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Background: The correlation between gut microbiota and interstitial cystitis has garnered significant attention in previous studies. Nevertheless, the causal relationship between them remains to be clarified. Methods: Genetic variation serves as a tool in Mendelian randomization analyses, facilitating the inference of causal relationships between exposure factors and disease outcomes. In this study, summary statistics derived from a comprehensive genome-wide association study conducted by the MiBioGen consortium were utilized as exposure factors, while interstitial cystitis data sourced from the GWAS Catalog served as the disease outcome. Then, a twosample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis. Results: IVW results confirmed that genus Haemophilus (OR = 2.20, 95% CI: 1.16- 4.15, p = 0.015), genus Butyricimonas (OR = 2.26, 95% CI: 1.15-4.45, p = 0.018), genus Bacteroides (OR = 4.27, 95% CI: 1.36-13.4, p = 0.013) and Coprococcus1 (OR = 3.39, 95% CI: 1.28-8.99, p = 0.014) had a risk effect on interstitial cystitis. Sensitivity analysis did not find outlier SNPs. Conclusion: Our analysis has identified a causal relationship between specific genera and interstitial cystitis. However, further validation through randomized controlled trials is essential to substantiate these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 × 107 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. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and safety of modified botulinum toxin type A (BoNT-A) injections (with additional periurethral injection [PUI] of BoNT-A) for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). This single-center, retrospective cohort study included 52 adult female patients with IC/BPS, with 24 patients receiving conventional BoNT-A injections and 28 receiving modified BoNT-A injections. The primary outcome measure was patient-reported global response assessment. Secondary outcomes included daytime frequency, nocturia, number of urinary urgency episodes in the voiding diary, pain visual analog score, O′Leary–Sant interstitial cystitis symptom index and interstitial cystitis problem index, pelvic pain and urgency/frequency scores, risk factors for recurrence, and postoperative recurrence-free time. The median duration of follow-up was 16.0 months (interquartile range 11.75-21 months). Patients who underwent modified BoNT-A injections showed significant improvement in postoperative global response assessment, symptom questionnaires, and pain assessment compared with those who underwent conventional surgery. A statistically significant difference was observed between the 2 groups in terms of recurrence-free time (12.5 vs 18.0 months, P =.02). Subgroup analysis suggested that additional PUI of BoNT-A was more effective in patients with combined severe periurethral pain. No serious complications occurred in both groups, and all minor postoperative complications were temporary. Modified BoNT-A injection is an effective treatment for IC/BPS that significantly reduces pain and improves voiding symptoms. It is particularly effective in patients with combined periurethral pain. In such patients, PUI of BoNT-A should be added to the routine intravesical injection of BoNT-A. [ABSTRACT FROM AUTHOR]

To improve diagnosis of interstitial cystitis (IC)/bladder pain syndrome(IC) we hereby developed an improved IC risk classification using machine learning algorithms. A national crowdsourcing resulted in 1264 urine samples consisting of 536 IC (513 female, 21 male, 2 unspecified), and 728 age-matched controls (318 female, 402 male, 8 unspecified) with corresponding patient-reported outcome (PRO) pain and symptom scores. In addition, 296 urine samples were collected at three academic centers: 78 IC (71 female, 7 male) and 218 controls (148 female, 68 male, 2 unspecified). Urinary cytokine biomarker levels were determined using Luminex assay. A machine learning predictive classification model, termed the Interstitial Cystitis Personalized Inflammation Symptom (IC-PIS) Score, that utilizes PRO and cytokine levels, was generated and compared to a challenger model. The top-performing model using biomarker measurements and PROs (area under the curve [AUC] = 0.87) was a support vector classifier, which scored better at predicting IC than PROs alone (AUC = 0.83). While biomarkers alone (AUC = 0.58) did not exhibit strong predictive performance, their combination with PROs produced an improved predictive effect. IC-PIS represents a novel classification model designed to enhance the diagnostic accuracy of IC/bladder pain syndrome by integrating PROs and urine biomarkers. The innovative approach to sample collection logistics, coupled with one of the largest crowdsourced biomarker development studies utilizing ambient shipping methods across the US, underscores the robustness and scalability of our findings. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The primary aim was to examine the relationship between lower urinary tract symptoms (LUTS), toileting behaviors, and pelvic floor health knowledge in younger and older women. The secondary aim was to compare LUTS, toileting behaviors, and pelvic floor health knowledge in younger and older women. Methods: The study included 85 younger women and 81 older women. LUTS were evaluated using the International Consultation on Incontinence Questionnaire-Female LUTS (ICIQ-FLUTS), toileting behaviors using Toileting Behavior-Women's Elimination Behaviors (TB-WEB), and pelvic floor health knowledge using the Pelvic Floor Health Knowledge Quiz (PFHKQ). Results: In terms of LUTS, the most common symptoms in younger women are urgency (31.8%), bladder pain (28.2%), and frequency of incontinence episodes (35.3%), whereas in older women, the most common symptoms observed are urgency (64.2%), frequency of incontinence episodes (61.7%), intermittency (46.9%), urgency urinary incontinence (58%), and frequency of incontinence episodes (49.4%). Most unhealthy toileting behaviors correlated with LUTS in both groups (p < 0.05). Although a weak negative correlation was detected between ICIQ-FLUTS total score and PFHKQ function in younger women (p < 0.05), no correlation was found in older women (p < 0.05). Whereas premature voiding, straining during voiding, TB-WEB total score were higher in older women than in younger women (p < 0.05), delayed voiding, position preference for voiding, and PFHKQ function/dysfunction scores were higher in younger women than in older women (p < 0.05). Conclusions: Within the scope of preventive health services, it may be important to provide informative programs on healthy toileting behaviors and pelvic floor health to women of all ages in order to prevent LUTS. [ABSTRACT FROM AUTHOR]

