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Keywords = interstitial cystitis/bladder pain syndrome (IC/BPS)

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15 pages, 935 KB  
Article
Transurethral Injection of Autologous Micronized Adipose Tissue for Refractory Interstitial Cystitis/Bladder Pain Syndrome: A Retrospective Pilot Study
by Mauro Cervigni, Alice Antonioni, Manfredi Bruno Sequi, Andrea Fuschi, Yazan Al Salhi, Fabio Maria Valenzi, Paolo Pietro Suraci, Antonio Carbone and Antonio Luigi Pastore
Biomedicines 2026, 14(5), 1119; https://doi.org/10.3390/biomedicines14051119 - 15 May 2026
Cited by 1 | Viewed by 565
Abstract
Background/Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by pelvic pain, urinary symptoms, and reduced quality of life, with limited effective treatment options. Regenerative approaches using adipose-derived mesenchymal stromal cells (MSCs) have shown promising preclinical results. This study aimed [...] Read more.
Background/Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by pelvic pain, urinary symptoms, and reduced quality of life, with limited effective treatment options. Regenerative approaches using adipose-derived mesenchymal stromal cells (MSCs) have shown promising preclinical results. This study aimed to evaluate the feasibility, safety, and preliminary efficacy of transurethral implantation of autologous micronized adipose tissue (MAT) in patients with refractory IC/BPS. Methods: We conducted a single-center retrospective observational pilot study including 20 patients with refractory IC/BPS treated between April and October 2024. Adipose tissue was harvested via liposuction and mechanically processed using a closed system (Matrigen device) to obtain minimally manipulated micronized adipose tissue. The product was injected transurethrally into the bladder submucosa. Patients were evaluated at baseline and at 1, 3, and 6 months using validated questionnaires (ICSI/ICPI, SF-36, MOS Sexual Function), verbal rating scale (VRS) for pain and urgency, urodynamic parameters, and cystoscopic findings. Changes over time were assessed using paired non-parametric tests. Results: At 6 months, 65% of patients met responder criteria, defined as ≥50% improvement in pain and/or urgency or a positive global response. Significant improvements were observed in IC Problem Index, SF-36, MOS scores, and VRS urgency, while VRS pain improved significantly at 6 months. Urodynamic parameters showed increased bladder capacity (median 275 to 325 mL, p < 0.001) and reduced post-void residual volume (80 to 40 mL, p < 0.001). Cystoscopic findings demonstrated improvement in bladder mucosal appearance. The procedure was well tolerated, with no serious adverse events or immunological complications observed. Conclusions: In this exploratory pilot study, transurethral implantation of autologous micronized adipose tissue was associated with improvements in symptoms, bladder function, and cystoscopic findings in patients with refractory IC/BPS. These results support the feasibility and potential role of minimally manipulated adipose-derived therapies in this setting. Given the small sample size and absence of a control group, findings should be considered exploratory. Larger controlled studies are warranted to confirm efficacy and evaluate long-term outcomes. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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31 pages, 505 KB  
Review
From Regenerative Mechanisms to Clinical Practice: Current Status, Controversies, and Future Perspectives of Platelet-Rich Plasma in Urology and Sexual Medicine
by Rui Qu, Jiaqi Gu, Yi Luo, Luo Yang and Yi Dai
J. Clin. Med. 2026, 15(8), 2949; https://doi.org/10.3390/jcm15082949 - 13 Apr 2026
Cited by 1 | Viewed by 1159
Abstract
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, [...] Read more.
