Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial.

BACKGROUND: Detrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men. METHODS: Nine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone. RESULTS: Cell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day. CONCLUSIONS: The results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity. Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021-Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Evaluation of pre-operative bladder contractility as a predictor of improved response rate to a staged trial of sacral neuromodulation in patients with detrusor underactivity.

PURPOSE: Sacral neuromodulation (SNM) is one of the few management options shown to improve outcomes in patients with detrusor underactivity (DU). This original research will investigate if preserved bladder contractility can predict a successful treatment with SNM. METHODS: This is a retrospective study of a prospectively collected database of consecutive patients with DU, who had a staged SNM trial from January 2013 to December 2018, with a minimum of 12 months follow-up. The primary outcome was the success of stage 1 SNM trial. RESULTS: In total, 69 patients with DU were followed. The median age was 67 [interquartile range (IQR) 74-55], median baseline bladder contractility index (BCI) 18 (IQR 67-0), and median post-void residual 200 mL (IQR 300-130). There were 35 patients (51%) that responded to a SNM trial. At a median follow-up of 23 months (IQR 39-12), three were removed for poor efficacy. In patients with detrusor acontractility (DAC), six responded (33%), compared to 29 patients (57%) with BCI > 0. This was statistically significant, p value 0.03. Younger age was also a predictive factor for SNM response, p value 0.02. There were no differences noted in those with gender, neurogenic history, previous pelvic surgery, diabetes, or pre-operative voiding history. CONCLUSION: Our study showed that patients with preserved bladder contractility are more likely to respond to a trial of SNM compared with those that have DAC. Younger age was also predictive of SNM response. UDS is the only method to accurately identify DAC patients. This information will help in patient selection and pre-operative counselling.

New technology assessment and current and upcoming therapies for underactive bladder.

BACKGROUND AND AIMS: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder. METHODS: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB. RESULTS: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria. 2) Should residual urine volume be the primary outcome parameter and how often should it be measured? 3) Are there secondary measures that should have a place in UAB trials, such as change in the number of catheterizations, quality of life measures, etc.? 4) Use and format of bladder voiding and catheterization diary for trials. 5) Define role and technique of urodynamics in UAB trials. Are urodynamics required to monitor, and possibly exclude, individuals with high pressure voiding induced by bladder prokinetic therapies? 6) Development and use of UAB questionnaires. DISCUSSION AND CONCLUSION: The UAB regulatory working group recognizes the path forward should include engaging the FDA and other regulatory organizations that may harmonize and formalize guidance for regulatory trial designs for therapeutics for UAB.

Current concepts of the acontractile bladder.

The acontractile bladder (AcB) is a urodynamic-based diagnosis wherein the bladder is unable to demonstrate any contraction during a pressure flow study. Although it is often grouped with underactive bladder, it is a unique phenomenon and should be investigated independently. The purpose of the present review was to examine the current literature on AcB regarding its pathology, diagnosis, current management guidelines, and future developments. We performed a review of the PubMed database, classifying the evidence for AcB pathology, diagnosis, treatment, and potential future treatments. Over the 67 years covered in our review period, 42 studies were identified that met our criteria. Studies were largely poor quality and mainly consisted of retrospective review or animal models. The underlying pathology of AcB is variable with both neurological and myogenic aetiologies. Treatment is largely tailored for renal preservation and reduction of infection. Although future developments may allow more functional restorative treatments, current treatments mainly focus on bladder drainage. AcB is a unique and understudied bladder phenomenon. Treatment is largely based on symptoms and presentation. While cellular therapy and neuromodulation may hold promise, further research is needed into the underlying neuro-urological pathophysiology of this disease so that we may better develop future treatments.

Saphenous nerve stimulation normalizes bladder underactivity induced by tibial nerve stimulation in cats.

This study in α-chloralose-anesthetized cats aimed at investigating the bladder responses to saphenous nerve stimulation (SNS). A urethral catheter was used to infuse the bladder with saline and to record changes in bladder pressure. With the bladder fully distended, SNS at 1-Hz frequency and an intensity slightly below the threshold (T) for inducing an observable motor response of the hindlimb muscles induced large amplitude (40-150 cmH2O) bladder contractions. Application of SNS (1 Hz, 2-4T) during cystometrograms (CMGs), when the bladder was slowly (1-3 ml/min) infused with saline, significantly ( P < 0.05) increased the duration of the micturition contraction to >200% of the control without changing bladder capacity or contraction amplitude. Repeated application (1-8 times) of intense (4-8T intensity) 30-min tibial nerve stimulation (TNS) produced prolonged post-TNS inhibition that significantly ( P < 0.01) increased bladder capacity to 135.9 ± 7.6% and decreased the contraction amplitude to 44.1 ± 16.5% of the pre-TNS control level. During the period of post-TNS inhibition, SNS (1 Hz, 2-4T) applied during CMGs completely restored the bladder capacity and the contraction amplitude to the pre-TNS control level and almost doubled the duration of the micturition contraction. These results indicate that SNS at 1 Hz can facilitate the normal micturition reflex and normalize the reflex when it is suppressed during post-TNS inhibition. This study provides an opportunity to develop a novel neuromodulation therapy for underactive bladder using SNS.