Urethral Bulking in the Treatment of Stress and Mixed Female Urinary Incontinence: Results from a Multicenter Cohort and Predictors of Clinical Outcomes.

The aim of the present study is to analyze the outcomes of urethral bulking in the treatment of non-neurogenic female stress and mixed urinary incontinence and to assess predictors of clinical outcomes. We retrospectively included all consecutive patients affected by stress or mixed urinary incontinence and treated with urethral bulking. Outcomes were evaluated via the PGI-I questionnaire and the 24-h pad test. Between January 2010 and January 2020, we treated 216 patients (Bulkamid n = 206; Macro-plastique n = 10). The median age at surgery was 66 years (IQR 55−73.75). The median follow-up was 12 months (IQR 12−24). In total, 23.8% of patients were subjected to prior incontinence surgery, 63.8% of patients were affected by genuine stress urinary incontinence, 36.2% reported mixed urinary incontinence, whereas detrusor overactivity was confirmed in only 24.9%. The dry rate was 32.9%; nevertheless, 69.9% of patients declared themselves "very improved" or "improved" (PGI-I1-2). Low complications were observed, mostly classified as Clavien I. After univariate and multivariate analyses, the only statistically significant independent predictor of "dry" outcome was the 24 h pad test, p < 0.001. Urethral bulking could be proposed with more expectations of success in patients with mild urinary incontinence. Patients affected by moderate−severe incontinence are less likely to obtain clinical success; therefore, they should be carefully counselled about clinical expectations before the procedure.

Can urethral re-bulking improve the outcomes of a prior urethral bulking?

AIMS: To analyze the outcomes of urethral re-bulking in the treatment of female stress urinary incontinence. MATERIALS AND METHODS: We performed a multicenter observational retrospective study, which included all consecutive patients treated with urethral re-bulking for the treatment of persistent stress or mixed urinary incontinence after a previous urethral bulking. Objective outcomes were evaluated with the 24 h pad-test, while PGI-I questionnaires were administered to evaluate subjective outcomes. Clinical outcomes were assessed before re-bulking procedure and at last follow-up. Mann-Whitney's U test was used for subgroup analysis. Shapiro-Wilk's tests were used as normality tests. RESULTS: In total, 62 patients who underwent urethral re-bulking between 2013 and 2020 in a multicenter setting were included. Most patients did not reach complete continence after the first procedure (n = 56) while the remainder reported recurrence of urinary incontinence after initial benefit. Median age at surgery was 66 (IQR: 55-73). Median overall follow-up was 30 months (IQR: 24-41). Median time occurred between the first procedure and reintervention was 12 months (IQR: 7-27). Bulking agents for the re-bulking procedures were bulkamid(n = 56), macroplastique(n = 4), and Prolastic(n = 2). A statistically significant reduction of median 24 h pad test from 100 g(IQR: 40-200) to 35 g(IQR: 0-120) was observed (p = 0.003). Dry rate after rebulking was 36.6%, while 85.4% patients declared themselves 'very much improved' or 'much improved' (PGI-I 1-2). Very few low-grade complications were observed (n = 4). A single case of major complication occurred. CONCLUSIONS: Urethral re-bulking can be an effective technique for the treatment of stress urinary incontinence refractory to a previous urethral bulking and can determine a cumulative benefit after the first procedure.

Efficacy and Safety of Surgical Treatments for Neurogenic Stress Urinary Incontinence in Adults: A Systematic Review.

CONTEXT: Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI). OBJECTIVE: To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management. EVIDENCE ACQUISITION: A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively. CONCLUSIONS: The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques. PATIENT SUMMARY: Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.

Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies.

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra-sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti-muscarinic drugs; secondly, in intra-vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra-cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti-inflammatory treatment could positively influence the disease fate.

Recurrent bacterial symptomatic cystitis: A pilot study on a new natural option for treatment.

