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.

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.

Efficacy and safety of intradetrusor botulinum toxin injections for idiopathic overactive bladder syndrome in patients with an artificial urinary sphincter.

PURPOSE: To assess the efficacy and safety of intradetrusor botulinum toxin type A injections (IBTI) for idiopathic overactive bladder (iOAB) in non-neurological adults with an artificial urinary sphincter (AUS). MATERIALS AND METHODS: We retrospectively selected, in the 11 French centers, members of a collaborative network (GENULF (Groupe d'étude de neuro-urologie de langue francaise)), the patients who had had an artificial urinary sphincter implantation and who had subsequently developed iOAB requiring IBTI. This study was approved by the French association of urology ethics committee (no 2018012). RESULTS: Between 2006 and 2020, 33 patients were included from 5 French centers. Mean follow-up after the first IBTI was 47 months. The average age of the studied population was 68 years, with 70% of females. A complete resolution of symptoms at optimal IBTI dose was experienced by 21 (64%) patients. Seven (21%) patients had partial improvement. Five non-responder patients (15%) had no improvement at all. Maximum cystometric bladder capacity was 240 ml pre-IBTI and 335 ml post IBTI. Discontinuation free survival at 60 months was 50%. Two erosions occurred during the 6 months following an IBTI both in male patients with a perineal implantation. There were four AUS balloon perforations that occurred during the 6 months following an IBTI, all of them in female patients. CONCLUSIONS: IBTI has a good efficacy for the treatment of iOAB in patients with an AUS. However, both patients and practicians must be aware of the risk of rare and usually mild complications.

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.

Impact of COVID-19 pandemic on functional urology procedures in France: a prospective study.

PURPOSE: To evaluate the impact of COVID-19 pandemic on functional urology procedures in France. METHODS: A prospective study was conducted within 11 secondary and tertiary referral centers in France. Patients aged > 18 years who were diagnosed with a functional urology disease before the national lockdown (March 17th, 2020) and who required a surgery were included. Study period went from March 17th to September 30th 2020. The included interventions were listed according to the guidelines for functional urology enacted by the French Association of Urology and delay of reoperation was compared to the guidelines' delay. The primary outcome was the number of procedures left unscheduled at the end of the study period. Descriptive statistics were performed. RESULTS: From March 17th 2020 to September 3 rd 2020, 1246 patients with a previous diagnosis of a functional urological disease requiring a surgery were included. The mean follow-up was 140.4 days (± 53.4). Overall, 316 interventions (25.4%) were maintained whereas 74 (5.9%) were canceled, 848 (68.1%) postponed and 8 patients (0.6%) died. At the end of the follow-up, 184 patients (21.7%) were still not rescheduled. If the intervention was postponed, the mean delay between the initial and final date was 85.7 days (± 64.4). CONCLUSION: Overall, more than two thirds of interventions had to be postponed and the mean delay between the initial and final date was about three months.

Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters.

BACKGROUND: Neurogenic detrusor overactivity (NDO) is a severe pathological condition characterized by involuntary detrusor contractions leading to urine leakage. This condition is frequent after spinal cord injury (SCI). Gene therapy for NDO requires the development of vectors that express therapeutic transgenes driven by sensory neuron-specific promoters. The aim of this study was to develop and assess tools for the characterization of sensory neuron-specific promoters in dorsal root ganglia (DRG) neurons after transduction with herpes simplex virus type 1 (HSV-1)-based amplicon defective vectors. METHODS: The HSV-1 vector genome encoded two independent transcription cassettes: one expressed firefly luciferase (FLuc) driven by different promoters' candidates (rTRPV1, rASIC3, rCGRP, or hCGRP), and the other expressed a reporter gene driven by an invariable promoter. The strength and selectivity of promoters was assessed in organotypic cultures of explanted adult DRG, or sympathetic and parasympathetic ganglia from control and SCI rats. RESULTS: The rCGRP promoter induced selective expression in the DRG of normal rats. The rTRPV-1 promoter, which did not display selective activity in control rats, induced selective expression in DRG explanted from SCI rats. CONCLUSIONS: This study provides a methodology to assess sensory neuron-specific promoters, opening new perspectives for future gene therapy for NDO.

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.

Nocturia in patients with cognitive dysfunction: a systematic review of the literature.

BACKGROUND: The objective of this study is to evaluate current literature on the association between cognitive dysfunction and nocturia. METHODS: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was conducted through MEDLINE, EMBASE and COCHRANE databases and completed in November 2019. Randomized and non-randomized studies were included if they assessed the association between cognitive dysfunction and nocturia in older participants with or without neurological diseases. The quality of included studies was evaluated using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS). RESULTS: A total of 8 cross-sectional studies conducted in older patient populations met the criteria for inclusion. A statistically significant association was identified in 6 studies on univariate analysis, which persisted in 2 studies after controlling for confounding factors. The association between cognitive dysfunction and nocturia was positive for all 6 significant analyses. The overall risk of bias was unclear. CONCLUSION: A significant positive association between cognitive dysfunction and nocturia was identified. However, research has been limited to cross-sectional studies, which precludes identification of causality between cognitive dysfunction and nocturia. Heightened awareness of the complex interplay between cognition and nocturia would allow professionals involved in the care of cognitively impaired patients with concomitant nocturia to more effectively manage these symptoms.

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.

Development and Validation of a Questionnaire to Assess Barriers to Physical Activity After Stroke: The Barriers to Physical Activity After Stroke Scale.

OBJECTIVE: To develop and validate a self-reported questionnaire assessing the barriers to physical activity (PA) among stroke survivors. DESIGN: Psychometric study. SETTING: Ambulatory stroke care. PARTICIPANTS: A total of one hundred and forty-six (N=146) individuals were included in this study. In stage 1, community-living stroke survivors (n=37; 13 women) with low-moderate disability (modified Rankin Score 0-3, stroke >3mo) were included. In stage 2, participants (n=109; 40 women) with same characteristics were included. Nine professionals experienced in PA for poststroke patients formed an expert panel. INTERVENTIONS: In stage 1, semistructured interviews identified perceived barriers to PA, which were then selected by the expert panel and grouped on a Barriers to Physical Activity After Stroke (BAPAS) scale. In stage 2, stroke participants completed a personal information questionnaire and the BAPAS scale. MAIN OUTCOME MEASURES: An item selection process with factor analysis was carried out. The suitability of the data set was analyzed using the Kaiser-Meyer-Olkin coefficient, internal consistency was evaluated by Cronbach α, and concurrent validity was assessed with Spearman correlation coefficients between the BAPAS scale and the modified Rankin Scale. Test-retest repeatability was estimated using 2-way random effects intraclass correlation coefficient model 2,1 at 4-6 day follow-up (n=21). RESULTS: Factor analysis supported a 14-item BAPAS that explained 62% of total variance (Kaiser-Meyer-Olkin=0.82) and total score calculated higher than 70 (higher scores for higher barriers). Cronbach α was 0.86, Spearman correlation with the modified Rankin Scale was r=0.65 (P<.001), and test-retest intraclass correlation coefficient was 0.91 (95% CI, 0.79-0.97). The BAPAS scores were higher in patients with greater disabilities and in those with a longer time since the stroke event (P<.01). CONCLUSION: We developed and validated the BAPAS scale to assess barriers to PA in stroke survivors with low-moderate disability with promising psychometric properties.

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.

A study of the 200-metre fast walk test as a possible new assessment tool to predict maximal heart rate and define target heart rate for exercise training of coronary heart disease patients.

OBJECTIVE: To develop a new predictive model of maximal heart rate based on two walking tests at different speeds (comfortable and brisk walking) as an alternative to a cardiopulmonary exercise test during cardiac rehabilitation. DESIGN: Evaluation of a clinical assessment tool. SETTING: A Cardiac Rehabilitation Department in France. SUBJECTS: A total of 148 patients (133 men), mean age of 59 ±9 years, at the end of an outpatient cardiac rehabilitation programme. MAIN MEASURES: Patients successively performed a 6-minute walk test, a 200 m fast-walk test (200mFWT), and a cardiopulmonary exercise test, with measure of heart rate at the end of each test. An all-possible regression procedure was used to determine the best predictive regression models of maximal heart rate. The best model was compared with the Fox equation in term of predictive error of maximal heart rate using the paired t-test. RESULTS: Results of the two walking tests correlated significantly with maximal heart rate determined during the cardiopulmonary exercise test, whereas anthropometric parameters and resting heart rate did not. The simplified predictive model with the most acceptable mean error was: maximal heart rate = 130 - 0.6 × age + 0.3 × HR200mFWT (R(2) = 0.24). This model was superior to the Fox formula (R(2) = 0.138). The relationship between training target heart rate calculated from measured reserve heart rate and that established using this predictive model was statistically significant (r = 0.528, p < 10(-6)). CONCLUSIONS: A formula combining heart rate measured during a safe simple fast walk test and age is more efficient than an equation only including age to predict maximal heart rate and training target heart rate.

Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity-A Retrospective Analysis of Practice and Safety.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.

[Incidence of urinary tract infection after urodynamics among patients with neurogenic bladder]. / Incidence des infections urinaires post-cystomanométrie chez les patients présentant une vessie neurogène ­ évaluation des pratiques.

