Pentosan polysulfate maculopathy: clinical considerations, pathobiology, and causality.

In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA). Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.

To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice. Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells. PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA. PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.

To report a case of angiographically silent cystoid macular edema (CME) secondary to pentosan polysulfate sodium (PPS) maculopathy responsive to intravitreal steroids. Observational case report. A 52-year-old female patient with a history of 4 years of PPS use for interstitial cystitis presented with PPS maculopathy that developed CME 2.5 years after drug cessation and had associated progression of pigmentary and atrophic changes. Her CME was nonresponsive to topical ketorolac and dorzolamide, but was responsive to intravitreal triamcinolone acetonide and subsequently intravitreal dexamethasone implant (Ozurdex) with reduction in central subfield thickness and improvement in visual acuity. Cystoid macular edema secondary to PPS maculopathy may be angiographically silent yet responsive to intravitreal steroids alone without the use of vascular endothelial growth factor agents. There is potential for both anatomic and functional improvements in such cases demonstrating the value of such treatment. Cystoid macular edema may be a delayed finding that can develop despite drug cessation. Steroid monotherapy should be further evaluated as possible first-line management for PPS maculopathy-associated CME.

Background: Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain and lower urinary tract symptoms. Pentosan polysulfate sodium (PPS) is the only oral therapy licensed in the United Kingdom (UK) for BPS; however, evidence on its effectiveness is inconsistent, with limited data for off-label use in ketamine- or radiation-induced cystitis. Objective: This study evaluates real-world outcomes of PPS in patients with BPS and other chronic bladder pain at a UK tertiary center. Methods: A retrospective review included 42 patients prescribed PPS between 2020 and 2024 for BPS (n = 29), ketamine-induced cystitis (n = 9), or radiation/chemotherapy-induced cystitis (n = 4), excluding Bacillus Calmette–Guérin cystitis. Demographics, comorbidities, prior treatments, symptom severity, and treatment response were recorded. Changes in quality of life (QoL) and Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index (ICSI/ICPI) scores were analyzed using the Wilcoxon signed-rank test and one-way analysis of variance. Results: The mean age was 49.7 years, and 81% were female, with a median follow-up of 15.3 months. All patients were severely symptomatic at baseline. Among those with follow-up data, 42.5% were asymptomatic, 25% mildly symptomatic, and 32.5% remained severely symptomatic. QoL improved significantly (Wilcoxon Z = −4.71, p<0.001). Greatest reductions in ICSI and ICPI scores were observed in BPS patients, with modest improvements in off-label groups. Side effects occurred in 14.2% of patients. PPS was associated with significant symptom improvement and acceptable tolerability in a treatment-refractory cohort, particularly in BPS. Conclusion: Modest benefits in ketamine- and radiation-induced cystitis suggest potential off-label utility, warranting further investigation. These findings support PPS use in selected cases, while accounting for placebo effects and disease heterogeneity.

Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization. Self-evaluation scales can provide more objective results on pre- and post-treatment satisfaction. The aim of this study was to investigate the effect of pentosan polysulfate treatment on symptoms in IC-BPS patients. This study included 37 adult male and female patients with IC-BPS who reported pain, urinary urgency, polyurea, and nocturia without urinary tract infection for a minimum of six months prior to the study and were taking 300 mg/day oral pentosan polysulfate. Pre- and post-treatment symptoms, Interstitial Cystitis Symptom Index (ICSI) Scores, quality of life (QoL) scores (1-4), and satisfaction conditions were examined. Following the application of inclusion and exclusion criteria, mean age of 37 suitable patients was 46.0±11.9 years and 27% (10 individuals) of the patients were male. Pre-treatment, ICSI scores, and measures of satisfaction degree and QoL increased significantly after the treatment (p<0.001). Adverse reaction was detected in two patients (5.4%) among the patients treated with pentosan polysulfate. Oral pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome treatment could achieve recovery in symptoms, increase Interstitial Cystitis Symptom Index score and improve quality of life and patient satisfaction.

Traitements spécifiques du syndrome douloureux vésical

INTERSTITIAL CYSTITIS, CHRONIC NONBACTERIAL PROSTATITIS AND CHRONIC PELVIC PAIN SYNDROME IN MEN: A COMMON AND FREQUENTLY IDENTICAL CLINICAL ENTITY

