How to define failure of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) has a major impact on patients' quality of life and can lead to upper urinary tract complications. Intradetrusor botulinum toxin type A injections are administered as second-line treatment to these patients following the failure of anticholinergic agents. The aim of the DETOX 2 study is to propose a consensus definition of the failure of intradetrusor botulinum toxin injections for NDO in patients presenting spinal cord injury, spina bifida, or multiple sclerosis (MS) with self-catheterization. METHOD: This study followed the method adopted by the French National Authority for Health for recommendations by consensus. Based on a review of the literature and a preliminary survey, a steering committee compiled a questionnaire and selected a rating group comprising 16 experts from the Neuro-Urology Committee of the French Urology Association (cnuAFU) and Genulf. The experts were asked to complete the online questionnaire. At the end of the first round, all participants came together to discuss any disagreements and a second-round online questionnaire was completed to reach a consensus. RESULTS: Thirteen of the 16 experts approached completed both rounds of questionnaires. A strong consensus was reached for two proposals (median score = 9/10) which were therefore included in the definition from the first round: at least one repeat injection of the same botulinum toxin at the same dose must be given to rule out failure on technical grounds and a duration of efficacy <3 months must be considered a failure. At the end of round 2, a relative consensus was reached regarding the clinical criterion defining failure (median score = 7/10) and the urodynamic criterion of failure (median score = 8/10). An additional proposal was selected during this second round on the need for a voiding diary (median score = 8/10). CONCLUSION: The first consensus definition of failure of an intradetrusor injection of TB-A for NDO has been achieved with this study: persistence of detrusor overactivity with maximum detrusor pressures >40 cm H2O and/or a compliance issue and/or persistence of urinary incontinence and/or urgency and/or a number of daily self-catheterizations >8/day and/or efficacy <3 months. This study will help to standardize research on the failure of the intradetrusor botulinum toxin for NDO in clinical practice and clinical research.

Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation-A study from the neuro-urology committee of the French Association of Urology.

BACKGROUND: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). OBJECTIVES: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. METHODS: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. RESULTS: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing-remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. CONCLUSION: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Long Term Effectiveness and Safety of Intracavernosal Botulinum Toxin A as an Add-on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 Injections for Erectile Dysfunction.

BACKGROUND: Some evidence suggests that intracavernosal botulinum toxin A (BTX-A IC) injections administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandin E1 intracavernosal injections (PGE1 ICI) could effectively treat erectile dysfunction (ED) in non-responders, or insufficient responders to these pharmacologic treatments. AIM: To determine the long-term effectiveness and safety of combined treatment involving a single injection of BTX-A IC as an add on therapy to PDE5-Is or PGE1-ICI for the treatment of ED of different etiologies. METHODS: A retrospective, uncontrolled, single center study was conducted. Data from 123 consecutive patients with ED who were insufficient responders to PDE5-Is or PGE1-ICI and who received onabotulinumtoxinA 100 U, abobotulinumtoxinA 250 U or 500 U IC as an add on to their current pharmacologic treatment were analyzed. All analyses were exploratory. Qualitative data were compared using the Fisher's exact test. Univariate and multivariate analysis were performed using logistic regression with Odds Ratios (OR). Only variables with P < .05 in the univariate analysis were selected for multivariate analysis. RESULTS: The minimally clinically important difference (relative to baseline severity of ED) in the International Index of Erectile Function-Erectile function domain (IIEF-EF) score was achieved in 50% of patients at 34 (27-42) days and in 41% at 5.9 (3.9 - 8.1) months following BTX-A IC in combination with PDE5-Is or PGE1 ICI. The severity of ED influenced response to BTX-A IC according to the multivariate analysis (OR = 0.3, IC(95%]) = (0.16 - 0.56). Neither being post prostatectomy nor the type of BTX-A affected the response. Effectiveness tended to decrease more over time with abobotulinumtoxinA 250 U than 500 U. The only side-effects were mild penile pain on injection (n = 1) and mild penile pain for 3 days following injection (n = 1); no systemic effects were reported. CLINICAL IMPLICATIONS: BTX-A IC (all types) administered as an add on to registered pharmacologic treatments improved erectile function for at least 6 months in 41% of patients with ED of varying etiologies, and was safe. STRENGTHS & LIMITATIONS: A relatively large cohort of patients with ED was included, with a long follow-up period, however the study was retrospective, and uncontrolled. CONCLUSION: This study provides preliminary evidence that BTX-A IC administered as an add-on therapy for ED that is insufficiently responsive to standard therapy is effective for at least 6 months, and is safe. Randomized clinical trials are now needed to fully confirm these results. Giuliano F, Joussain C, Denys P, Long Term Effectiveness and Safety of Intracavernosal Botulinum Toxin A as an Add-on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 Injections for Erectile Dysfunction. J Sex Med 2022;19:83-89.

Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats.

BACKGROUND: Botulinum toxin A (BTX-A) has a variety of uses in medicine. Some evidence suggests that intracavernosal (ic) BTX-A injection administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) could effectively treat erectile dysfunction (ED) in insufficient responders to PDE5-Is. AIM: To provide experimental pharmacological evidence for the use of onabotulinumtoxinA ic alone or in combination with PDE5-Is for difficult-to-treat ED. We thus compared the effects of BTX-A ic alone and BTX-A ic combined with PDE5-I iv, and a placebo treatment ic or iv. METHODS: Erectile function was evaluated following cavernous nerve electrical stimulation (6 V, 1-millisecond pulse, 45-second duration) at different frequencies (0, 2, 3, 4, 5, 7.5, and 10 Hz) in 4 groups (n = 8 / group) of anesthetized, spontaneously hypertensive rats, a robust animal model of ED of vascular origin. Rats were treated by onabotulinumtoxinA 10U or saline ic 1 week prior to erectile function testing and sildenafil (0.3 mg/kg) or saline iv 4 minutes prior to testing. Frequency-response curves were compared with a 2 way ANOVA. OUTCOMES: Both onabotulinumtoxinA ic, and sildenafil iv significantly improved erectile responses in spontaneously hypertensive rats, however the effect was greatly amplified when the treatments were combined. RESULTS: Intracavernosal pressure and/or mean arterial pressure ratios were significantly increased by sildenafil and onabotulinumtoxinA ic versus the control condition. OnabotulinumtoxinA 10U ic combined with sildenafil iv significantly potentiated erectile responses. Area under the curve and/or mean arterial pressure ratio increased by 19% with sildenafil iv, by 15% with onabotulinumtoxinA ic and by 58% with the combined treatment following cavernous nerve electrical stimulation at 6V, 1 ms, 10 Hz: these stimulation parameters elicited the maximal erectile response. CLINICAL TRANSLATION: These data provide a pharmacological rationale for the combined administration of onabotulinumtoxinA ic and sildenafil iv since the effects of both treatments were potentiated when their administration was combined. STRENGTHS & LIMITATIONS: First evidence of a synergistic pro-erectile effect of BTX-A combined with PDE5-I, however the mechanism behind the pro-erectile effect of BTX-A ic remains hypothetical. CONCLUSIONS: These results support further studies into the mechanisms behind the pro-erectile effect of BTX-A ic, as well as multicenter randomized control trials to evaluate the safety and efficacy of BTX-A ic combined with sildenafil for difficult-to-treat ED. Giuliano F., Joussain C., Denys P., et al. Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats. J Sex Med 2022;19:899-906.

Prioritization of risk situations in neuro-urology: guidelines from Association Française d'Urologie (AFU), Association Francophone Internationale des Groupes d'Animation de la Paraplégie (A.F.I.G.A.P.), Groupe de Neuro-urologie de Langue Française (GENULF), Société Française de Médecine Physique et de Réadaptation (SOFMER) and Société Interdisciplinaire Francophone d'UroDynamique et de Pelvi-Périnéologie (SIFUD-PP).

PURPOSE: The current health crisis has drastically impacted patient management in many fields, including neuro-urology, leading to a mandatory reorganization. The aim of this work was to establish guidelines regarding the prioritization and optimal timing of each step of neurogenic lower urinary tract dysfunction management. METHODS: A steering committee included urologists and physical medicine and rehabilitation practitioners. Based on a literature review and their own expertise, they established a comprehensive risk-situation list and built a risk scale, allowing multiple other experts to score each clinical situation. New recommendations were generated using a Delphi process approach. RESULTS: Forty-nine experts participated in the rating group. Among the 206 initial items, 163 were selected and divided into four domains, diagnosis and assessment, treatment, follow-up, and complications, and two sub-domains, general (applicable for all neurological conditions) and condition-specific [varying according to the neurological condition (spinal cord injury, multiple sclerosis, brain injury, Parkinsonism, dysraphism, lower motor neuron lesions)]. The resulted guidelines are expert opinions established by a panel of French-speaking specialists, which could limit the scalability of this work. CONCLUSIONS: The present multidisciplinary collaborative work generates recommendations which complement existing guidelines and help clinicians to reorganize their patients' list in the long term with a personalized medicine approach, in the context of health crisis or not.