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, neuroregeneration, immune modulation, and tissue remodeling. However, clinical uptake has outpaced high-quality evidence, while heterogeneity in PRP preparation, characterization, and delivery limits interpretability and reproducibility. This structured narrative review aims to critically integrate mechanistic, preclinical, and clinical evidence regarding PRP use in ED, Peyronie’s disease (PD), stress urinary incontinence (SUI), interstitial cystitis/bladder pain syndrome (IC/BPS), and selected emerging indications. We further aim to identify sources of heterogeneity and propose an actionable minimum reporting framework (PRP-Uro Checklist) to guide future research. Methods: A structured search of PubMed/MEDLINE was conducted for studies published between 2021 and 2025. The relevant literature on PRP use in ED, PD, SUI, IC/BPS, and related indications was included for critical narrative synthesis. Emphasis was placed on PRP classification and preparation variables, outcome measure validity, and sources of heterogeneity across studies. Results: Mechanistic and preclinical evidence supports PRP’s potential to modulate nerve repair, angiogenesis, extracellular matrix remodeling, and immune polarization through a complex secretome of growth factors, cytokines, and extracellular vesicles (EVs). Clinical evidence suggests that intracavernosal PRP may improve erectile function in selected populations, but effect size, durability, and superiority over placebo remain uncertain due to small trials, substantial placebo effects, short follow-up, and incomplete biologic characterization. Evidence for PRP in PD, SUI, and IC/BPS remains preliminary and is derived largely from small cohorts, proof-of-concept studies, or uncontrolled designs, although early findings suggest potential symptom benefit and acceptable short-term tolerability. Across indications, inconsistent PRP reporting, particularly the absence of absolute platelet dose, leukocyte quantification, activation method, and standardized treatment protocols, represents a major barrier to reproducibility and evidence synthesis. Conclusions: PRP is biologically plausible and appears broadly safe, but its role in urology and sexual medicine remains investigational and is not yet supported by guideline-level evidence. To enhance reproducibility and interpretation, we propose a Minimum PRP Reporting Checklist for Urology and Sexual Medicine Trials (PRP-Uro Checklist). Future progress requires rigorous standardized reporting, indication-specific biologic characterization, rigorously designed sham-controlled trials, clinically meaningful endpoints, and longer-term follow-up. Full article
(This article belongs to the Section Nephrology & Urology)
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12 pages, 343 KB  
Article
Therapeutic Efficacy of Different Bladder Monotherapies Versus Multimodal Therapy in Patients with Interstitial Cystitis/Bladder Pain Syndrome
by Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang and Hann-Chorng Kuo
Biomedicines 2026, 14(4), 834; https://doi.org/10.3390/biomedicines14040834 - 6 Apr 2026
Viewed by 853
Abstract
Purpose: This study compared the therapeutic efficacy of different bladder monotherapies and multimodal therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and methods: In total, 190 patients with a confirmed diagnosis of IC/BPS were treated with different bladder therapies. [...] Read more.
Purpose: This study compared the therapeutic efficacy of different bladder monotherapies and multimodal therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and methods: In total, 190 patients with a confirmed diagnosis of IC/BPS were treated with different bladder therapies. The bladder monotherapies included intravesical platelet-rich plasma (PRP) injection (n = 60), intravesical botulinum toxin A (BoNT-A) injection (n = 33), intravesical hyaluronic acid (HA) instillation (n = 36), and low-energy shock wave (LESW) bladder therapy (n = 61). Multimodal therapy (MMT) was provided to patients who had unsuccessful initial bladder treatment targeting chronic inflammation, urothelial dysfunction, bladder pain, pelvic floor muscle pain, psychological stress, and lower urinary tract dysfunction. The treatment outcome was assessed using self-reported Global Response Assessment scores at 3 months and during the follow-up time points after bladder treatment. Results: Thirty-one patients received MMT. The 3-month success rates of bladder therapy were 55.0% for PRP injection, 57.6% for BoNT-A injection, 50.0% for HA instillation, 46.7% for LESW bladder therapy, and 58.1% for MMT. The success rates of bladder monotherapy decreased after 6 months. However, the success rate of MMT increased at 9 (67.7%) and 12 (73.1%) months. Patients treated with MMT exhibited improvement in glomerulation grade after cystoscopic hydrodistention. Only patients with successful treatment outcomes after MMT had improvement in bladder pain severity and pelvic floor muscle pain parameters. Conclusions: Bladder monotherapy such as PRP injection, BoNT-A injection, HA instillation, and LESW bladder therapy had successful treatment outcomes in patients with IC/BPS. In patients who had unsuccessful initial bladder therapy, the 3-month success rate of MMT was 58.1% and sustained improvement with time, particularly in the improvement of bladder pain and PFM pain severity. Full article
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14 pages, 1821 KB  
Review
Advances in Cytokines and Inflammatory Mechanisms in the Pathogenesis of Interstitial Cystitis/Bladder Pain Syndrome
by Yulin Xiao, Donglin Zhu and Xiangfu Zhou
Biomolecules 2026, 16(1), 138; https://doi.org/10.3390/biom16010138 - 13 Jan 2026
Cited by 3 | Viewed by 2607
Abstract
Bladder discomfort, urgency, and frequency of urination are the hallmarks of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic illness. Although the precise etiology remains unclear, numerous clinical investigations have established inflammation as a pivotal factor in its pathogenesis, encompassing uroepithelial damage, mast cell [...] Read more.