Objectives:Hysterectomies may be performed unnecessarily in women with chronic pelvic pain if the diagnosis of interstitial cystitis is not considered. The objectives of this study were to investigate the prevalence of interstitial cystitis in patients with posthysterectomy chronic pelvic pain and to evaluate the efficacy of various therapies for interstitial cystitis.Methods:A study was performed of 111 patients with chronic pelvic pain whose pain persisted after hysterectomy. Patients were screened with the Pelvic Pain and Urgency/Frequency symptom scale, and underwent Potassium Sensitivity Testing. Patients were treated with dietary changes alone or in combination with cystoscopic hydrodistention or oral pentosan polysulfate, or both of these, for 3 to 6 months.Results:Of the 111 patients enrolled, 79% (n=88) were diagnosed with bladder dysfunction consistent with interstitial cystitis. For patients treated with dietary modification alone (n=33), the mean score on the Pelvic Pain and Urgency/Frequency questionnaire improved 15.4%, from 13.18 at baseline to 11.15 at follow-up. For patients treated with pentosan polysulfate or cystoscopic hydrodistention, or both, plus diet changes (n=78), Pelvic Pain and Urgency/Frequency scores improved 34.2%, from 15.01 to 9.87.Conclusion:In this study, nonsurgical treatment for interstitial cystitis resulted in a marked improvement in symptoms that had not improved with surgery. Without determining the origin of bladder pain, gynecologists should not proceed to hysterectomy in patients with chronic pelvic pain.

Age-Related Macular Degeneration Masquerade: A Review of Pentosan Polysulfate Maculopathy and Implications for Clinical Practice.

Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome.

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

Chronic musculoskeletal pain often co-occurs with Parkinson's disease (PD); however, whether individuals with chronic pain have a higher risk of developing PD is unclear. To investigate the associations between chronic pain and incident risk of three neurodegenerative parkinsonism categories including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). This study included 355,890 participants (mean [standard deviation] age, 56.51 [8.07] years, 48.40% male) who did not have parkinsonism at baseline from a population-based cohort. Musculoskeletal pain in the hip, neck/shoulder, back, knee, or "all over the body" was assessed. Chronic pain was defined if pain lasted ≥3 months. Participants were categorized into four groups: no chronic pain, having one or two, three or four sites, and pain "all over the body." The diagnosis of PD, MSA, and PSP used self-reports, hospital records, and death registries. Multivariable-adjusted Cox regression was performed for the analyses. Over a median follow-up of 13.0 years, 2044 participants developed PD, 77 participants developed MSA, and 126 participants developed PSP. In multivariable analyses, there was a dose-response relationship between number of chronic pain sites and incident risk of PD (hazard ratio, 1.15; 95% confidence interval, 1.07-1.23). Participants with one or two pain sites and three or four pain sites had an 11% and 49% increased risk of developing PD, respectively. There were no associations between chronic pain and MSA or PSP. Chronic musculoskeletal pain was independently associated with PD, suggesting that chronic pain could be used to identify individuals at risk of developing PD. © 2024 International Parkinson and Movement Disorder Society.

BackgroundChronic pain is highly prevalent in the general population and has been considered a disease entity in itself. Recent studies including our own have shown that chronic pain in multiple...

Introduction: Chronic neuropathic pain is as a severe detriment to overall quality of life for millions of Americans. Current pharmacological treatment options for chronic neuropathic pain are generally limited in efficacy and may pose serious adverse effects such as risk of abuse, nausea, dizziness, and cardiovascular events. Therefore, many individuals have resorted to methods of pharmacological self-treatment. This narrative review summarizes the existing literature on the utilization of two novel approaches for the treatment of chronic pain, cannabinoid constituents of Cannabis sativa and alkaloid constituents of Mitragyna speciosa (kratom), and speculates on the potential therapeutic benefits of co-administration of these two classes of compounds. Methods: We conducted a narrative review summarizing the primary motivations for use of both kratom and cannabis products based on epidemiological data and summarize the pre-clinical evidence supporting the application of both kratom alkaloids and cannabinoids for the treatment of chronic pain. Data collection was performed using the PubMed electronic database. The following word combinations were used: kratom and cannabis, kratom and pain, cannabis and pain, kratom and chronic pain, and cannabis and chronic pain. Results: Epidemiological evidence reports that the self-treatment of pain is a primary motivator for use of both kratom and cannabinoid products among adult Americans. Further evidence shows that use of cannabinoid products may precede kratom use, and that a subset of individuals concurrently uses both kratom and cannabinoid products. Despite its growing popularity as a form of self-treatment of pain, there remains an immense gap in knowledge of the therapeutic efficacy of kratom alkaloids for chronic pain in comparison to that of cannabis-based products, with only three pre-clinical studies having been conducted to date. Conclusion: There is sufficient epidemiological evidence to suggest that both kratom and cannabis products are used to self-treat pain, and that some individuals actively use both drugs, which may produce potential additive or synergistic therapeutic benefits that have not yet been characterized. Given the lack of pre-clinical investigation into the potential therapeutic benefits of kratom alkaloids against forms of chronic pain, further research is warranted to better understand its application as a treatment alternative.

Preoperative Opioid Use Is Associated With Persistent Use, Readmission and Postoperative Complications After Arthroscopic Knee Surgery