Predictive factors of diagnostic and therapeutic divergence in a nationwide cohort of patients seeking second medical opinion.

OBJECTIVES: The aim of this study was to describe the profile of patients who sought a second medical opinion (SMO) on their therapeutic or diagnostic strategy using nationwide data from a French physician network dedicated to SMOs. METHODS: An observational cohort study was conducted and the study population consisted of patients residing in France or in the French overseas territories who submitted a request for an SMO through a dedicated platform between January 2016 and October 2020. Patient characteristics were compared between convergent and divergent SMOs. The divergent rate for all patients excluding those with mental diseases were described. Logistic regression was used to estimate the probability of a divergent SMO according to patient characteristics. RESULTS AND DISCUSSION: In total, 1,552 adult patients over several French regions were included. The divergence rate was 32.3 % (n = 502 patients). Gynecological [Odds Ratio (OR) and 95 % CI: 5.176 (3.154 to 8.494)], urological [OR 4.246 (2.053 to 8.782)] and respiratory diseases [OR 3.639 (1.357 to 9.758)] had the highest probability of a divergent SMO. Complex cases were also associated with a significantly higher risk of a divergent opinion [OR 2.78 (2.16 to 3.59)]. Age, sex, region and profession were not found to be predictive of a divergent second opinion. CONCLUSIONS: Policymakers should encourage new research on patient outcomes such as mortality and hospitalization rates after a SMO. When proven effective, SMO networks will have the potential to benefit from specific public funding or even play a key role in national healthcare quality improvement programs.

Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial.

BACKGROUND: Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. METHODS: Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. RESULTS: Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5-2.5) in the WOCA group versus 2.5 (1.2-4.0) (P = .0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P < .001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0-2.0) versus 3.0 (2.0-5.0) (P = .004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. CONCLUSIONS: WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. CLINICAL TRIALS REGISTRATION: NCT01388413.

Outcomes of ileal conduit urinary diversion in patients with multiple sclerosis.

AIM: The objective of this study was to report the long-term outcomes and complications of patients with multiple sclerosis (MS) who underwent noncontinent urinary diversion to treat lower urinary tract symptoms (LUTS). MATERIAL AND METHODS: A retrospective study included all adult patients with MS who underwent an ileal conduit urinary diversion between 2000 and 2015. Early postoperative complications were reported as well as long-term complications, reoperation rates, and renal function. RESULTS: Overall, 91 patients were included. The surgery was indicated for refractory urinary incontinence (n = 73), renal failure (n = 8), major perineal skin ulcer due to urinary incontinence (n = 6), and recurrent urinary tract infections (n = 4). The median follow-up was 50 months (range, 3-158 months). A significant reduction (P < .05) of postoperative nonobstructive pyelonephritis rate was observed. There was no significant difference between preoperative and postoperative renal function (P = .32). Early postoperative complications were reported in 24 patients (26%): 4 Clavien I, 6 Clavien II, 9 Clavien III, 4 Clavien IV, and 1 Clavien V. Nine patients required reoperation for these complications (9.9%). Late complications were reported in 28 patients (30.8%): 8 ureteral anastomosis stenosis, 2 stoma stenosis, 2 incisional hernias, 6 kidney or ureteral lithiasis, and 10 pyelonephritis. Among them, 15 patients (16.5%) required reoperation for late complications. CONCLUSION: Noncontinent urinary diversion using ileal conduit appears to be an effective end-stage solution in MS patients. The perioperative morbidity rate of 26% and the late complication rate of 31% should be considered to better inform patients before the surgery.

Urological dysfunction in patients with hereditary spastic paraplegia.

AIMS: Purposes of this study were to describe lower urinary tract symptoms (LUTS) and related urodynamic patterns in patients with hereditary spastic paraplegia (HSP), and to characterize LUTS management and associated uronephrological complications. METHODS: We retrospectively reviewed medical files of HSP patients, consecutively followed in our Physical and Rehabilitation Medicine Department between 1999 and 2016. Clinical, urodynamic, and radiological data were collected and analyzed. Different treatments which have been prescribed and uronephrological complications were also recorded. Patients with other neurological or urological diseases were excluded. RESULTS: Thirty-three patients with HSP were included. Mean duration of follow-up was 8.1 ± 5 years, mean age 62 ± 14 years, and 70% were men. The most frequent LUTS was urgency and voiding dysfunction (both 69.7%). Incontinence and retention with a significant postvoid residue above 100 mL accounted for 66.7% and 57.6% of initial symptoms respectively. Neurogenic detrusor overactivity was diagnosed in 80.7% of patients. Two-thirds of our cohort were treated with anticholinergics and 9.1% required intradetrusor botulinum-toxin injections. Only 27.3% of patients performed clean intermittent self-catheterization. Febrile urinary tract infections (21.2%), urolithiasis (15,1%), hydronephrosis (6%), and chronic renal failure (9.1%) were found. CONCLUSION: Given their high prevalence and the risk of uronephrological complications, LUTS should be systematically assessed in HSP patients. The systematic screening of urological dysfunction in this population would improve its management, decrease the incidence of uronephrological complications, and increase the quality of life.

Long-term functional outcomes of augmentation cystoplasty in adult spina bifida patients: A single-center experience in a multidisciplinary team.

AIM: To report the very long-term functional outcomes of augmentation cystoplasty (AC) in adult spina bifida patients. METHODS: All consecutive adult spina bifida patients who underwent AC between 1991 and 2008 were enrolled. Early postoperative complications (Clavien-Dindo classification) and long-term outcomes (voiding modalities, urodynamic parameters, renal function, continence, and quality of life) were assessed. RESULTS: Twenty-eight patients with a median age of 20 years (IQR 17-25) were included. They all underwent AC with a supratrigonal cystectomy (SC). The median follow-up was 13.6 years (IQR 6-16.5). Thirteen early postoperative complications (12 grade I-II, 1 grade III) were observed in 11 patients (39%). Eight patients (29%) had upper urinary tract infections managed with antibiotics, with 2 patients requiring ureteral stents. Bladder stones occurred in 2 patients (7%) and were managed with endoscopy and cystostomy. One bladder perforation was reported. One bladder cancer was observed 26 years after surgery. Creatinine clearance and all urodynamic parameters were significantly improved post-operatively. The overall complication and reoperation rates were 57% and 14%, respectively. At last follow up, the continence rate was 71% (n = 20), with 93% (n = 26) performing intermittent self-catheterization. Quality of life was improved for 71% of patients. CONCLUSION: In adult spina bifida population, AC is a high-risk procedure with an overall complication rate of 57% and a reoperation rate of 14%. However, AC is beneficial to the overall health of the patients since it provides a satisfying continence rate, an improvement of quality of life, and long-term protection of the upper urinary tract.

Predictive factors of adherence to urinary self-catheterization in older adults.

AIMS: The primary aim is to explore the adherence predicting factors in clean intermittent self-catheterization (CISC) in patients aged over 65 years. The secondary aim is to assess whether in this population, the non-adherence risk is greater, compared with patients under 65. METHODS: All patients older than 65 that successfully learned CISC between January 2011 and January 2016 were included. A control population younger than 65 matched with sex, body mass index, and pathology was selected. RESULTS: One hundered and thirteen (66.9%) out of the 169 patients older than 65 included were adherent at 1 month, and 80 (47.3%) at 6-12 months. Obesity (P = 0.027), a low PP test (Pencil and Paper test) score (P = 0.037), significant urinary stress incontinence (SUI) (P = 0.048), and prescription of CISC less than three per day (P = 0.03) were the risk factors predicting stopping CISC at 1 month, but none was associated with non-adherence at 6-12 months. Compared with the younger group, age was a risk factor for poor adherence at 1 month. CONCLUSION: Obesity, low PP test score, and important SUI are factors of poor adherence to CISC at 1 month in older adults. Necessity of more than three CISC per day is in favor of treatment continuation, possibly due to absence of spontaneous voiding in these patients. Long-term adherence to CISC in older adults in this study remains close to adherence to other treatments prescribed in urinary disorders, and thus shows that CISC could be an easily purposed therapeutic option in this population, either on a long-term or transitory basis.

Management of urethrocutaneous fistulae complicating sacral and perineal pressure ulcer in neurourological patients: A national multicenter study from the French-speaking Neuro-urology Study Group and the Neuro-urology committee of the French Association of Urology.

PURPOSE: To describe the epidemiologic characteristics of urethrocutaneous fistulae (UCF) in sacro-perineal pressure ulcer (SPPU) in neurourological patients and to assess outcomes after surgical urinary diversion. MATERIALS AND METHODS: Through the French-speaking Neurourology Study Group and Association of Urology network, a retrospective multicenter study in nine major urology and physical medicine and rehabilitation (PMR) units was conducted. All patients with SPPU associated with UCF between 2000 and 2016 were included. Data concerning: sociodemography, clinical, medical and biological comorbidities, neurological and urological history, pressure ulcer characteristics, and finally urinary diversion surgery were collected. Complications and SPPU healing/relapse were assessed. RESULTS: In all, 74 patients were included. The median age on diagnosis: 45.9 years (interquartile range [IQR], 38.7-53.4) and median follow-up: 15.1 months (IQR, 5.7-48.8). A psychiatric disorder was the most frequent comorbidity (44.6%). Only 59.5% and 50% had regular PMR and urologic follow-up, respectively. Seventy-one patients (95.9%) underwent urinary diversion surgery. Among those, relapse occurred in 15 (21.1%) at the end of the follow-up. The diversion was noncontinent in 85.9%. The major complications rate was 26.8%. A total of 30 late complications in 21 patients were reported. The most frequent was obstructive pyelonephritis (n = 9). All of the patients who underwent surgical diversion without cystectomy (n = 5) developed a pyocyst. Finally, the pressure ulcer healing rate when patients underwent both urinary diversion and pressure ulcer surgery was 74.4%. CONCLUSIONS: Our retrospective data suggest that UCF complicating SPPU is a rare and severe pathology. The combination of radical urinary diversion with cystectomy and pressure ulcer surgery should be performed as often as possible.

Neurogenic stress urinary incontinence: is there a place for Adjustable Continence Therapy (ACT™ and ProACT™, Uromedica, Plymouth, MN, USA)? A retrospective multicenter study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To assess the effectiveness and complications of treatment for neurogenic stress urinary incontinence (nSUI) by Adjustable Continence Therapy (ACT™ and ProACT™). SETTING: France. METHODS: A retrospective multicentre study of consecutive patients with neurological pathologies treated for nSUI with ACT balloons. RESULTS: From January 2001 to January 2013, 102 patients were implanted. Mean (SD) age at implantation was 48.4 (16.5) years. Patients were followed-up for a mean 2.7 (2.3) years. After implantation, 5.9% of patients were totally continent, 51.2% had an improvement in symptoms of at least 50% (including 14.6% with improvements of at least 90%), and 48.8% had improvements of < 50%, including 7.3% of treatment failures. Complications occurred in 70 patients (120 balloons): 21 balloon infections, 34 migrations, 18 device failures, 28 urethral erosions and 28 cutaneous erosions. The procedure was ineffective for 35 patients. Twenty patients underwent permanent explantation. The rate of migrations was lower in patients with upper motor neuron lesion than in those with lower motor neuron lesion (p = 0.04). CONCLUSIONS: ACT is a minimally invasive treatment for SUI related to sphincter deficiency. This is one of the first reports in a sample of patients with neurological disorders implanted by multiple surgeons. ACT could be a less invasive, appropriate alternative to artificial urinary sphincters. However, it is associated with frequent local complications which are easy to manage but that should be reduced in this challenging population.

Intradetrusor Injections of Botulinum Toxin A in Adults with Spinal Dysraphism.

PURPOSE: The aim of the current study was to determine the outcomes of botulinum toxin A intradetrusor injections in adult patients with spina bifida. MATERIALS AND METHODS: All patients with spinal dysraphism who underwent intradetrusor injections of botulinum toxin A from 2002 to 2016 at a total of 14 centers were retrospectively included in analysis. The primary end point was the global success of injections, defined subjectively as the combination of urgency, urinary incontinence and detrusor overactivity/low bladder compliance resolution. Univariate and multivariate analysis was performed to seek predictors of global success. RESULTS: A total of 125 patients were included in study. The global success rate of the first injection was 62.3% with resolution of urinary incontinence in 73.5% of patients. All urodynamic parameters had improved significantly by 6 to 8 weeks compared to baseline, including maximum detrusor pressure (-12 cm H2O, p <0.001), maximum cystometric capacity (86.6 ml, p <0.001) and compliance (8.9 ml/cm H2O, p = 0.002). A total of 20 complications (3.6%) were recorded for the 561 intradetrusor botulinum toxin A injections, including 3 muscular weakness complications. The global success rate of the first injection was significantly lower in patients with poor compliance (34.4% vs 86.9%, OR 0.08, p <0.001). On multivariate analysis poor compliance was associated with a lower global success rate (OR 0.13, p <0.001). Female gender (OR 3.53, p = 0.01) and patient age (OR 39.9, p <0.001) were predictors of global success. CONCLUSIONS: Intradetrusor botulinum toxin A injections were effective in adult patients with spina bifida who had detrusor overactivity. In contrast, effectiveness was much lower in adult patients with spina bifida who had poor bladder compliance. The other predictors of global success were female gender and older age.