Background: Laser therapy is a developing treatment for painful bladder syndrome (PBS), also known as interstitial cystitis (IC). Two main types of lasers are used for IC/PBS: Erbium:YAG (Er:YAG) lasers and low-level laser therapy (LLLT). More research is needed to determine the long-term effectiveness and safety of laser therapy for IC/PBS. Objective: This study aimed to determine the effect of low intensity laser therapy (LILT) on painful bladder syndrome. Subjects and methods: This study included fifty male patients with painful bladder syndrome or interstitial cystitis. They were split into two equal groups: Study group (A) and control group (B). Every patient in the two groups had the same standard physical treatment along with pelvic floor exercises to perform at home. Every patient also received the same prescription drugs and medical attention. For three months, Group (A) got low-intensity laser therapy in addition to conventional physical therapy and medical attention. For three months, the control group (B) only got standard medical care and physical therapy; each treatment session lasted for twenty minutes. The patient was in a comfortable supine posture when the 10-minute LILT application was placed suprapubically, and the patient was in a comfortable prone position when the other 10-minute application was placed beneath the lower back (T10-L1). Visual analogue scale (VAS) measurement and clomipramine medication consumption estimation (CMI) were used. Results: Results showed a highly significant reduction in VAS and CMI at the end of the treatment program in groups (A) only. Conclusion: So, LILT was effective in improving the interstitial cystitis/painful bladder syndrome as manifested by the highly significant reduction in VAS and CMI. [ABSTRACT FROM AUTHOR]

Oxidative stress resulting from reactive oxygen species (ROS) is often considered to be the leading cause of interstitial cystitis (IC), which is a chronic inflammatory disease. Antioxidants have been proven to have promising therapeutic effects on IC. In this study, we present an antioxidant intervention for IC by introducing curcumin-loaded cerium oxide nanoparticles (Cur-CONPs). Recognizing oxidative stress as the primary contributor to IC, our research builds on previous work utilizing cerium oxide nanoparticles (CONPs) for their outstanding antioxidant and anti-inflammatory properties. However, given the need to effectively relieve acute inflammation, we engineered Cur-CONPs to harness the short-term radical-scavenging antioxidant prowess of curcumin. Through in vitro studies, we demonstrate that the Cur-CONPs exhibit not only robust antioxidant capabilities but also superior anti-inflammatory properties over CONPs alone. Furthermore, in vivo studies validate the therapeutic effects of Cur-CONPs on IC. Mice with IC subjected to the Cur-CONP treatment exhibited improved micturition behaviors, relief from pelvic pain sensitivity, and reduced expression of inflammatory proteins (IL-6, IL-1β, TNF-α, Cox2). These findings suggest that the synergistic antioxidant properties of the Cur-CONPs that combine the sustained antioxidant properties of CONPs and acute anti-inflammatory capabilities of curcumin hold promise as a novel treatment strategy for IC. [ABSTRACT FROM AUTHOR]

IntroductionInterstitial 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.MethodsBladder 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.ResultsOur 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.DiscussionThe 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.

