An individual participant meta-analysis of mirabegron in multiple sclerosis and spinal cord injury.

INTRODUCTION: Our objective was to conduct an individual patient data meta-analysis (IPDMA) of the two published randomized placebo-controlled trials of mirabegron in people with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) or multiple sclerosis (MS). METHODS: We identified two randomized, placebo-controlled trials. We extracted individual patient data from the trials and evaluated two primary outcomes: change in maximum cystometric capacity and change in the patient perception of bladder condition (PPBC). We also evaluated several secondary outcomes related to urodynamic function and quality of life. We conducted three exploratory analyses to test hypotheses based on our clinical experiences with mirabegron in NLUTD. Analysis of covariance with adjustment for baseline values was used for the statistical analysis. RESULTS: Our IPDMA included 98 patients from the two trials. The results showed that mirabegron was associated with a significant improvement in maximum cystometric capacity (+41 mL, p = 0.04) and in the PPBC (-0.8, p < 0.01) compared to placebo. Secondary outcomes including peak neurogenic detrusor overactivity pressure (-20 cm H2O, p < 0.01), incontinence-QOL score (+12, p < 0.01), and 24 h pad weights (-79 g, p = 0.04) also improved significantly compared to placebo. Exploratory analyses found similar improvements in people with MS and SCI; some outcomes improved to a greater degree among people with incomplete SCI, or SCIs that were below T7. CONCLUSIONS: Our IPDMA provides evidence supporting the use of mirabegron in patients with NLUTD due to SCI or MS. Further work evaluating differential responses in people with different SCI lesion characteristics may be warranted.

Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Risk of genitourinary malignancy in patients that receive anticoagulant or antiplatelet therapy.

OBJECTIVES: Haematuria is a common indication for a urology evaluation. In many cases, its cause is not determined unequivocally, but it does not pose any threat to the patient. However, it can represent the first symptom of urinary tract cancer. BACKGROUND: The present study aimed to compare the risk of urological malignancies in patients with haematuria who received antiplatelet or anticoagulant therapy versus those who did not. METHODS: This prospective study included 562 patients with haematuria during the period of 2018‒2021. Among these, 129 patients had macroscopic haematuria. All patients underwent a urinary tract ultrasound, CT with urography, and cystoscopy. Patients with suspected malignancy underwent an appropriate surgical procedure with a pathology examination. Data were analysed with univariate and multiple logistic regression. RESULTS: The incidence rates of malignancies were 21.5 % overall, and 44.2 % and 14.8 % among patients with macroscopic and microscopic haematuria, respectively. Univariate regression showed that the odds of malignancy was significantly higher among patients with antiplatelet therapy compared to patients without antiplatelet therapy (OR: 1.88, 95% CI: 1.14‒3.05). In contrast, anticoagulation therapy did not significantly increase the odds of malignancy compared to no anticoagulation therapy (OR: 1.45, 95% CI: 0.74‒2.69). However, a multiple logistic regression model that included other known risk factors (e.g., sex or age) showed similar odds of malignancy among these patient groups. CONCLUSIONS: Malignancy risk for patients who received anticoagulant or antiplatelet therapy was similar to the risk observed in the general population. Antiplatelet and anticoagulant therapy were not significant risk factors of urological malignancy in patients with haematuria. The results from the present study will be used in a power analysis for an upcoming multicentre study (Tab. 4, Ref. 17). Text in PDF www.elis.sk Keywords: anticoagulation therapy, antiplatelet therapy, cancer, haematuria, risk factor.

Acquired haemophilia as a complicating factor in treatment of non-muscle invasive bladder cancer: A case report.

BACKGROUND: Acquired haemophilia (AH) is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII. In some patients, AH is associated with a concomitant malignancy. In case of surgical intervention, AH poses a high risk of life-threatening bleeding. CASE SUMMARY: A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection. A severe haematuria developed postoperatively warranting two endoscopic revisions; however, no clear source of bleeding was identified in the bladder. Subsequent haematological examination established a diagnosis of AH. