Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis.

OBJECTIVES: The objective of this study was to evaluate our experience using cyclosporine A (CyA) in the treatment of Hunner lesion interstitial cystitis (HLIC). METHODS: Retrospective chart review was performed on patients with HLIC treated with CyA from August 2012 to September 2019. Demographic and clinical variables, number of interstitial cystitis therapies, frequency, nocturia, and bladder pain visual analog scores before and after CyA treatment were collected, as well as the Global Response Assessment (GRA) and the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index. CyA responders were defined as those with moderately or markedly improved GRA scores. RESULTS: A total of 51 patients with HLIC treated with CyA were identified. Mean follow-up was 3 years (0.36-6.8 years). Seventy-six percent (28 of 37) were female; mean age was 68 years (51-84 years). Before CyA treatment, an average of 8 previous therapies were tried and patients reported an average of 8 of 10 bladder pain. Daytime frequency was 11-20 times per day, and nocturia was 7 times per night. Per the GRA, 84% (31 of 37) were considered CyA responders. Posttherapy Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were lower in responders compared with nonresponders (8.9 ± 5.7 vs 21.3 ± 7.0, P = 0.001). Bladder pain, number of hydrodistentions/fulgurations, nocturia, and daytime frequency improved significantly after CyA treatment. CONCLUSIONS: The cyclosporine A response rate was 84%, with most of these patients reporting marked improvement. Bladder pain, daytime frequency, and nocturia were significantly improved after CyA treatment, and the number of interventions after CyA treatment decreased. Cyclosporine A should be considered earlier than fifth-line therapy in HLIC.

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder.

We report on the first regulatory approved clinical trial of a prospective open-label physician-initiated study assessing the safety and efficacy of intradetrusor injected Autologous Muscle Derived Cells (AMDC) treatment for underactive bladder (UAB). 20 non-neurogenic UAB patients were treated. Approximately 50-250 mg of quadriceps femoris muscle was collected using a spirotome 8-gauge needle. The muscle biopsy samples were sent to Cook MyoSite (Pittsburgh, PA) for processing, isolation, and propagation of cells. Research patients received approximately 30 intradetrusor injections of 0.5 mL delivered to the bladder, for a total of 15 mL and 125 million AMDC, performed utilizing a flexible cystoscope under direct vision using topical local anesthesia. Follow-up assessments included adverse events and efficacy via voiding diary and urodynamic testing at 1, 3, 6 and 12 months post-injection. An optional second injection was offered at the end of the 6 months visit. 20 patients received the first injection and all 20 patients requested and received a second injection. Median patient age was 65 years old (range 41-82 years). There were 16 male (80%) and 4 female (20%) patients. Etiology included 7 men (35%) with persistent urinary retention after transurethral resection of the prostate for benign prostatic hyperplasia and 13 patients (65%) with idiopathic chronic urinary retention. At the primary outcome time point of 12 months, 11/19 patients (58%) reported a global response assessment (GRA) ≥ 5, showing slight to marked improvement in their UAB symptoms, compared to 6/20 (30%) patients at 3 months post-injection. No serious procedure or treatment-related adverse events occurred. Noted improvements included: decreased post void residual urine volume, increased voiding efficiency, and decreased catheter use. Intradetrusor-injected AMDC as a treatment for UAB was successfully completed in a 20-patient trial without serious adverse event and with signal of efficacy. Cellular therapy may be a promising novel treatment for catheter-dependent chronic urinary retention. A multicenter controlled trial is needed to further assess the promise of regenerative medicine in the treatment of lower urinary tract dysfunction.

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study.

We conducted the first-regenerative medicine cellular therapy for underactive bladder (UAB) in an FDA-approved, compassionate-use IND trial to evaluate treatment safety and potential clinical efficacy of autologous muscle-derived stem cells (AMDC) on a patient with UAB. No study-related adverse events or side effects were reported. In the 1-year follow-up period, the subject denied any gross hematuria, urgency, frequency or infection. A reduction in maximum cystometric capacity from 844 to 663 mL was observed, and the patient was able to void small amounts but continues to require self-catheterization 1 year after AMDC injection. Intradetrusor injection of AMDC is safe, minimally invasive and a promising treatment option for the UAB.

Liposomal bladder instillations for IC/BPS: an open-label clinical evaluation.