OBJECTIVES: The aim of our study was to explore the effectiveness of the combination of D-mannose, Salicin, and Lactobacillus acidophilus (La-14) in patients complaining recurrent symptomatic cystitis due to E. coli. MATERIALS AND METHODS: From July 2013 to September 2014, 85 consecutive subjects (68 women and 17 men) affected by recurrent symptomatic cystitis were enrolled. Of those, 46 (33 women and 13 men) suffered from neurogenic bladder. Overall 78 patients received an initial 5-days regimen consisting on a tid oral combination of 1000 mg of D-mannose plus 200 mg of dry willow extract (salicin) (attack phase), followed by bid 7-days with 700 mg of D-mannose plus 50 mg (1x109 CFU) of Lactobacillus acidophilus (La-14) (maintenance treatment). The maintenance treatment was repeated every 15 days for the next two months. Patients' symptoms were evaluated through a 3-days bladder diary and a Visual Analogic Scale (VAS). RESULTS: After treatment VAS scores decreased from 8.07 ± 1.70 to 4.74 ± 2.07 (p = 0.001) in non-neurological patients (group A) and from 7.21 ± 1.90 to 3.74 ± 3.12 (p = 0.001) in the neurological patients (group B). A significant reduction of daily frequency was noted in both groups: from 14 ± 3 to 7 ± 3 (p = 0.001) in group A and from 15 ± 3 to 8 ± 3 (p = 0.001) in group B. A reduction of incontinence episodes in Group A patients was observed, as well as in 12/39 Group B. Improvements were maintained during follow-up. CONCLUSION: This therapeutic approach combining D-Mannose with Salicin (acute treatment) and Lactobacillus acidophilus La-14 (maintaining treatment) seems to be effective in symptomatic bacterial UTIs. Further larger and randomized control trials (RCTs) are needed to confirm our results.

Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury.

Spinal cord injury (SCI) usually affects younger age groups with male preponderance. The most common traumatic cause is road traffic accident followed by sports accidents and gun-shot injuries. Infections and vascular events make up non-traumatic causes. There is regional variance in incidence and prevalence of SCI. Most systematic reviews have been undertaken from USA, Canada, and Australia with only few from Asia with resultant difficulty in estimation of worldwide figures. Overall, the incidence varies from 12 to more than 65 cases/million per year. The first peak is in young men between 15 and 29 years and second peak in older adults. The average age at injury is 40 years, with commonest injury being incomplete tetraplegia followed by complete paraplegia, complete tetraplegia, and incomplete paraplegia. The bladder function is reliant on both central and peripheral nervous systems for co-ordination of storage and voiding phases. The pathophysiology of bladder dysfunction can be described as an alteration in micturition reflex. It is postulated that a new spinal reflex circuit develops which is mediated by C fibers as response to reorganization of synaptic connections in spinal cord. This is responsible for the development of neurogenic detrusor overactivity (NDO). Various neurotrophic hormones like nerve growth factor affect the morphological and physiological changes of the bladder afferent neurons leading to neuropathic bladder dysfunction. A suprasacral SCI usually results in a voiding pattern consistent with NDO and sphincter dyssynergia. Injury to either the sacral cord or cauda equina results in detrusor hypoactivity/areflexia with sphincter weakness.

Long-term response of different Botulinum toxins in refractory neurogenic detrusor overactivity due to spinal cord injury

ABSTRACT Purpose To assess the response in spinal cord injured patients alternatively treated with different types and dosages of Botulinum neurotoxin type A (BoNT/A) over 15 years. Material and methods Patients who underwent first BoNT/A from 1999-2001 and practiced intermittent catheterization were included. Baseline 3-day bladder diary (BD) and urodynamics were collected. BoNT/A failure was defined when patients asked for re-injection ≤ 3 months post-treatment. Criteria for re-injection was at least one daily episode of urinary incontinence at BD. Before re-injection, patients were asked if they had reached 6 months of dryness without antimuscarinics (YES response). Results Overall, 32/60 (53.4%) "No failure" (NF) group; 16 (26.6%) "occasional failure" (OF) and 12 (20%) "consecutive failure" (CF) were included. A total of 822 BoNT/A infiltrations were performed. The mean interval from previous injection to treatment re-scheduling was 8 months. No significant differences between treatments were found within the three groups (p>0.05). The percentage of YES responses increased from 19% (AboBoNT/A 500IU) to 29 % (OnaBoNT/A 300IU) in NF, and from 18% (AboBoNT/A 500IU) to 25% (OnaBoNT/A 300IU) for OF. Five NF cases (15.6%) maintained 6 months of dryness after each injection. Among the baseline variables, only low compliance (< 20mL/cmH2O) was found as predictor for failure (p=0.006). Conclusions Long term BoNT/A for NDO did not increase failures, independent of the types of treatments and switching. Definition of failure and other criteria for continuing repetitive BoNT/A treatment is mandatory. CF was predictable for no response in earlier follow-up.