Human spinal ejaculation generator.

OBJECTIVE: A spinal ejaculation generator (SEG) has been identified in the rat with lumbar galaninergic interneurons playing a pivotal role (Science 2002;297:1566-1569). The aim was to evidence a SEG in humans. METHODS: Spatial distribution of galaninergic neurons was studied in postmortem spinal cord segments of 6 men and compared with that of 6 women for evidencing sexual dimorphism. Based on the identified segmental distribution of galaninergic neurons, the ability for penile vibratory stimulation (PVS) to elicit ejaculation when the concerned spinal segments were injured was studied in 384 patients with clinically complete spinal cord injury (SCI) and consequent anejaculation. Such patients represent a unique model to investigate the role of defined spinal segments in the control of ejaculation. RESULTS: Galaninergic neurons were mostly located between L2 and L5 segments in medial lamina VII, with a maximal density within L4. Three-dimensional 3D reconstruction showed that these neurons were grouped into single columns bilaterally to the central canal. In addition, galaninergic neuron density was found higher in L3 and L4 segments in men as compared to women supporting sexual dimorphism. In the patients' cohort, injury of L3-L5 segments was the sole independent predictor for failure of PVS to induce ejaculation. Although evidence from clinical observations was indirect, there is close correspondence to neuroanatomical data. INTERPRETATION: Organization and sexual dimorphism of human spinal galaninergic neurons were similar to the rat's SEG. Neurohistological data, together with clinical results, corroborate the existence of an SEG in humans in L3-L5 segments. Such a generator could be targeted to treat neurogenic and non-neurogenic ejaculatory disorders. ANN NEUROL 2017;81:35-45.

Long-term outcomes and risks factors for failure of intradetrusor onabotulinumtoxin A injections for the treatment of refractory neurogenic detrusor overactivity.

AIMS: Aims of this study were to assess the long-term outcomes of Intradetrusor injection of OnabotulinumtoxinA (Botox® injection) associated with clean intermittent-catheterization (CIC) for the treatment of neurogenic detrusor overactivity (NDO) and to identify risk factors for failure. METHODS: Neurological patients with NDO using CIC who had received Botox® injections between January 2001 and September 2013 were included. Clinical, urodynamic and radiological data were recorded. Primary endpoint was failure and withdrawal rates after 3, 5, and 7 years of management. Survival curves of withdrawals and failures of treatment were calculated with a 95-confidence interval using the Kaplan-Meier method. Risk factors for failure were determined with univariate analysis and multivariate analysis using Cox model. RESULTS: Overall, 292 patients, mean age of 40 ± 13, 6 years, were included. Overall, 219 patients (80.6%; IC95% [76.3-85.4%]) were still treated with Botox® injections after 3 years, 128 (71.1%; IC95% [65.7%, 76.9%]) after 5 years, and 58 (60.8%, IC95% [54.0%, 68.4%]) after 7 years. Failure rate was 12.6% (IC95% [8.6-16.5%]) after 3 years, 22.2% (IC95% [16.6-27.3%]) after 5 years, and 28.9% (IC95% [21.9%; 35.3%]) after 7 years of follow-up. Withdrawal rate after 7 years of follow-up was 11.3% (n = 33/292). Severe NDO at baseline appears to be a significant risk factor for failure. CONCLUSION: This study confirms long-term efficacy and tolerance of Botox® injection in patients with NDO using CIC. Long-term failure and withdrawal rates remain low but significant, and need to be managed.