OBJECTIVE: The indication for prophylactic antibiotic therapy during cystomanometry to prevent urinary tract infection (UTI) has long been recommended. However, limited data support this approach. Our study aims to evaluate the incidence of UTIs following cystomanometry without prophylactic antibiotics in patients with neurogenic bladder. MATERIALS AND METHODS: This prospective, monocentric study was conducted from February 2023 to March 2023 at a specialized neuro-urology center, including all consecutive patients with lower urinary tract disorders of neurogenic origin referred for cystomanometry. The occurrence of UTIs following cystomanometry was assessed via telephone follow-up on day 14. RESULTS: A total of 100 patients were included, with a median age of 51years, with neurogenic bladder predominantly attributed to spinal cord injury (69/100). Ultimately, 11 patients reported UTIs within 14days post-cystomanometry, with only one being febrile, and none requiring hospitalization. No specific risk factors could be identified. CONCLUSION: According to our study, the incidence of UTIs following cystomanometry without prophylactic antibiotic therapy is 11%, which is equivalent to the incidence with antibiotic prophylaxis. These preliminary results support the lack of benefit of peri-cystomanometry antibiotic therapy.

Is it possible to individualize intensity of eccentric cycling exercise from perceived exertion on concentric test?

OBJECTIVE: To assess the safety and acute effects of a procedure using perceived exertion during a prior submaximal concentric (CON) test to individualize eccentric (ECC) cycling exercise intensity. DESIGN: Prospective, monocentric open study. SETTING: Technological investigation platform at a physical medicine and rehabilitation department in a university hospital. PARTICIPANTS: Healthy subjects (N=18; 15 men, 3 women) aged between 22 and 37 years. INTERVENTIONS: The subjects performed 3 cycling exercises: (1) incremental CON test to determine the comfortable pedaling power (CPP) corresponding to a Borg scale rating of 12 (rate of perceived exertion); (2) steady-state CON exercise at the CPP workload to determine the corresponding plantar pressure; and (3) steady-state ECC exercise with an imposed resistance corresponding to the CPP plantar pressure. MAIN OUTCOME MEASURES: Rate of perceived exertion on Borg scale, oxygen uptake (V˙o2), heart rate, cardiac output, and stroke volume using inert gas rebreathing techniques were measured during steady-state CON and ECC exercises. Muscle soreness was rated on a visual analog scale immediately, 24, and 48 hours after the tests. RESULTS: No adverse effects were reported. V˙o2 was about 5 times the resting value during CON exercise, while it was twice that during ECC exercise. Cardiac output was lower during ECC exercise (P<.05). This moderate increase of cardiac output was exclusively linked to a greater increase in stroke volume during ECC exercise than during CON exercise (P<.05). CONCLUSIONS: Moderate-intensity ECC cycling exercise tailored according to perceived exertion during a prior CON test is well tolerated. It corresponds to a limited muscular use of oxygen and to an isolated increase in stroke volume. It appears to be a feasible procedure for preconditioning before ECC training.

Safety and Effectiveness of Repeated Botulinum Toxin A Intracavernosal Injections in Men with Erectile Dysfunction Unresponsive to Approved Pharmacological Treatments: Real-World Observational Data.

Intracavernosal injections of botulinum toxin A (BTX/A ic) may be effective for difficult-to-treat erectile dysfunction (ED). This is a retrospective case series study of the effectiveness of repeated off-label BTX/A ic (onabotulinumtoxinA 100U, incobotulinumtoxinA 100U or abobotulinumtoxinA 500U) in men with ED and insufficient response to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandinE1 intracavernosal injections (PGE1 ICIs), defined as an International Index of Erectile Function-Erectile Function domain score (IIEF-EF) < 26 on treatment. Further injections were performed on patients' requests, and the files of men who underwent at least two injections were reviewed. The response to BTX/A ic was defined as the achievement of the minimally clinically important difference in IIEF-EF adjusted to the severity of ED on treatment at baseline. Out of 216 men treated with BTX/A ic and PDE5-Is or PGE1-ICIs, 92 (42.6%) requested at least a second injection. The median time since the preceding injection was 8.7 months. In total, 85, 44 and 23 men received, respectively, two, three and four BTX/A ic. The overall response rate was 77.5%: 85.7% in men with mild ED, 79% for moderate ED and 64.3% for severe ED on treatment. The response increased with repeated injections: 67.5%, 87.5% and 94.7%, respectively, after the second, third and fourth injections. Post-injection changes in IIEF-EF were similar across injections. The time from injection to request for a further injection varied little. Four men reported penile pain at the time of injection (1.5% of all injections), and one experienced a burn at the penile crus. Repeated BTX/A injections combined with PDE5-Is or PGE1-ICIs produced an effective and durable response, with acceptable safety.

Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin®) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series.