Continent catheterizable tubes/stomas in adult neuro-urological patients: A systematic review.

AIMS: To systematically review all available evidence on the effectiveness and complications of continent cutaneous stoma or tube (CCS/T) to treat bladder-emptying difficulties in adult neuro-urological patients. METHODS: The search strategy and studies selection were performed on Medline, Embase, and Cochrane using the PICOS method according to the PRISMA statement (CRD42015019212; http://www.crd.york.ac.uk/PROSPERO). RESULTS: After screening 3,634 abstracts, 11 studies (all retrospective, enrolling 213 patients) were included in a narrative synthesis. Mean follow-up ranged from 21.6 months to 8.7 years (median: 36 months, IQR 28.5-44). At last follow-up, the ability to catheterize rate was ≥84% (except in one study: 58.3%) and the continence rate at stoma was >75%. Data comparing health-related quality-of-life before and after surgery were not available in any study. Overall, 85/213 postoperative events required reoperation: 7 events (7 patients) occurring ≤3 months postoperatively, 22 events (16 patients) >3 months, and 56 events (55 patients) for which the time after surgery was not specified. Sixty additional complications (60 patients) were reported but did not require surgical treatment. Tube stenosis occurred in 4-32% of the cases (median: 14%, IQR 9-24). Complications related to concomitant procedures (augmentation cystoplasty, pouch) included neovesicocutaneous fistulae, bladder stones, and bladder perforations. Risk of bias and confounding was high in all studies. CONCLUSIONS: CCS/T appears to be an effective treatment option in adult neuro-urological patients unable to perform intermittent self-catheterization through the urethra. However, the complication rate is meaningful and the quality of evidence is low, especially in terms of long-term outcomes including the impact on the quality-of-life.

Long-term effectiveness and complication rates of bladder augmentation in patients with neurogenic bladder dysfunction: A systematic review.

AIMS: To systematically evaluate effectiveness and safety of bladder augmentation for adult neuro-urological patients. METHODS: The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement was followed for review of publications. The Medline, Embase, and Cochrane controlled trial databases and clinicaltrial.gov were searched until January 2015. No limitations were placed on date or language. Non-original articles, conference abstracts, and publications involving children and animals were excluded. Risk-of-bias and confounder assessment was performed. RESULTS: A total of 20 studies including 511 patients were eligible for inclusion. The level of evidence for the included studies was low, most level 4 studies with only one level 3 study. The data were narratively synthesized. Across all studies high risk-of bias and confounding was found. Primary outcomes were assessed in 16 of the 20 studies and showed improved quality of life and anatomical changes as well as stable renal function. The secondary outcomes were reported in 17 of the 20 studies and urodynamic parameters and continence all demonstrated improvement after bladder reconstruction. Long-term complications continued up to 10 years post-operatively, including bowel dysfunction in 15% of the patients, stone formation in 10%, five bladder perforations and one bladder cancer. CONCLUSIONS: Available studies are not plentiful and of relatively poor quality, appropriately designed prospective studies are urgently needed. Despite this, bladder augmentation appears to be a highly effective procedure at protecting the upper urinary tract and improving quality of life. However, it is associated with relatively high morbidity in both the short and long term.

Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport® (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study.