Introduction: Platelet-rich plasma (PRP) has become an increasingly popular therapeutic tool across various medical specialties since its introduction in 1958. Defined as a concentrated solution of platelets and growth factors derived from autologous blood, PRP supports tissue repair and regeneration processes. PRP’s composition includes high concentrations of platelets and growth factors that facilitate angiogenesis, connective tissue remodeling, and cellular repair, making PRP a promising treatment option for complex urological conditions and beyond. Purpose of the study: This review aims to summarize the applications and efficacy of PRP in treating specific urological conditions such as erectile dysfunction, Peyronie's disease, urethral stricture, hypospadias, interstitial cystitis and urinary incontinence. Materials and Methods: To provide a comprehensive summary of current knowledge on this topic, a literature review of English-language articles, with an emphasis on recent publications, was conducted. The review utilized the PubMed database and included 51 studies accessed prior to October 2024. Conclusions: PRP therapy appears to be a promising, safe, and minimally invasive treatment option for several urological conditions. Studies suggest that PRP may benefit erectile function, reduce symptoms in Peyronie's disease, and improve outcomes in conditions related to the urethra and bladder, with minimal reported adverse effects. However, the lack of standardized PRP preparation protocols and large placebo-controlled trials poses a challenge to fully establishing its efficacy. Further research is necessary to confirm PRP’s effectiveness, optimize preparation and administration methods, and develop guidelines for its clinical application in urology.

Purpose To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. Methods A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. Results The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. Conclusions HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.

The International Urogynecology Journal (IUJ) has seen significant success in 2024, with a focus on metrics beyond traditional citations to measure impact. The journal's top downloaded articles cover diverse topics such as postpartum diastasis recti rehabilitation, vibrators for pelvic health, and conservative treatments for urinary incontinence. The IUJ emphasizes open-access publishing and aims to enhance accessibility to high-quality research globally, reflecting its commitment to advancing urogynecology through innovative and impactful research. [Extracted from the article]

The document titled "Posttest Questions" from FP Essentials provides a series of questions related to various gynecological and urological conditions, including dyspareunia, vulvar pain, urinary incontinence, and interstitial cystitis/bladder pain syndrome. The questions cover topics such as diagnosis, treatment options, and screening recommendations for these conditions. The questions are designed to test knowledge and understanding of these issues in clinical practice. Readers can access the posttest questions online to earn CME credits. [Extracted from the article]

The editorial discusses the challenges of prolonged wait times and increasing complexity in gynaecological care, particularly in public hospitals in Victoria, Australia. Factors contributing to this issue include demographic changes, operational inefficiencies, and evolving patient expectations. The COVID-19 pandemic exacerbated the situation by shifting outpatient care to telehealth consultations, leading to delays in patient management. Proposed solutions include enhanced GP education, utilisation of specialist hubs, shared care models, and lifestyle interventions to address systemic issues and improve patient care. [Extracted from the article]

The article "Dysuria in the Collegiate Athlete" discusses a case study of a 21-year-old female soccer athlete presenting with symptoms of dysuria. The initial diagnosis of a urinary tract infection (UTI) was later revised to nephrolithiasis after further evaluation. The article emphasizes the importance of considering a broad range of differential diagnoses, including interstitial cystitis and pelvic myofascial pain, in cases of recurrent urinary symptoms. It also highlights the need for a thorough clinical evaluation and appropriate management tailored to the individual athlete's needs. [Extracted from the article]

Radiation therapy is often utilised for the treatment of pelvic malignancies. Radiation-induced haemorrhagic cystitis can occur in such patients and may sometimes lead to uncontrolled haematuria. Various treatment modalities for managing this condition include urinary bladder irrigation, cystoscopy-guided procedures, hyperbaric oxygen therapy, fulguration, and other surgical techniques. Transarterial super-selective vesical artery embolisation has emerged as a modern management technique for patients with refractory radiation-induced haemorrhagic cystitis. Hereby, the authors present a case report of a 62-year-old elderly female patient diagnosed with radiation-induced haemorrhagic cystitis, which was refractory to continuous urinary bladder irrigation and medical management. She was successfully treated with super-selective vesical artery embolisation, resulting in complete resolution of haematuria, even on follow-up. This minimally invasive and effective modality can be utilised as a first-line therapy as well as in cases where other treatment options have failed. [ABSTRACT FROM AUTHOR]

Background: This multicentric prospective study was carried out at Fondazione Policlinico Universitario Campus Bio Medico and Ospedale di Stato of St. Marino Republic. Between 1 January 2019, and 31 December 2022, all pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis at both centers were included in the study. The main aim of the study was to assess the effectiveness of vaginal CO2 laser treatment, alone or combined with intravesical hyaluronic acid instillations, in managing cystitis symptoms, such as dysuria, pollakiuria, and urgency, across the entire patient cohort. The secondary objective was to investigate the reduction in number of annual cystitis episodes post-treatment. Methods: Each woman underwent three to four sessions of micro-ablative CO2 vaginal laser treatment. A follow-up examination was conducted 12 months after the final laser session (up to December 2023), during which a post-treatment VAS assessment evaluated dysuria, daily pollakiuria, and urgency. The enrolled patients recorded the number of cystitis episodes experienced during the 12-month pre- and post-treatment period. Results: Results indicated the laser's efficacy in reducing the total number of cystitis episodes per year and an improvement in symptoms up to one year post-treatment. Greater efficacy of the CO2 laser treatment, particularly when combined with intravesical hyaluronic acid instillation, was observed in both pre- and post- menopausal women. Conclusions: Fractional CO2 laser therapy represents a safe and efficacious, non-hormonal approach for pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis. [ABSTRACT FROM AUTHOR]