Complications of non-continent cutaneous urinary diversion in adults with spinal cord injury: a retrospective study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To report the long-term complications of non-continent cutaneous urinary diversion (NCCUD) in adult patients with spinal cord injury (SCI). SETTING: Hospital in Paris, France. METHODS: A retrospective single center study included all adult patients with SCI who underwent an ileal conduit between 1997 and 2014. Early complications were reported according to Clavien-Dindo classification. Long-term complications and reoperation rates were recorded, as well as stoma management and autonomy improvement related to urinary function. RESULTS: One hundred and two patients were included. The surgical indications included failure of intermittent catheterization (n = 43), urethral fistulae due to skin ulcers (n = 50), renal failure (n = 8), recurrent urinary tract infections (n = 9), lithiasis (n = 3), and bladder tumors (n = 2). There were 67 early postoperative complications for 44 patients (43%) leading to an additional surgery in 15 cases: 30 grade I-II, 30 grade III, 6 grade IV, and 1 grade V. A total of 37 late complications were reported for 36 patients (35%): 17 ureteral anastomosis stenosis, 3 stoma hernia, 3 pyocystis (3/15 patients), 7 pyelonephritis, 2 renal failures, 2 ureteral lithiasis, 1 uterine prolapse, 1 incisional hernia, and 1 tumor recurrence. Renal function remained unchanged (p = 0.53). Autonomy related to urinary function was improved in 88% of patients. The correct fitting of the stoma was possible for 81% of the patients. CONCLUSIONS: Despite a perioperative morbidity rate of 43% and a late complication rate of 35%, as a last resort procedure, NCCUD is an end-stage solution in patients with SCI to preserve renal function and achieve autonomy.

Positive outcomes with first onabotulinumtoxinA treatment persist in the long term with repeat treatments in patients with neurogenic detrusor overactivity.

OBJECTIVE: To examine whether response to first treatment with onabotulinumtoxinA is predictive of long-term treatment outcome in patients with neurogenic detrusor overactivity (NDO). PATIENTS AND METHODS: Patients with NDO who were enrolled in a 3-year extension study (after a 52-week phase III study) received onabotulinumtoxinA 'as needed', based on fulfilment of prespecified retreatment criteria. This post hoc analysis included patients who received only the 200-U dose during the phase III and extension studies. Data on mean percent reduction from baseline in urinary incontinence (UI) episodes at week 6 after the first treatment were analysed, and the patients were stratified into three response groups: <50% (group 1; n = 33), 50-74% (group 2; n = 23), and 75-100% (group 3; n = 139). The following were assessed: change from baseline in mean percent UI reduction; proportions of patients who achieved ≥50% and 100% UI reduction after each subsequent treatment, and patients who achieved ≥50% UI reduction after all subsequent treatments; change from baseline in Incontinence Quality of Life (I-QOL) total summary score; and the proportion of patients who achieved or exceeded the minimally important difference (MID; +11 points) in I-QOL score. Adverse events (AEs) were also assessed. RESULTS: The majority of the patients (83.1%; 162/195) experienced a ≥50% UI reduction after onabotulinumtoxinA treatment 1. Baseline characteristics were largely similar across the groups. After treatment 1, the mean percent reduction in UI remained consistent in subsequent treatments 2-6 for patients in response group 2 (range: 64.5-83.5%) and group 3 (range: 79.4-88.0%), but increased for those in the low response group (range: 36.3-60.3%). After treatment 1, the proportion of patients who achieved ≥50% reduction in UI episodes was consistent with subsequent treatments 2-6 in group 2 (range: 75.0-100%) and group 3 (range: 87.3-97.1%), but increased in the low response group (range: 48.3-72.7%). Even among those who achieved a low response after treatment 1, 37.9% of patients achieved ≥50% UI reduction in all subsequent treatments. Improvements in I-QOL scores in groups 2 and 3 were consistently 2-3 times the MID. In the low response group, at least 50% of the patients achieved or exceeded the MID with treatments 2-6. AEs were similar across all response groups and consistent across repeated treatments. CONCLUSION: Patients with NDO with a ≥50% UI reduction after their first onabotulinumtoxinA treatment continued to experience consistent improvements in UI and quality of life with subsequent treatments over the duration of 4 years. A <50% UI reduction after first treatment did not necessarily predict low response with subsequent treatments. Thus, these results underscore the importance of attempting at least a second treatment with onabotulinumtoxinA before deeming patients unsuitable for onabotulinumtoxinA therapy.

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.