/BPS) induced by cyclophosphamide (CYP) or water avoidance stress (WAS)., Methods: Thirty-two adult female Wistar albino rats were used in each IC/BPS model. Assessment of nociception and anxiety and severity of inflammation in the bladder were assessed by behavioral experiments and histopathological examinations respectively. The contraction responses of the bladder were evaluated in vitro and protein levels of P2X3, P2X7, Trk-A, TRPV1, and TRPA1 were analyzed by Western blot., Results: The IC/BPS groups had shorter response times to noxious stimuli, exhibited more anxiety-like behavior, had higher inflammation-based histological scores, and showed greater increased contraction responses to carbachol, adenosine triphosphate, and electrical field stimulation in in vitro bladder strips than controls for both models (p < 0.05). The improvements in behavioral and bladder contraction responses and inflammation scores in the IC/BPS + AF219 groups were similar to control findings (p > 0.05). Exposure to WAS or CYP increased P2X3 expression in the bladder compared with the controls (p < 0.05). Apart from TRPA1, the levels of P2X7, Trk-A, and TRPV1 were also higher in the IC/BPS groups than in the controls (p < 0.05). No significant differences were observed between IC/BPS + AF219 and controls regarding P2X3, P2X7, Trk-A, and TRPV1 in the WAS model (p > 0.05). Moreover, P2X3 and P2X7 levels were significantly lower in IC/BPS + AF219 than in the AF219-untreated WAS model (p < 0.05)., Conclusions: These findings suggest that P2X3 receptors play a significant role in bladder functional responses, nociception, and also the pathogenesis of IC/BPS. AF219 may be a promising therapeutic strategy for IC/BPS. Comparing AF219 with current IC/BPS treatment agents in future studies may yield valuable insights into its efficacy., (© 2024. The International Urogynecological Association.)

Purpose: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research., Materials and Methods: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals., Results: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms., Conclusions: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

Aim: To assess the quality of life of patients with interstitial cystitis (IC) and to study effective options used to control symptoms on outpatient basis., Materials and Methods: The results of a descriptive prospective cross-sectional cohort study are presented. The medical charts of patients who were treated in the City Clinical Hospital named after Spasokukotsky from 2021 to 2023 were analyzed. Eighty inpatient medical charts of various patients with a final diagnosis of IC with Hunner's lesion were identified. Only 53 patients were interviewed due to the inclusion/exclusion criteria. Respondents were asked to complete a survey consisting of 15 questions. The survey was carried out online for patients who did not require surgical treatment at the time of the study, and offline for patients admitted for repeated surgical treatment., Results: The average age of respondents was 59.011.1 years. 58% (31) of patients noted the presence of constant pain in the pelvic area during the day, while 85% (45) of patients reported pain outside the bladder area, in the urethra and perineum. The intensity of pain in the pelvic area was 4.9 (2.3-5.6) points. Higher pain scores 6.24 (5.8-9.0) were observed in 47% (25) of patients admitted for repeat surgical treatment. 62% (33) of patients had a titer of bacteria in a urine test above 104, while 51% (27) of patients experienced relief of symptoms after taking antibacterial drugs. For the treatment and symptomatic relief, the following are most often used: pentosan sodium polysulfate (26%, n=14), antibacterial drugs of the nitrofuran group (25%, n=13), amitriptyline (15%, n=8), non-steroidal anti-inflammatory drugs (11%, n=6) patients. 23% (12) of respondents received intravesical therapy. The time from the onset of symptoms to the final diagnosis was 48 (24-96) months., Conclusions: Although infection is a criterion for excluding the diagnosis of IC, more than 62% of patients have positive urine culture. The results obtained indicate the need to improve existing approaches to the diagnosis of IC, as well as to develop treatment algorithms for painful bladder syndrome to control symptoms.

Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases.