PURPOSE: Intravesical instillation of liposomes is a potentially new therapeutic option for subjects with interstitial cystitis/bladder pain syndrome (IC/BPS). The aim of this study was to explore the safety and clinical outcomes of 4 weekly instillations of sphingomyelin liposomes in an open-label cohort of subjects with IC/BPS. METHODS: Fourteen symptomatic IC/BPS subjects were treated with intravesical liposomes once a week for 4 weeks. Safety measurements included laboratory specimen collection, vital signs, post-void residual, and assessment of adverse events (AEs). Efficacy measurements included pain visual analog scales (VAS), voiding diaries, global response assessments (GRAs), and O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI and ICPI). RESULTS: No treatment-related AEs were reported at any time over the course of the study. Urgency VAS scores significantly decreased at 4 weeks (p = 0.0029) and 8 weeks (p = 0.0112) post-treatment. Pain VAS scores significantly decreased at 4 weeks post-treatment (p = 0.0073). Combined ICSI and ICPI scores improved significantly at 4 and 8 weeks (p = 0.002 for both time points) post-treatment. Responses to GRA showed improvement at 4 weeks post-instillation. No significant decrease in urinary frequency was found. CONCLUSIONS: Sphingomyelin liposome instillations were well tolerated in subjects with IC/BPS with no AEs attributed to the test article. Treatment was associated with improvements in pain, urinary urgency, and overall symptom scores. Placebo-controlled clinical trials are needed to assess this potential therapy for IC/BPS.

Novel Therapy with Intravesical Liposomes for Ulcerative Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVES: A Federal Drug Administration-approved, compassionate-use, investigational new drug single-subject trial was conducted to evaluate the safety and clinical outcomes of intravesical instillation of liposomes in a woman with ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: After obtaining informed consent, the 48-year-old woman, diagnosed with ulcerative IC/PBS, received four weekly instillations of intravesical liposomes. Subsequently she was evaluated for 8 weeks post bladder instillation. RESULTS: No side effects or adverse events were reported during the 12 week study period. Voids per day decreased from a baseline of 18 voids per 24 h to 11.3 voids per 24 h at week 3, and 12.6 voids per 24 h at 8 weeks after final instillation. Urgency score also decreased from a pre-instillation mean of 1.75 (out of 10) to 1.07 8 weeks after the final instillation. Bladder ulcers noted by cystoscopy at baseline were absent at the 8 weeks post-treatment and no evidence of bladder inflammation was noted. CONCLUSION: Intravesical liposome instillation is minimally invasive and presents an appealing new treatment for IC/PBS. Prospective trials are needed to assess intravesical liposomes for IC/PBS.

Comparing functional status and community integration in severe penetrating and motor vehicle-related brain injuries.

OBJECTIVE: To examine the functional status of persons surviving a severe penetrating traumatic brain injury (TBI) resulting from a gunshot wound who require inpatient rehabilitation. DESIGN: Data were collected prospectively at 4 different time periods: rehabilitation admission and discharge and year 1 and year 2 postinjury. SETTING: Rehabilitation hospital within a Traumatic Brain Injury Model System. PARTICIPANTS: Forty-five persons with severe penetrating brain injury and 45 persons involved in a motor vehicle crash (MVC). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS), FIM instrument, and Community Integration Questionnaire (CIQ). RESULTS: Results indicated functional improvements for both the penetrating and motor vehicle severe TBI groups on the DRS and the FIM from rehabilitation admission to discharge. Follow-up data at 1 and 2 years postinjury revealed continued improvements on the DRS and FIM measures for both groups, with the greatest improvement in recovery during the first year. In addition, improved community reintegration emerged between 1 and 2 years postinjury for both groups, as measured by the CIQ. There was a small significant difference on the outcome measures between the 2 groups in the course of their recovery. CONCLUSIONS: Persons who survive severe penetrating brain injuries and who require inpatient rehabilitation may show continuing improvement in functioning over time. For persons receiving inpatient rehabilitation services, initial improvement is most likely to occur during the hospital stay and continue postinjury, with the largest improvement in the first year after injury. Community reintegration can also be expected over time. One can expect similar outcomes for individuals who sustain a severe penetrating brain injury and a severe brain injury ensuing from an MVC.