Bladder discomfort, urgency, and frequency of urination are the hallmarks of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic illness. Although the precise etiology remains unclear, numerous clinical investigations have established inflammation as a pivotal factor in its pathogenesis, encompassing uroepithelial damage, mast cell activation, and neuroinflammatory responses. This review delineates the pathological features and classification of IC/BPS, emphasizing the contribution of inflammatory mechanisms and the involvement of cytokines as key mediators in disease progression. The insights presented aim to guide the advancement of innovative treatment approaches. Full article
(This article belongs to the Section Molecular Biomarkers)
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14 pages, 1779 KB  
Article
Pilot Proteomic Analysis of Urinary Extracellular Vesicles Supports the “Toxic Urine Hypothesis” as a Vicious Cycle in Refractory IC/BPS Pathogenesis
by Man-Jung Hung, Evelyn Yang, Tsung-Ho Ying, Peng-Ju Chien, Ying-Ting Huang and Wen-Wei Chang
Int. J. Mol. Sci. 2026, 27(1), 130; https://doi.org/10.3390/ijms27010130 - 22 Dec 2025
Viewed by 2183
Abstract
Despite treatments such as pentosan polysulfate, hyaluronic acid, botulinum toxin A, and platelet-rich plasma, many interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience persistent symptoms. Urinary extracellular vesicles (uEVs) carry molecular cargo reflecting disease pathophysiology, yet their proteomic profiles in treated IC/BPS remain unexplored. [...] Read more.
Despite treatments such as pentosan polysulfate, hyaluronic acid, botulinum toxin A, and platelet-rich plasma, many interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience persistent symptoms. Urinary extracellular vesicles (uEVs) carry molecular cargo reflecting disease pathophysiology, yet their proteomic profiles in treated IC/BPS remain unexplored. This pilot study examined uEV proteomics in refractory IC/BPS cases to test the “Toxic Urine Hypothesis”—a vicious cycle, whereby urothelial dysfunction enables EV-mediated toxin penetration, triggering inflammation that further impairs the bladder barrier. Urinary EVs were isolated from six female IC/BPS patients on active treatments and four healthy female controls. Mass spectrometry-based proteomics identified differential protein expressions, followed by pathway enrichment analysis and functional validation using NF-κB reporter assays in HEK293T cells and Western blot in primary human bladder epithelial cells. IC/BPS EVs exhibited 31 upregulated proteins (including HPGD, KRT8, HSPA4, 14-3-3 family members) and 19 downregulated proteins (including neutrophil granule proteins MPO and ELANE), indicating suppressed acute neutrophil inflammation but enriched homeostatic, metabolic, and regenerative pathways. Patient EVs induced significantly higher NF-κB activation than in the controls, with upregulated 14-3-3ζ and phosphorylated NF-κB p65 in bladder epithelial cells. These findings support the “Toxic Urine Hypothesis”, revealing persistent NF-κB-mediated chronic epithelial stress despite suppressed acute inflammation in treated IC/BPS patients, suggesting that therapies targeting inflammation and regeneration may help break this vicious cycle. Full article
(This article belongs to the Special Issue Role of Extracellular Vesicles in Diseases)
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20 pages, 1755 KB  
Review
Application of Platelet-Rich Plasma in Gynaecologic Disorders: A Scoping Review
by Nadia Willison, Fariba Behnia-Willison, Pouria Aryan, Zahra Ali Padhani, Negin Mirzaei Damabi, Tran Nguyen, Johnny Yi, Rituparna Dutta and Derek Abbott
J. Clin. Med. 2025, 14(16), 5832; https://doi.org/10.3390/jcm14165832 - 18 Aug 2025
Cited by 3 | Viewed by 8220
Abstract
Platelet-rich plasma (PRP) therapy is a non-invasive, autologous treatment with regenerative potential in gynaecology beyond fertility applications. This review evaluates PRP in non-fertility-related gynaecological conditions affecting women’s quality of life (QoL). Methods: Following PRISMA-ScR guidelines, we searched Embase, CINAHL, Web of Science, Scopus, [...] Read more.