AIMS: Assess the efficacy and safety of abobotulinumtoxinA (Dysport®) in adult patients with neurogenic detrusor overactivity (NDO). METHODS: This Phase IIa, international, multicentre, double-blind, randomised, placebo controlled, pilot study enrolled 47 patients with NDO and urinary incontinence resulting from spinal cord injury (SCI) or multiple sclerosis (MS). Patients were treated with 15 intra-detrusor injections of Dysport 750 U or the equivalent placebo (n = 16 and 7) or 30 injections of Dysport 750 U or the equivalent placebo (n = 17 and 7). Primary endpoint was change from baseline in mean number of daily incontinence episode frequency (IEF) at day 84. Secondary endpoints included change from baseline in urodynamic parameters and quality of life (QOL). A safety assessment was also conducted. RESULTS: Adjusted mean changes from baseline in IEF were -3.2 (-76%) and -1.7 (-15%) for 15 injections Dysport and placebo groups, respectively, (P = 0.1103) and -3.2 (-88%) and -2.6 (-73%) for 30 injections Dysport and placebo groups, respectively, (P = 0.0686). Statistically significant improvements in maximum cystometric capacity, maximum detrusor pressure and volume at first contraction were reported in the Dysport groups compared with placebo (P < 0.05). Improvements in QOL were reported. Three muscle weakness episodes were reported as serious adverse events in two tetraplegic and one paraplegic patient, all in the 15 injections Dysport group. CONCLUSIONS: Both 15 and 30 injections administration modes of Dysport decreased daily IEF and resulted in significant improvements in urodynamic parameters in NDO patients with MS or SCI. Reduction to 15 injection sites did not appear to be associated with any impact on efficacy. Neurourol. Urodynam. 36:457-462, 2017. © 2016 Wiley Periodicals, Inc.

Long-Term Efficacy and Safety of OnabotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Who Completed 4 Years of Treatment.

PURPOSE: We assessed the year-to-year consistency of outcomes in patients with urinary incontinence due to neurogenic detrusor overactivity who completed 4 years of onabotulinumtoxinA treatment. MATERIALS AND METHODS: Eligible patients who completed a 52-week phase 3 trial of onabotulinumtoxinA for urinary incontinence could enter a 3-year open label extension study of onabotulinumtoxinA 200 or 300 U administered as needed for symptom control. This analysis focused on 227 patients who completed the 4-year study. Outcomes assessed by year of treatment included mean treatments per year, mean change from baseline at week 6 in urinary incontinence episodes per day and the I-QOL (Incontinence Quality of Life) total summary score, the proportion of patients with 50% or greater and 100% reductions in urinary incontinence episodes per day, duration of effect and adverse events. RESULTS: Patients reported 4.3 urinary incontinence episodes per day at baseline and received 1.4 to 1.5 onabotulinumtoxinA treatments per year. The decrease in urinary incontinence following onabotulinumtoxinA consistently ranged from -3.4 to -3.9 episodes per day across 4 years. A high proportion of patients achieved 50% or greater and 100% urinary incontinence reductions in each year (range 86.6% to 94.1% and 43.6% to 57.4%, respectively). Consistent and clinically relevant improvements in I-QOL scores were observed in each treatment year. The overall median duration of effect of onabotulinumtoxinA was 9.0 months or greater (range 3.0 to 49.2) and 26.0% or more of patients experienced a duration of effect of 12 months or greater. The most common adverse event was urinary tract infection with no increased incidence with time. CONCLUSIONS: Patients with neurogenic detrusor overactivity who completed 4 years of onabotulinumtoxinA treatment experienced a consistent duration of treatment effect and year-to-year improvements in urinary incontinence and quality of life with no new safety signals.

Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well-designed randomised controlled trials are needed to make definitive conclusions. PATIENT SUMMARY: Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Systematic review of surgical treatment of post radical prostatectomy stress urinary incontinence.

Context Stress urinary incontinence (SUI) after radical prostatectomy (RP) continues to be a significant problem with several implications including patient quality of life and other critical postoperative outcomes. Objectives To report the results in terms of efficacy (pad count, 24 hr pad test, QOL questionnaires) and safety (complication rate and type of complications) of all surgical devices approved for the treatment of SUI after RP. Evidence Acquisition A systematic review was conducted in accordance with the PRISMA Statement. A literature search was carried out through the PubMed/Medline, SCOPUS, and Web of Science databases using the keywords "incontinence," "radical prostatectomy," and "'treatment". Inclusion criteria were: number of patients higher than 30, mean follow up longer than 12 months and definition of a successful outcome as the use of 0 to 1 safety pads a day. Evidence Synthesis 113 papers underwent primary review. 51 papers met the inclusion criteria with a total sample size of 4022 patients. Efficacy (0-1 safety pads) was on average 65.7% for AUS, 48.2% for Invance Sling, 48.8% for Advance Sling, 64.2% for ProACT. Twenty four hour pad test and QOL questionnaires were respectively available only in 4 and 18 studies. The overall complication rate was 19.43% for AUS, 7.4% for Invance Sling, 12.3% for Advance Sling, 12.3% for ProACT. Authors' Conclusions Due to the poor overall quality of available studies, it was impossible to identify or refute clinically important differences between the alternative surgical procedures. Although our data seems to suggest that AUS has the highest efficacy in the treatment of SUI following RP it is also associated with the highest complication rate, but this may be due to the longest follow up. Larger rigorous trials are needed in order to support this evidence. Neurourol. Urodynam. 35:875-881, 2016. © 2015 Wiley Periodicals, Inc.