The efficacy of hyaluronic acid instillations as therapy for patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) has been demonstrated in some clinical studies, with response rates up to 70%. The aim of the study is to investigate the change in symptoms and quality of life in female patients with IC/BPS after intravesical instillations of hyaluronic acid used as first-line treatment. A retrospective single-center cohort study was conducted. Female patients, whose symptoms were compatible with the diagnosis of IC/BPS as defined by the International Continence Society, were treated with a variable number of intravesical instillations of a hyaluronic acid-based drug. Three validated questionnaires were administered by telephone to all patients, before the beginning of the treatment and 6 months after the last administration of the drug. A total of 50 patients with symptoms compatible with the diagnosis of IC/BPS were included in the study. The median number of instillations performed is 4. For all questionnaires, the median value was significantly reduced following treatment with intravesical instillations (p = 0.000). The present study has shown that intravesical hyaluronic acid treatment results in both statistically and clinically significant symptomatic improvement, thereby improving the quality of life of patients with IC/BPS. [ABSTRACT FROM AUTHOR]

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disabling bladder condition. ESSIC, the IC/BPS society defines two types of IC/BPS: with Hunner's lesion (HL) and without. Pathogenesis is stated as unknown, with no cure possible. Scheffler in 2021 reported cystoscopically validated cure of HL IC/BPS by repair of uterosacral ligaments (USLs) and in 2022, Goeschen reported non-HL IC/BPS cure in 198 women following USL repair. Both Scheffler and Goeschen hypothesized IC/BPS may be a phenotype of the Integral Theory's Posterior Fornix Syndrome "PFS" (chronic pelvic pain, OAB, and emptying dysfunctions) and therefore potentially curable. Summary: The hypothesis explores whether visceral plexuses (VPs), due to weakened USLs support, serve as a primary source of pelvic pain impulses, leading to development of an inflammatory condition – for example, IC/BPS, a chronic inflammatory condition, which shares similarities with vulvodynia and complex regional pain syndrome (CRPS). According to our hypothesis, such conditions involve axon reflexes. Stimuli such as gravity applied to unsupported nerve branches within the visceral pelvic plexus, trigger centrally propagating impulses, which then progress antidromally to influence innervated tissues through cytokine release and nociceptor stimulation, perpetuating inflammatory processes at the end organs, and pain perception. Key Messages: The hypothesis raises the question, "are IC/BPS, vulvodynia, other pain sites, even nonbacterial "chronic prostatitis" in the male, different phenotypes of the chronic pelvic pain syndrome which includes PFS. If so, the hypothesis opens several new research directions and would predict inflammatory findings in tender end organ pain sites. [ABSTRACT FROM AUTHOR]

Objective: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by many urologic symptoms, including urgency, frequency, and pelvic pain. While 3 of the current authors and other colleagues described the value of micronized amniotic membrane (AM) injection previously to improve lower urinary-tract symptoms in patients with IC/BPS, this study specifically evaluated intradetrusor injections of micronized AM for patients with IC/BPS and concurrent female sexual dysfunction (FSD). Materials and Methods: Eleven consecutive patients with symptoms recalcitrant to multiple other therapies received intradetrusor injections of 100 mg of micronized AM (Clarix Flo® BioTissue, Miami, FL, USA) diluted in 10 mL of 0.9% preservative-free sodium chloride. Results: All patients had severe IC/BPS symptoms at baseline, with an average Interstitial Cystitis Symptoms Index (ICSI) score of 20.9 ± 0.3 and an average Problem Index (ICPI) score of 16 ± 0.0 that decreased to 5.8 ± 1.4 and 4.4 ± 1.4, respectively, at 12 weeks after treatment. Additionally, sexual function, measured by the Female Sexual Function Index (FSFI), improved from 21.2 ± 6.5 to 27.8 ± 6.8 at 12 weeks. This coincided with a reduction of pain associated with intercourse from 8.4 ± 0.9 to 6.3 ± 1.2 at 12 weeks. Conclusions: Amniotic bladder therapy could be a valuable treatment for IC/BPS with FSD, based on these encouraging results at 12 weeks after treatment. (J GYNECOL SURG 20XX:000) [ABSTRACT FROM AUTHOR]

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition with critical symptoms of urinary urgency and frequency, persistent bladderrelated pain, and reduced quality of life. Poor-quality sleep can lead to significant disturbances in daily life and increased pain in IC/BPS patients. Resilience, depressive symptoms, and pain catastrophizing have univariate associations with sleep and pain in IC/BPS, suggesting they may be mechanisms in this sleep and pain relationship. METHODS: This online study recruited patients self-reporting a diagnosis of IC/BPS through support groups, social media posts (Facebook, Reddit, and Instagram), and urology clinic advertisements. Participants completed questionnaires on demographics, urologic symptoms, pain, pain catastrophizing, depressive symptoms, and resilience. Only those participants who met the RAND Interstitial Cystitis Epidemiology (RICE) criteria for IC/BPS diagnosis were included. A multiple mediation model was first examined, followed by a serial mediation model. RESULTS: Seventy-four participants (Mage= 47.0, standard deviation [SD] 16.7, range 18-83 years) met inclusion criteria. A multiple mediation model showed greater sleep disturbance was associated with greater pain severity through depressive symptoms and pain catastrophizing, but not resilience (b=0.79, bootSE=0.26, bootCI [0.33, 1.35]). A serial mediation showed that the sleep-to-pain relationship had a significant indirect effect through pain catastrophizing and depressive symptoms (b=0.78, bootSE=0.26, bootCI [0.35, 1.32]). CONCLUSIONS: Findings suggest depressive symptoms and pain catastrophizing may be important psychosocial mechanisms in the sleep-to-pain relationship. These results help guide future sleep and pain research in IC/BPS and aid in developing and refining treatments. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Bladder pain syndrome (BPS) is a debilitating condition characterised by exaggerated bladder sensations and altered bladder function. It is still unknown whether the condition is a peripheral sensory problem or due to abnormal central sensory processing as seen in central sensitisation. This systematic review, which followed a published and Prospective Register of Systematic Reviews-registered protocol (CRD42021229962), is aimed at establishing the scope of central sensitisation in patients with BPS to aid optimal management and treatment. Methods: Four databases were searched, and appraisal of the identified studies was conducted by two independent reviewers based on eligibility criteria: patients with BPS being investigated for central sensitisation with or without comparison of controls, English-language articles, full text and publication in a peer-reviewed journal. The Methodological Index for non-Randomised Studies was used to determine study quality. We identified 763 papers in total, with 15 studies included in the final analysis. All studies were observational and had a low risk of bias. Measures included in the evaluation of CS were questionnaires, urodynamics, and quantitative sensory testing methods. Results: There was evidence of central sensitisation in patients with BPS in all papers evaluated (15 out of 15). In addition, more significant central sensitisation correlated with severe disease presentation (3 out of 3 papers) and concomitant chronic pain conditions (5 out of 5 papers). Conclusions: Central sensitisation plays an integral role in BPS patient pathology. Many secondary measures are used to evaluate this condition. Stratification of patients based on their pathology (peripheral, central or a combination of the two) will aid in implementing an individualised management strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To critically analyse the relationship of bladder pain syndrome (BPS/IC), as defined, to the posterior fornix syndrome, "PFS" predictably co-occurring bladder urgency, frequency, nocturia, chronic pelvic pain, emptying symptoms/retention, caused by uterosacral ligament (USL) laxity and cured by USL repair. The starting and end points of this paper are the questions, "Are there arguments that BPS/IC can, in some cases, be linked to PFS?" And if so, "To what extent?" We used the criteria required by Ueda for proper diagnosis: "understanding symptoms, detecting abnormal findings and verifying them as a cause of the symptoms." Literature, diagnostic and surgical, indicate that chronic pelvic pain "of unknown origin" can be caused by unsupported visceral pelvic plexuses because of weak USLs; these cause fire of afferent impulses, which the brain mistakenly interprets as coming from the end-organ itself (i.e., genitourinary pain, lower urinary tract symptoms). The same lax USLs can also weaken the pelvic muscles which contract to stretch the vagina to support the urothelial stretch receptors from below: these may prematurely fire off afferent impulses to activate micturition at lower bladder volumes, interpreted as urgency. A speculum placed in the vagina can relieve pain and urgency by mechanically supporting the vaginal wall and USLs, thus predicting an eventual cure by USL repair. There is need to evaluate what percentage of women with known BPS/IC also pass the criteria for PFS. Identifying a significant percentage of BPS/IC women with the causative relation between PFS pathogenesis and BPS/ IC may open a new way of diagnosing and treating BPS/IC in some women. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. Methods: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. Results: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. Conclusions: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone. [ABSTRACT FROM AUTHOR]

Purpose of Review: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disease that causes bladder symptoms such as pelvic pain and frequent urination and is often an intractable disease affecting a patient's quality of life. The etiology of IC/BPS remains elusive, and treatment strategies are still not fully established. To better understand the underlying pathophysiology, many studies have strived to recreate an animal model of IC/BPS to help further expand the treatment options of this difficult disease. Recent Findings: Basic animal studies of IC/BPS have often been conducted by provoking inflammation in the bladder, which is useful at least in part due to the similarity of the pathophysiology to profound inflammatory responses in IC/BPS, especially in the Hunner lesion subtype. Also, other animal models such as bladder stimulation models, pelvic organ cross-sensitization models, autoimmune models, and psychological stress models have been explored and shown various new outsights. However, the predicted underlying etiology of IC/BPS is complex often with a combination of inflammation, ischemia, and neurogenic changes, which makes it challenging for researchers to translate the results in animal models to clinical applications. Summary: Each animal model that is containing a piece of the underlying etiology of IC/BPS cannot be obtained alone, but by forming a picture by using each piece adequately will enable us to expand the horizon of the unexplored pathophysiology, which will lead us to identify novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose of Review: The article aims to outline the pathogenesis, etiology, prevalence, and evaluation of chronic pelvic pain as it pertains to patients with two of the common causes: IBS and UCPPS. Recent Findings: Because both diseases are diagnoses of exclusion, it is important to rule out other similar diagnoses. Biological markers are a new research frontier for identifying UCPP. Summary: A careful and multimodal approach is then taken to address the patient's goals and seek to optimize the QOL. [ABSTRACT FROM AUTHOR]

Zinner Syndrome (ZS) and Herlyn-Werner-Wunderlich Syndrome (HWWS) are congenital genitourinary anomalies accompanied by ipsilateral renal agenesis. These syndromes, which can cause symptoms such as infertility, pelvic pain, and bladder irritation, can be diagnosed by digital rectal examination, transrectal and abdominal ultrasonography (US), Computer Tomography (CT) and more ideally Magnetic resonance imaging (MRI). Similar physiopathological processes are observed in both syndromes and urogenital malformations accompany renal agenesis. We aimed to discuss the three cases of ZS in men and two HWWS cases in women, which are rarely observed in the literature. [ABSTRACT FROM AUTHOR]

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner‐type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single‐cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor‐like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3–NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self‐repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Introduction: Lower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract. Methods: A panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings. Results: Childhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross‐talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age‐related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities. Conclusion: Understanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross‐talk, and uncover molecular signatures for personalized management. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) presents as a chronic pain condition with variable combinations of symptoms depending on the species and individual patient. It is diagnosed by the presence of lower urinary tract signs and symptoms in combination with a variety of comorbid health problems, a history of life adversities, and the absence of other conditions that could cause the lower urinary tract signs. IC occurs naturally in humans and cats as a dimensional condition, with patients presenting with mild, moderate, and severe symptoms. Most patients appear to recover without specific treatment. A number of rodent models of IC have been used to study its causes and treatments. Unfortunately, current therapies generally fail to ameliorate IC symptoms long-term. The recent classification of IC as a chronic primary pain disorder calls for a rethinking of current clinical and research approaches to it. Beginning when a patient encounters a clinician, precipitating, perpetuating, and palliating risk factors can be addressed until a cause or reliably effective therapy is identified, and identifying predisposing and preventive factors can inform epidemiological studies and health promotion interventions. Predisposing, precipitating, and perpetuating risk factors, including environmental, psychological, and biological, increase the activity of the central threat response system (CTRS), which plays a clinically important role in IC symptoms. Studies in cats and rodent models have revealed that environmental enrichment (EE), in the absence of bladder-directed therapies, leads to amelioration of IC symptoms, implying a central role for the CTRS in symptom precipitation and perpetuation. Conceptually moving the source of IC pain to the brain as a motivational state rather than one resulting from peripheral nociceptive input offers both clinicians and researchers novel opportunities to improve care for patients with IC and for researchers to use more ecologically valid rodent models. It may even be that IC results from an excess of risk to protective factors, making this imbalance a targetable cause rather than a consequence of IC. [ABSTRACT FROM AUTHOR]

Background: Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. Methods: Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. Results: Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor. Conclusions: In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA. [ABSTRACT FROM AUTHOR]

Purpose: The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing and analyzing the data linking microRNAs (miRNAs) expression in the pathophysiology of benign urological conditions, including overactive bladder (OAB), bladder outlet obstruction (BOO), bladder pain syndrome/interstitial cystitis (BPS/IC), and Lower urinary tract dysfunction (LUTD) is the objective of the current systematic review. Materials and Methods: Evidence including all case-control, cohort, and cross-sectional studies that measure participants' MicroRNA as a biomarker for benign urological diseases has been gathered On January 2024, through searching MEDLINE via PubMed, Scopus, Web of Science, Embase, and ProQuest databases. Studies considered eligible that present information on the reference Gene, profile type, and serum levels of microRNA from patients diagnosed with benign urological disease including benign prostate hyperplasia (BPH) or benign prostate enlargement (BPE), overactive bladder (OAB), and bladder outlet obstruction (BOO). These studies appraised by the quality assessment checklist of Joanna Briggs Institute (JBI). Results: A total of 4,587 records related to miRNAs in urological diseases were retrieved. Of these, we identified 28 records for our systematic study. The most frequently associated miRNA was 92a-3p identified which was found upregulated in OAB diagnosis. In BOO, miR-146a-5p was identified to be upregulated. miR-146a-5p was upregulated in BO, and for other benign conditions, different miRNAs were reported. 491-5p miRNAs were found deregulated in OAB-related studies. We expected other miRNAs to have the same trend in the OAB studies. InSUI miR-93 was the most frequent downregulated miRNA. The other reported miRNAs had similar frequencies. Conclusion: When it comes to the early detection and treatment of benign urological conditions, 92a-3p, miR-21, miR-199a-5p, and miR-146a-5p, and 491-5p have the potential to be employed as both a biomarker and a therapeutic target. The creation of pre-RNA or anti-RNA molecules within carrier vehicles that may be safely administered to patients should be made possible by technological advancements. [ABSTRACT FROM AUTHOR]

Urinary dysfunction encompasses a wide range of syndromes and symptoms and is highly prevalent among the adult population. Urinary issues have been associated with psychosocial sequelae. The interplay between psychosocial comorbidity and symptoms impacts perceived severity and treatment success. While the correlation has been described in the literature, much remains unknown. This article describes the psychosocial impact on conditions such as overactive bladder (OAB), neurogenic lower urinary tract dysfunction (LUTD), recurrent urinary tract infection (UTI), and interstitial cystitis/bladder pain syndrome (IC/BPS). This article also highlights potential interventions for patients afflicted with both urinary disorders and psychosocial comorbidity to improve overall treatment success. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). Methods: We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges' g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. Results: A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. Conclusion: This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. Trial registration: PROSPERO CRD42022384024 [ABSTRACT FROM AUTHOR]

Bladder pain is a prominent symptom in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We studied spinal mechanisms of bladder pain in mice using a model where repeated activation of intravesical Protease Activated Receptor-4 (PAR4) results in persistent bladder hyperalgesia (BHA) with little or no bladder inflammation. Persistent BHA is mediated by spinal macrophage migration inhibitory factor (MIF), and is associated with changes in lumbosacral proteomics. We investigated the contribution of individual spinal MIF receptors to persistent bladder pain as well as the spinal proteomics changes associated with relief of persistent BHA by spinal MIF antagonism. Female mice with persistent BHA received either intrathecal (i.t.) MIF monoclonal antibodies (mAb) or mouse IgG1 (isotype control antibody). MIF antagonism temporarily reversed persistent BHA (peak effect: 2 h), while control IgG1 had no effect. Moreover, i.t. antagonism of the MIF receptors CD74 and C-X-C chemokine receptor type 4 (CXCR4) partially reversed persistent BHA. For proteomics experiments, four separate groups of mice received either repeated intravesical scrambled peptide and sham i.t. injection (control, no pain group) or repeated intravesical PAR4 and: sham i.t.; isotype IgG1 i.t. (15 μg); or MIF mAb (15 μg). L6-S1 spinal segments were excised 2 h post-injection and examined for proteomics changes using LC-MS/MS. Unbiased proteomics analysis identified and relatively quantified 6739 proteins. We selected proteins that showed significant changes compared to control (no pain group) after intravesical PAR4 (sham or IgG i.t. treatment) and showed no significant change after i.t. MIF antagonism. Six proteins decreased during persistent BHA (V-set transmembrane domain-containing protein 2-like confirmed by immunohistochemistry), while two proteins increased. Spinal MIF antagonism reversed protein changes. Therefore, spinal MIF and MIF receptors mediate persistent BHA and changes in specific spinal proteins. These novel MIF-modulated spinal proteins represent possible new targets to disrupt spinal mechanisms that mediate persistent bladder pain. [ABSTRACT FROM AUTHOR]

•we report the case of a 36-year-old female patient who presented to our hospital with a diagnosis of cystitis glandularis manifesting as a vesicovaginal fistula. She underwent cystoscopic biopsy at a local hospital, but anti-inflammatory treatment was ineffective, and the patient was experiencing low urination frequency and urgency, as well as pain. The patient underwent laparoscopic repair of a cystoscopy-confirmed vesicovaginal fistula. After surgery, the patient experienced a paroxysm of Crohn's disease with multiple small bowel fistulas and erosion of the external iliac vessels that ruptured to form an external iliac vessel small bowel fistula. The fistula was confirmed by surgical exploration, and the patient eventually died. [ABSTRACT FROM AUTHOR]