Platelet-rich plasma (PRP) therapy is a non-invasive, autologous treatment with regenerative potential in gynaecology beyond fertility applications. This review evaluates PRP in non-fertility-related gynaecological conditions affecting women’s quality of life (QoL). Methods: Following PRISMA-ScR guidelines, we searched Embase, CINAHL, Web of Science, Scopus, CENTRAL, and MEDLINE for studies on PRP in conditions such as vulvar lichen sclerosus (VLS), vulvovaginal atrophy (VVA), sexual dysfunction (SD), stress urinary incontinence (SUI), and interstitial cystitis/bladder pain syndrome (IC/BPS). Of 3660 records screened, 43 studies (randomised controlled trials, quasi-experimental, cohort, and case series) were included. Results: PRP improved symptoms and QoL in several conditions, particularly VLS and SD, and was generally well tolerated with minor adverse effects (e.g., injection-site pain, transient discomfort). Evidence for abnormal uterine bleeding (AUB) and pelvic organ prolapse (POP) was inconclusive. Considerable heterogeneity in preparation protocols and outcome measures limited cross-study comparison. Conclusions: PRP shows promise as a minimally invasive therapy for certain gynaecological conditions. Standardisation of preparation and administration, along with large-scale RCTs, is needed to determine long-term efficacy and safety. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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19 pages, 3569 KB  
Article
Bladder p75NTR-Mediated Anti-Inflammatory Response via the TLR4/TRAF6/NF-κB Axis
by Claudia Covarrubias, Abubakr H. Mossa, Laura R. Yan, Benjamin Desormeau, Philippe G. Cammisotto, H. Uri Saragovi and Lysanne Campeau
Life 2025, 15(6), 957; https://doi.org/10.3390/life15060957 - 14 Jun 2025
Viewed by 4251
Abstract
Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75NTR. The aim of the presented study was to assess whether [...] Read more.
Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75NTR. The aim of the presented study was to assess whether p75NTR antagonist THX-B can modulate LPS-mediated inflammation in bladder cells. In vitro expression and LPS-activation of p75NTR were confirmed in urothelial (URO) and smooth muscle (SMC) cells. In UROs, p75NTR antagonism abolished the LPS-elicited rise in membrane-bound and soluble TNF-α. However, it could not prevent LPS-induced rise in phosphorylated ERK nor decrease in phosphorylated p38MAPK, nor the increase in iNOS and nitric oxide (NO) content. On the other hand, in SMCs, LPS increased phosphorylation of JNK, nuclear translocation of NF-κB, and association of TRAF6 to p75NTR, outcomes prevented by p75NTR antagonism. In UROs, LPS decreased the expression of tight junction proteins, ZO-1 and occludin, with the latter rescued by p75NTR antagonism. Intraurethral instillation of LPS increased inflammation in the lamina propria, activation of JNK, and contractile activity of bladder tissue. Alternatively, intraperitoneal THX-B injections prevented LPS-induced inflammation but not enhanced muscle contraction. Our results suggest that inhibition of p75NTR could help in reducing bladder symptoms during cystitis. Full article
(This article belongs to the Section Microbiology)
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23 pages, 8576 KB  
Article
Pterostilbene Reduces Cyclophosphamide-Induced Interstitial Cystitis by Facilitating Nrf2 Activation and Suppressing the NLRP3 Inflammasome Pathway
by Jiong Zhang, Jipeng Wang, Xinhao Wang, Zehao Yan, Lingfeng Meng and Yaoguang Zhang
Int. J. Mol. Sci. 2025, 26(12), 5490; https://doi.org/10.3390/ijms26125490 - 8 Jun 2025
Cited by 11 | Viewed by 2845
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) causes significant discomfort in patients and impairs the quality of urination. Pterostilbene (PTE), a natural polyphenol antioxidant, has demonstrated beneficial effects in mitigating inflammation, enhancing antioxidant capacity, and ameliorating organ dysfunction in various chronic nonspecific inflammatory conditions. The [...] Read more.