Registered pharmacological treatments are insufficiently effective for erectile dysfunction (ED) in around 30% of affected men. Intracavernosal injection (ICI) of ona- and abobotulinumtoxinA can reduce ED in insufficient responders. We aimed to assess the safety and effectiveness of incobotulinumtoxinA ICI as an add-on therapy to phosphodiesterase-type 5 inhibitors (PDE5-Is) or prostaglandinE1 ICIs (PGE1 ICIs) to treat ED that did not respond sufficiently to this treatment alone. We retrospectively analyzed data from 66 men with difficult to treat ED treated with single or repeated incobotulinumtoxinA 100U ICI as an add-on therapy. Response rate (increase in International Index of Erectile Function-Erectile Function domain score ≥ the minimum clinically important difference) was 52% (median (1st-3rd quartile) 43.5 (34-71) days post-incobotulinumtoxinA ICI). ED etiology (except spinal cord injury) and severity did not influence effectiveness. Only a clinically significant response to the 1st injection predicted a request for a 2nd injection (OR = 5.6, 95%, CI 1.6-19.4). Three men reported mild penile pain during the injection. These results provide preliminary evidence for the effectiveness and safety of incobotulinumtoxinA ICI as an add-on therapy to treat ED that is insufficiently responsive to standard care and provides support for the multicenter randomized clinical trial NCT05196308.

BoNT/A1 Secondary Failure for the Treatment of Neurogenic Detrusor Overactivity: An Ex Vivo Functional Study.

Management of neurogenic detrusor overactivity (NDO) remains a clinical priority to improve patients' quality of life and prevent dramatic urological complications. Intradetrusor injection of onabotulinumtoxinA (BoNT/A1, botulinum neurotoxin A1) is approved as second therapeutic line in these patients, demonstrating a good efficacy. However, a loss of its efficacy over time has been described, with no clear understanding of the underlying mechanisms. This paper aims at shedding new light on BoNT/A1 secondary failure in NDO through functional and structural analysis. Three groups of patients (either non-NDO, NDO with no toxin history or toxin secondary failure) were investigated using an ex vivo bladder strip assay. Detrusor strips were tensed in organ baths and submitted to electrical field stimulation to generate contractions. Recombinant BoNT/A1 was then added at various concentrations and contractions recorded for 4 h. Histology exploring BoNT/A1 targets, fibrosis and neuronal markers was also used. Detrusor strips from patients with BoNT/A1 secondary failure displayed a smaller sensitivity to toxin ex vivo at 3 nM compared to the other groups. Histological evaluation demonstrated the presence of cleaved Synaptosomal-Associated Protein, 25 kDa (c-SNAP25) in the detrusor from the toxin-secondary failure population, indicating some remaining in vivo sensitivity to BoNT/A1 despite the therapeutic escape. Moreover, residual c-SNAP25 did not affect parasympathetic-driven contractions observed ex vivo. This study confirms the slightly lower efficacy of BoNT/A1 in the BoNT/A1 secondary failure NDO group, suggesting that the escape from BoNT/A1 efficacy in NDO occurs at least at the parasympathetic level and could imply compensatory mechanisms for detrusor contraction.

Enteric Nervous System Remodeling in a Rat Model of Spinal Cord Injury: A Pilot Study.

The physiopathology of digestive disorders in patients with spinal cord injury (SCI) remains largely unknown, particularly the involvement of the enteric nervous system (ENS). We aimed in a rat model of chronic thoracic SCI to characterize (1) changes in the neurochemical coding of enteric neurons and their putative consequences upon neuromuscular response, and (2) the inflammatory response of the colon. Ex vivo motility of proximal and distal colon segments of SCI and control (CT) rats were studied in an organ chamber in response to electrical field stimulation (EFS) and bethanechol. Immunohistochemical analysis of proximal and distal segments was performed using antibodies again Hu, neuronal nitric oxide synthase, (nNOS), and choline acetyltransferase. Colonic content of acetylcholine and acetylcholinesterase was measured; messenger RNA (mRNA) expression of inflammatory cytokines was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) approaches. Compared with the CT rats, the contractile response to bethanechol was significantly decreased in the proximal colon of SCI rats but not in the distal colon. The proportion of nNOS immunoreactive (IR) neurons was significantly reduced in the proximal but not distal colon of SCI rats. No change in proportion of choline acetyltransferase (ChAT)-IR was reported; the tissue concentration of acetylcholine was significantly decreased in the proximal colon of SCI rats. The expression of tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) was significantly reduced in the proximal and distal colon of SCI rats. This study demonstrates that functional motor and enteric neuroplastic changes affect preferentially the proximal colon compared with the distal colon. The underlying mechanisms and factors responsible for these changes remain to be discovered.