Objectives: Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. Materials and methods: 45 women with VO-CPP were treated with venous stenting and/or embolization. Four surveys assessed symptoms pre- and post-treatment: IPPS (chronic pelvic pain), PUF (interstitial cystitis), OHQ (dysautonomia), and modified ROME III (IBS). Prevalence of joint hypermobility was investigated. Results: Ages were 18–65. Pretreatment, 64% and 49% of women were in the severe range for PUF and OHQ, respectively. 40% and 56% met criteria for IBS and Ehlers-Danlos syndrome/Hypermobility Spectrum Disorder (EDS/HSD), respectively. 17eceived an iliac stent, 5 pelvic embolization, and 23 both. Post-treatment, average scores improved: IPPS (by 55%), PUF (34%), and OHQ (49%). Rome III improved only slightly. Conclusion: Pelvic pain, interstitial cystitis, and dysautonomia were frequently found with VO-CPP and improved after venous treatment. EDS/HSD and IBS were common in these women. [ABSTRACT FROM AUTHOR]

A multiple sclerosis (MS) prodrome has recently been described and is characterised by increased rates of healthcare utilisation and an excess frequency of fatigue, bladder problems, sensory symptoms and pain, in the years leading up to clinical onset of disease. This important observation may have several potential applications including in the identification of risk factors for disease, the potential to delay or prevent disease onset and early opportunities to alter disease course. It may also offer possibilities for the use of risk stratification algorithms and effective population screening. If standardised, clearly defined and disease specific, an MS prodrome is also likely to have a profound influence on research and clinical trials directed at the earliest stages of disease. In order to achieve these goals, it is essential to consider experience already gleaned from other disorders. More specifically, in some chronic neurological disorders the understanding of disease pro-drome is now well advanced and has been successfully applied. However, understanding of the MS prodrome remains at an early stage with key questions including the length of the prodrome, symptom specificity and potential benefits of early intervention as yet unanswered. In this review we will explore the evidence available to date and suggest future research strategies to address unanswered questions. In addition, whilst current understanding of the MS prodrome is not yet sufficient to justify changes in public health policy or MS management, we will consider the practical utility and future application of the MS prodrome in a wider health care setting. [ABSTRACT FROM AUTHOR]

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson's trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications. [ABSTRACT FROM AUTHOR]

Purpose: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). Materials and Methods: A previously validated smart phone app (M‐app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M‐app notifications were sent 4‐times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined. Results: A total of 204 participants enrolled in the M‐app study (64% female). M‐app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability. Conclusions: PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease of unknown etiology, characterized by bladder pain and frequency urgency symptoms. Based on the cystoscopic findings after hydrodistention under anesthesia, the phenotype of IC/BPS includes no glamerulation, characteristic glomerulation, and with Hunner's lesion. IC is specifically defined if there are characteristic Hunner's lesion appeared in cystoscopy or after hydrodistention. If there are glomerulations without Hunner's lesion, BPS should be considered. The definition of Hunner's lesion and glomerulations differs based on different definition and observations. Currently, there has been no clear description and grading of the glomerulations and Hunner's lesion. Because the classification of IC/BPS has an impact on the treatment strategy and associated with therapeutic outcome, it is unmet to have a clear definition and consensus on the characteristic cystoscopic findings of IC/BPS. This article reviews the literature and presents the figures of Hunner's lesions and description of different mucosal lesions after cystoscopic hydrodistention.

Hyperbaric oxygen (HBO2) therapy is a UHMS-approved treatment for radiation cystitis and has been used for other causes of cystitis such as cyclophosphamide-induced hemorrhagic cystitis and interstitial cystitis, among others. Immunotherapy with Bacillus Calmette-Guérin (BCG) is the most effective treatment of non-muscle invasive bladder cancer. BCG acts as a non-specific stimulant of the reticuloendothelial system, causing a local inflammatory response. BCG attaches to bladder tumor cells as well as urothelial cells which then stimulates an immune response involving a multitude of cytokines and local migration of polymorphonuclear cells that leads to death of the cancer cells. The typical protocol of a single six-week course has been shown to provide long-term protection from tumor recurrence and to reduce disease progression. Irritative bladder side effects are common, but serious side effects are uncommon. Two cases of severe BCG-cystitis treated with HBO2 are presented. Two male patients with bladder cancer were treated with intravesicular BCG. Each developed complications of pain, spasms, urinary frequency and nocturia; one developed gross hematuria. Cystoscopy showed friable mucosa. They failed standard medical therapy and were referred for HBO2. They were treated in a multiplace chamber at 2.2-2.4 ATA. One patient received 60 and the other 40 treatments. Both experienced substantial reduction in their symptoms. BCG cystitis may be considered for HBO2 if other standard therapy has failed.