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic painful bladder condition characterized by pelvic pain and urinary symptoms without another identifiable cause. Cystoscopy as primary initial investigation for IC/BPS has not been accepted yet and needs more studies to definitely conclude., Aims and Objectives: We aimed to assess cystoscopy findings in patients of interstitial cystitis/bladder pain syndrome and to prove role of cystoscopy as primary initial investigation for interstitial cystitis/bladder pain syndrome., Materials and Methods: Our prospective observational study included 35 female patients aged 18-69 years presenting to the Urology OPD at SMS Hospital with suprapubic or pelvic pain for 6 months, bladder pain that worsens with bladder filling and reduced with voiding, dysuria, urinary frequency and urgency, nocturia, dyspareunia. Those with history of bladder capacity more than 350 ml, duration of symptoms less than 6 months, day time frequency less than eight times per day, diagnosis of bacterial cystitis or prostatitis, bladder or ureteral calculi, active genital herpes, any existing urological malignancy, radiation cystitis were excluded from the study. They were then subject to cystoscopy and the findings of the cystoscopy were analyzed., Results: Out of the 35 patients, 11 (31.43%) had a normal cystoscopy. Of the 24 patients (68.57%) who had a positive cystoscopy, cystoscopy in seven patients (20.0%) revealed an ulcer. All these seven patients underwent fulguration. In the remaining 17 patients the abnormal findings were petechiae, large submucosal bleed. The sensitivity of cystoscopy in detecting the ulcerative type of Interstitial cystitis was found to be 20.0%., Conclusion: Our study found that Cystoscopy, if employed in initial investigation can help early detection of ulcerative variety of IC/BPS and can act as therapeutic modality by using fulguration plus hydrodistension. Larger comparative studies are needed for diagnostic/Therapeutic value of cystoscopy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine real-world data regarding intravesical dimethyl sulfoxide (DMSO) therapy after official approval as a treatment for Hunner-type interstitial cystitis (HIC) in Japan., Methods: This single institution, retrospective observational study was conducted between 2021 and 2022 to evaluate the outcomes of 30 patients with refractory HIC who received intravesical DMSO therapy according to the approved standardized regimen: administration of DMSO every 2 weeks for a total of 12 weeks. Treatment outcomes were evaluated using a 7-graded global response assessment scale, O'Leary and Sant's symptom and problem indices (OSSI/OSPI), the overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, quality of life (QOL) score, and frequency volume chart variables. Related complications were also documented., Results: The response rates at 2, 4, 6, 8, 10, and 12 weeks were 36.7%, 43.3%, 53.3%, 60.0%, 70.0%, and 70.0%, respectively. Compared with baseline, OSSI/OSPI, pain intensity, urinary frequency, and the QOL score improved significantly from 4 weeks of treatment. The OABSS score and functional bladder capacity also showed a tendency toward moderate improvement, but the difference was not significant. The mean duration of symptom relapse after termination of treatment was 6.4 ± 3.9 months. No patients discontinued treatment due to adverse events, although acute bladder irritation during infusion was noted in 21 patients (70%), which disappeared within 3 days., Conclusions: This study verifies the safety, moderately durable efficacy, and tolerability of the standard intravesical treatment with DMSO for HIC in Japan., (© 2023 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

We analyzed the symptoms composition of Interstitial Cystitis (IC), the regularity of the evolution of symptoms before and after treatment, and the visualization of the community network, to provide a reference for clinical diagnosis and treatment of Interstitial Cystitis. Based on the outpatient electronic case data of 552 patients with Interstitial Cystitis, we used a complex network community discovery algorithm, directed weighted complex network, and Sankey map to mine the data of the symptoms composition of Interstitial Cystitis, the evolution of symptoms before and after treatment and the visualization of the community network, to analyze the epidemiological characteristics of interstitial cystitis symptoms in the real world. By the community division of the complex network of interstitial cystitis symptoms, We finally obtained three core symptom communities. Among them, symptom community A (bladder-related symptoms) is the symptom community with the highest proportion of nodes (60.00%) in the complex network of Interstitial Cystitis, symptom community B (non-bladder-related symptoms 1) ranks second (32.00%) in a complex network of Interstitial Cystitis, and symptom community C (non-bladder-related symptoms 2) has the lowest proportion (8.00%). There is a complex evolutionary relationship between the symptoms of Interstitial Cystitis before and after treatment. Among the single symptoms before and after treatment, the decreased rate of Day frequency is 93.22%, and the reduced urgency rate is 93.07%. The decline rate of Nocturia was 82.33%. From the perspective of different communities, the overall symptoms of symptom community A decreased by 34.39% after treatment, the general symptoms of symptom community B decreased by 35.37%, and the prevalent symptoms of symptom community C decreased by 71.43%. In the case of using diet regulation treatment to treat bladder pain, the cure rate of bladder pain can reach 22.67%. The cure rate of burning in bladders can get 15.38% with Percutaneous Sacral neuromodulation, 96.95% with diet regulation treatment, and 100% with Percutaneous Sacral neuromodulation. When using behavioral physiotherapy to treat bladder pain, 3.57% of the patient's symptoms change to bladder discomfort; 4% of the patient's symptoms change to bladder discomfort when using oral medicine to treat bladder pain.Symptom research methods based on community findings can effectively explore the rule of symptom outcome of Interstitial Cystitis before and after treatment, and the results are highly interpretable by professionals. The cover image is based on the Original Article Research on symptoms composition, time series evolution, and network visualisation of interstitial cystitis based on complex network community discovery algorithm by Lei Pang et al., https://doi.org/10.1049/syb2.12083., (© 2023 The Authors. IET Systems Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)