Interstitial cystitis/bladder pain syndrome (IC/BPS) causes significant discomfort in patients and impairs the quality of urination. Pterostilbene (PTE), a natural polyphenol antioxidant, has demonstrated beneficial effects in mitigating inflammation, enhancing antioxidant capacity, and ameliorating organ dysfunction in various chronic nonspecific inflammatory conditions. The aim of this study was to evaluate the efficacy of PTE in IC/BPS and elucidate its underlying mechanisms using a rat model of cyclophosphamide (CYP)-induced interstitial cystitis. In comparison, chronic pain progression, histopathological features, and cytokine levels demonstrated that PTE mitigated the severity of symptoms in CYP-induced rats by inhibiting the NLRP3 inflammasome in a dose-dependent manner. Further mechanistic investigations indicated that PTE intervention alleviated oxidative stress in CYP-induced IC in rats via activation of the Nrf2/HO-1 signaling pathway. Moreover, inhibitors of the Nrf2/HO-1 pathway effectively blocked PTE-mediated attenuation of oxidative stress. The suppression of NLRP3 inflammasome activation by PTE could also be reversed by inhibition of the Nrf2/HO-1 pathway. In vitro studies revealed that PTE enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and suppressed NLRP3 inflammasome activation in SV-HUC-1 cells exposed to lipopolysaccharide (LPS) and Adenosine Triphosphate (ATP). These findings collectively suggest that PTE treatment inhibits oxidative stress and suppresses NLRP3 inflammasome activation through modulation of the Nrf2/HO-1 pathway. Full article
(This article belongs to the Section Molecular Immunology)
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11 pages, 433 KB  
Article
Exploring the Efficacy of Vessilen® in Treating Bladder Pain Syndrome/Interstitial Cystitis: A Prospective Study
by Mariachiara Palucci, Marta Barba, Alice Cola and Matteo Frigerio
Healthcare 2025, 13(11), 1340; https://doi.org/10.3390/healthcare13111340 - 4 Jun 2025
Cited by 1 | Viewed by 3321
Abstract
Background/Objectives: Bladder pain syndrome (BPS), or painful bladder syndrome (PBS)/interstitial cystitis (IC), is a chronic inflammatory condition characterized by symptoms like pain, urgency, urinary incontinence, and sometimes urinary retention, which significantly affect patients’ quality of life. The etiology of PBS/IC remains unclear and [...] Read more.
Background/Objectives: Bladder pain syndrome (BPS), or painful bladder syndrome (PBS)/interstitial cystitis (IC), is a chronic inflammatory condition characterized by symptoms like pain, urgency, urinary incontinence, and sometimes urinary retention, which significantly affect patients’ quality of life. The etiology of PBS/IC remains unclear and may be multifactorial, with no definitive treatment currently available. The challenge lies in finding new therapeutic strategies. Various intravesical treatments, such as heparin, hyaluronic acid, and botulinum toxin, are commonly used for PBS/IC. In this study, we aimed to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation consisting of 2% adelmidrol and 0.1% sodium hyaluronate) in patients with IC/PBS or other bladder disorders. Methods: This was a pilot study conducted at a tertiary-level urogynecology center. Two validated questionnaires were administered to patients before and after treatment: the Visual Analogue Scale (VAS) and the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS Long Form). The Patient Global Impression (PGI) scale was used to assess symptom severity. Results: Among the 25 patients who completed six weekly instillations, a significant decrease in bladder symptoms was observed, as indicated by both the ICIQ-FLUTS scale (89.3 vs. 61.3; p = 0.021) and VAS score (4.4 vs. 2.6; p < 0.001). Additionally, 80% of patients reported symptom improvement (PGI-I score ≤ 3). Conclusions: Intravesical Vessilen® (adelmidrol + sodium hyaluronate) appears to be an innovative therapeutic approach for PBS/IC and other chronic inflammatory bladder disorders due to its anti-inflammatory and antinociceptive properties. Full article
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13 pages, 1344 KB  
Article
Long-Term Outcomes of Sacral Neuromodulation for Refractory Interstitial Cystitis/Bladder Pain Syndrome: A Retrospective Cohort Study
by Martina Rekatsina, Matteo Luigi Giuseppe Leoni, Veerle Visser-Vandewalle, Marco Mercieri, Giustino Varrassi and Georgios Matis
J. Clin. Med. 2025, 14(11), 3647; https://doi.org/10.3390/jcm14113647 - 22 May 2025
Cited by 6 | Viewed by 5871
Abstract
Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by persistent bladder-related pain and urinary symptoms, often refractory to conventional treatments. Sacral neuromodulation (SNM) has emerged as a promising therapeutic option for managing refractory IC/BPS. Methods: This retrospective study [...] Read more.
Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by persistent bladder-related pain and urinary symptoms, often refractory to conventional treatments. Sacral neuromodulation (SNM) has emerged as a promising therapeutic option for managing refractory IC/BPS. Methods: This retrospective study included 24 patients with IC/BPS treated with SNM between 2017 and 2022. Baseline and follow-up data were collected on pain, opioid use, urinary symptoms, and quality of life. Patients underwent a trial of tonic stimulation before permanent implantation. Continuous variables were reported as median (IQR) and categorical data as counts and percentages. Pre- and post-SNM differences were analyzed using the Wilcoxon rank-sum test. Kaplan–Meier analysis evaluated lead survival, and a Sankey diagram illustrated employment status transitions. Results: Patients had a median age of 54.5 years (IQR: 47–61), with 92% female. Subtypes included Type 1 IC/BPS (8.3%), Type 2 (45.8%), Type 3 (37.6%), and unknown type (8.3%). Median pain duration was 4.5 years (IQR: 3–7.3). SNM resulted in significant improvements in pain (NRS: baseline 8 [IQR: 8–9], last follow-up 3 [IQR: 2–4], p < 0.0001), opioid use (MME: baseline 20 [IQR: 10–40], last follow-up 0 [IQR: 0–10], p < 0.0001), urinary function (24-h voids: baseline 19 [IQR: 14.5–25.8], last follow-up 8 [IQR: 6–12], p < 0.0001), and quality of life (QOL) (EQ-5D-5L: baseline 0.50 [IQR: 0.36–0.56], last follow-up 0.83 [IQR: 0.76–0.89], p < 0.0001). Employment rates increased from 43.5% to 50%, and unemployment decreased from 8.7% to 4.2%. The median follow-up was 35 months (IQR: 28–53). Conclusions: SNM significantly improved pain, urinary symptoms, quality of life, and employment outcomes in patients with refractory IC/BPS. These findings highlight its efficacy as a minimally invasive and reversible option for managing this challenging condition. Full article
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13 pages, 1046 KB  
Article
Applying K-Means Cluster Analysis to Urinary Biomarkers in Interstitial Cystitis/Bladder Pain Syndrome: A New Perspective on Disease Classification
by Yuan-Hong Jiang, Jia-Fong Jhang, Jen-Hung Wang, Ya-Hui Wu and Hann-Chorng Kuo
Int. J. Mol. Sci. 2025, 26(8), 3712; https://doi.org/10.3390/ijms26083712 - 14 Apr 2025
Cited by 1 | Viewed by 1698
Abstract
This study applied K-means cluster analysis to urinary biomarker profiles in interstitial cystitis/bladder pain syndrome (IC/BPS) patients, aiming to provide a new perspective on disease classification and its clinical relevance. We retrospectively analyzed urine samples from 127 IC/BPS patients and 30 controls. The [...] Read more.
This study applied K-means cluster analysis to urinary biomarker profiles in interstitial cystitis/bladder pain syndrome (IC/BPS) patients, aiming to provide a new perspective on disease classification and its clinical relevance. We retrospectively analyzed urine samples from 127 IC/BPS patients and 30 controls. The urinary levels of 10 inflammatory cytokines and three oxidative stress markers (8-hydroxy-2-deoxyguanosin [8-OHdG], 8-isoprostane, and total antioxidant capacity [TAC]) were quantified. K-means clustering was performed to identify biomarker-based patient subgroups. IC/BPS patients exhibited significantly elevated urinary levels of Eotaxin, MCP-1, NGF, 8-OHdG, 8-isoprostane, and TAC compared to controls (all p < 0.05). K-means clustering identified four distinct subgroups. Cluster 4, characterized by the highest levels of inflammatory and oxidative stress biomarkers, comprised 85% ESSIC type 2 IC/BPS patients and exhibited the lowest visual analogue scale (VAS) pain scores and maximal bladder capacity (MBC). Correlation analysis revealed distinct cluster-specific associations between biomarker levels and clinical parameters, including the VAS pain score, MBC, the grade of glomerulation, and treatment outcomes. Applying K-means clustering to urinary inflammatory and oxidative stress biomarkers provides a new perspective on disease classification, identifying IC/BPS subtypes with distinct clinical and biochemical characteristics. This approach may refine disease phenotyping and guide personalized treatment strategies in the future. Full article
(This article belongs to the Special Issue Machine Learning in Disease Diagnosis and Treatment)
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16 pages, 1598 KB  
Article
Clustering of Urinary Biomarkers to Identify Interstitial Cystitis Subtypes and Different Clinical Characteristics and Treatment Outcomes
by Jing-Hui Tian, Chung-You Tsai, Wan-Ru Yu, Yuan-Hong Jiang, Jia-Fong Jhang and Hann-Chorng Kuo
Biomedicines 2025, 13(2), 369; https://doi.org/10.3390/biomedicines13020369 - 5 Feb 2025
Cited by 9 | Viewed by 3576
Abstract
Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is mysterious and difficult to diagnose without cystoscopic hydrodistention. This study aimed to explore non-invasive and highly reliable urine biomarkers to identify Hunner’s IC (HIC) and different non-Hunner’s IC (NHIC) subtypes. Methods: In total, 422 women with [...] Read more.
Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is mysterious and difficult to diagnose without cystoscopic hydrodistention. This study aimed to explore non-invasive and highly reliable urine biomarkers to identify Hunner’s IC (HIC) and different non-Hunner’s IC (NHIC) subtypes. Methods: In total, 422 women with and without clinically diagnosed IC/BPS (n = 376 and 46, respectively) were retrospectively enrolled. Patients were diagnosed with HIC or NHIC by cystoscopic hydrodistention under anesthesia. Then, the maximal bladder capacity (MBC) and glomerulation grade were determined. Thirteen urine inflammatory cytokines, chemokines, and oxidative stress biomarkers based on the previously reported predictors of IC/BPS were assayed using commercial microsphere kits. The dataset was randomly divided into training (70%) and test (30%) sets for model construction and validation using logistic regression and stepwise variable selection techniques. To construct the predictive models, univariate analysis was performed to evaluate the discriminative power of each urinary biomarker, measured by the area under the curve (AUC). Biomarkers with AUC values < 0.6 were excluded from further modeling. Multivariate logistic regression was then employed, with variables selected through stepwise forward selection based on log-likelihood criteria. For dichotomization, cutoff values were determined using quartile ranges from the control group. The final model’s performance was assessed using AUC, accuracy, sensitivity, and specificity in both training and test sets. Results: By setting the screening criterion to AUC ≥ 0.60, the potential urinary biomarkers for identifying IC/BPS cases were eotaxin, monocyte chemoattractant protein-1, tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoprostane. Those for identifying HIC from the IC/BPS cohort were interleukin (IL)-6, IL-8, interferon γ-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). A diagnostic algorithm using a cluster of urinary biomarkers included TNF-α ≥ 0.95 pg/mL or 8-OHDG ≥ 22.34 pg/mL and 8-isoprastane ≥ 22.34 pg/mL for identifying IC/BPS from the overall cohort; for identifying HIC from the IC/BPS cohort, the urinary IP-10 ≥ 3.74 pg/mL or IP-10 ≥ 19.94 pg/mL was added. Conclusions: Using a cluster of urinary biomarkers such as TNF-α or 8-OHdG and 8-isoprostane can identify IC/BPS from a study cohort, and adding the urinary IP-10 can distinguish HIC from IC/BPS cases. Full article
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13 pages, 1956 KB  
Article
Advancing Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) Diagnosis: A Comparative Analysis of Machine Learning Methodologies
by Joseph J. Janicki, Bernadette M. M. Zwaans, Sarah N. Bartolone, Elijah P. Ward and Michael B. Chancellor
Diagnostics 2024, 14(23), 2734; https://doi.org/10.3390/diagnostics14232734 - 5 Dec 2024
Cited by 8 | Viewed by 2564
Abstract
Background/Objectives. This study aimed to improve machine learning models for diagnosing interstitial cystitis/bladder pain syndrome (IC/BPS) by comparing classical machine learning methods with newer AutoML approaches, utilizing biomarker data and patient-reported outcomes as features. Methods. We applied various machine learning techniques to biomarker [...] Read more.