Urodynamics useless before surgery for female stress urinary incontinence: Are you sure? Results from a multicenter single nation database.

AIMS: The role of urodynamics (UDS) before surgery for stress urinary incontinence (SUI) remains a debated issue in female urology as well as in urogynaecology and it has been recently questioned on the basis of data coming from selected population of patients defined as "uncomplicated." The aim of this study was to investigate the percentage of "uncomplicated" patients undergoing urodynamic evaluations in six referral Italian centers. The secondary aim was to assess the prevalence of women, for whom the urodynamic evaluation could add new information to the pre-urodynamic picture and in how many cases these findings had a significant impact on patient management. METHODS: The data of women who underwent urodynamic evaluation prior to surgery for stress urinary incontinence between 2008 and 2013 were retrospectively analyzed. According to the definition of the Value of Urodynamic Evaluation (ValUE) trial criteria, patients presenting with SUI were classified as "uncomplicated" or "complicated." Urodynamic observations were then compared with pre-urodynamic data. RESULTS: Overall, 2,053 female patients were considered. Only 740/2,053 (36.0%) patients were defined "uncomplicated" according to the definition used in the ValUE trial. The urodynamic observations were not consistent with the pre-urodynamic diagnosis in 1,276 out of 2,053 patients (62.2%). Voiding dysfunctions were urodynamically diagnosed in 394 patients (19.2%). Planned surgery was cancelled or modified in 304 patients (19.2%), due to urodynamic findings. CONCLUSIONS: "Uncomplicated" patients represent a minority among female SUI patients evaluated before surgery. In "complicated" patients, the role of urodynamic has not been challenged yet and UDS seems still mandatory. Neurourol. Urodynam. 35:809-812, 2016. © 2015 Wiley Periodicals, Inc.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY: Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1) expression in the urothelium of patients with neurogenic detrusor overactivity.

OBJECTIVE: To investigate the expression of two types of cation channels, γEpithelial Na(+) Channel (γENaC) and the Acid-Sensing Ion Channel 1 (ASIC1), in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, urodynamic parameters were collected and correlated to the immunohistochemical results. PATIENTS SUBJECTS AND METHODS: Four controls and 12 patients with a clinical diagnosis of NDO and suprasacral spinal cord lesion underwent urodynamic measurements and cystoscopy. Cold-cup biopsies were frozen and processed for immunohistochemistry and Western Blot. Spearman's correlation coefficient between morphological and urodynamic data was applied. One-way anova followed by Newman-Keuls multiple comparison post hoc test was applied for Western Blot results. RESULTS: In the controls, γENaC and ASIC1 were expressed in the urothelium with differences in their cell distribution and intensity. In patients with NDO, both markers showed consistent changes either in cell distribution and labelling intensity compared with the controls. A significant correlation between a higher intensity of γENaC expression in the urothelium of patients with NDO and lower values of bladder compliance was detected. CONCLUSIONS: The present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Notably, while the changes in γENaC might impair the mechanosensory function of the urothelium, the increase of ASIC1 might represent an attempt to compensate for the excess in local sensitivity.

Telocytes subtypes in human urinary bladder.

Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRα, αSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location. PDGFRα/calret-positive, CD34/c-Kit-negative TC were located in the sub-urothelium and distinct in two subtypes whether, similarly to myofibroblasts, they were αSMA-positive and had attachment plaques. The sub-urothelial TC formed a mixed network with myofibroblasts and were close to numerous nerve endings, many of which nNOS-positive. A third TC subtype, PDGFRα/αSMA/c-Kit-negative, CD34/calret-positive, ultrastructurally typical, was located in the submucosa and detrusor. Briefly, in the human bladder, we found three TC subtypes. Each subtype likely forms a network building a 3-D scaffold able to follow the bladder wall distension and relaxation and avoiding anomalous wall deformation. The TC located in the sub-urothelium, a region considered a sort of sensory system for the micturition reflex, as forming a network with myofibroblasts, possessing specialized junctions with extracellular matrix and being close to nerve endings, might have a role in bladder reflexes. In conclusions, the urinary bladder contains peculiar TC able to adapt their morphology to the organ activity.

Female sexual dysfunction and hormonal status in multiple sclerosis patients.

INTRODUCTION: Literature holds no information on a correlation between blood hormonal levels, in particular sex hormones and the sexual response of women with multiple sclerosis (MS). AIM: To investigate a possible correlation between hormonal status and the sexual response of females with MS. MAIN OUTCOME MEASURES: The Female Sexual Function Index (FSFI) questionnaire was used to determine sexual dysfunctions (SDs). Methods for measuring blood hormones were chemiluminescence immunoassay, electrochemiluminescence immunoassay, enzyme immunoassay, and radioimmunoassay. METHODS: During the screening phase, 55 women of reproductive age were recruited and completed the FSFI. In the first phase of the study females underwent a hematic hormonal evaluation on the third day of their menstrual cycle. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, 17[alpha]-hydroxyprogesterone, total and free testosterone, 17 beta estradiol, inhibin and sex hormone binding globulin (SHBG), and thyroid hormones (fT3 and fT4) were checked. On the day 20-21 into their menstrual cycle the progesterone hematic value was noted. Patients with amenorrhea had all hormones tested once with a random blood drawing. After a 3-month period patients began phase 2, completing the FSFI again. The same blood hormones were investigated. RESULTS: Fifty-four females completed the study. Thirty-one continued to manifest at least one SD: desire (57.4%) was the most common. Overall, 36.4% showed abnormal hormonal alterations. The most frequent was 40% for 17 beta-estradiol. None of the FSFI domains, including the total score, revealed any statistically significant correlation to the hormones investigated. No statistically significant clinical predictive factors for blood hormone abnormalities were detected; comparing females with and without SD, P = 0.250 using chi-squared test was reached. CONCLUSIONS: Notable percentages of blood hormonal alterations and SD were documented, but no significant statistical correlations were detected between hormonal status and sexual function.

Sexual dysfunction in women during dialysis and after renal transplantation.

INTRODUCTION: Disorders of the reproductive system and menstrual abnormalities often associated with loss of libido and inability to reach orgasm are common in adults of both sexes with an end-stage renal disease. These symptoms may significantly contribute to depression and reduce the sexual activity of women. AIM: To determine if sexual function, as well as hormonal status, improves after kidney transplantation, comparing a group of pre-menopausal women during dialysis and after a successful renal transplantation. METHODS: We enrolled 58 women that received kidney transplantation. Patients included were 18-45 years old, on hemodialysis for more than 6 months following a fully functioning kidney transplantation, and on a stable corticosteroids immunosuppressive regimen for at least 6 months. All women underwent a general and urogynecological examination, a hormonal profile determination, and filled out the Female Sexual Function Index (FSFI) and a Beck Depression Inventory questionnaire administered during dialysis and 12 months after transplantation. MAIN OUTCOME MEASURES: We evaluated the prevalence of Female Sexual Dysfunction according to the FSFI cutoff points, sexual hormonal status, and menstrual status during dialysis and 12 months after kidney transplantation. RESULTS: Nineteen out of 58 women left the study prematurely. Thirty-nine women (mean age 36 +/- 5.9 years) completed the study. A total of 74% of the patients had menstrual disturbances during dialysis, as opposed to 45% after transplantation (P < 0.001). Sixteen out of 39 (41%) patients acknowledged having an active sexual life during dialysis. Thirty-four out of 39 (88%) transplanted patients acknowledged having an active sexual life (Fischer's exact test P = 0.000039). The hormonal profile and FSFI results improved significantly after transplantation. CONCLUSION: This study demonstrates that a successful transplantation should improve the sexual life in women with chronic renal failure.