Background/Objectives. This study aimed to improve machine learning models for diagnosing interstitial cystitis/bladder pain syndrome (IC/BPS) by comparing classical machine learning methods with newer AutoML approaches, utilizing biomarker data and patient-reported outcomes as features. Methods. We applied various machine learning techniques to biomarker data from the previous IP4IC and ICRS studies to predict the presence of IC/BPS, a disorder impacting the urinary bladder. Data were sourced from two nationwide, crowd-sourced collections of urine samples involving 2009 participants. The models utilized included logistic regression, support vector machines, random forests, k-nearest neighbors, and AutoGluon. Results. Expanding the dataset for model training and evaluation resulted in improved performance metrics compared to previously published findings. The implementation of AutoML methods yielded enhancements in model accuracy over classical techniques. The top-performing models achieved a receiver-operating characteristic area under the curve (ROC-AUC) of up to 0.96. Conclusions. This research demonstrates an improvement in model performance relative to earlier studies, with the top model for binary classification incorporating objective urinary biomarker levels. These advancements represent a significant step toward developing a reliable classification model for the diagnosis of IC/BPS. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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15 pages, 2721 KB  
Article
Does Muscle Pain Induce Alterations in the Pelvic Floor Motor Unit Activity Properties in Interstitial Cystitis/Bladder Pain Syndrome? A High-Density sEMG-Based Study
by Monica Albaladejo-Belmonte, Michael Houston, Nicholas Dias, Theresa Spitznagle, Henry Lai, Yingchun Zhang and Javier Garcia-Casado
Sensors 2024, 24(23), 7417; https://doi.org/10.3390/s24237417 - 21 Nov 2024
Cited by 4 | Viewed by 2946
Abstract
Several studies have shown interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition that poses challenges in both diagnosis and treatment, is associated with painful pelvic floor muscles (PFM) and altered neural drive to these muscles. However, its pathophysiology could also involve other alterations [...] Read more.
Several studies have shown interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition that poses challenges in both diagnosis and treatment, is associated with painful pelvic floor muscles (PFM) and altered neural drive to these muscles. However, its pathophysiology could also involve other alterations in the electrical activity of PFM motor units (MUs). Studying these alterations could provide novel insights into IC/BPS and help its clinical management. This study aimed to characterize PFM activity at the MU level in women with IC/BPS and pelvic floor myalgia using high-density surface electromyography (HD-sEMG). Signals were recorded from 15 patients and 15 healthy controls and decomposed into MU action potential (MUAP) spike trains. MUAP amplitude, firing rate, and magnitude-squared coherence between spike trains were compared across groups. Results showed that MUAPs had significantly lower amplitudes during contractions on the patients’ left PFM, and delta-band coherence was significantly higher at rest on their right PFM compared to controls. These findings suggest altered PFM tissue and neuromuscular control in women with IC/BPS and pelvic floor myalgia. Our results demonstrate that HD-sEMG can provide novel insights into IC/BPS-related PFM dysfunction and biomarkers that help identify subgroups of IC/BPS patients, which may aid their diagnosis and treatment. Full article
(This article belongs to the Special Issue Advances in Electrophysiology Monitoring and Analysis)
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15 pages, 1235 KB  
Review
The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome
by Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang and Hann-Chorng Kuo
Biomedicines 2024, 12(9), 2051; https://doi.org/10.3390/biomedicines12092051 - 10 Sep 2024
Cited by 27 | Viewed by 17639
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due [...] Read more.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient’s needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition. Full article
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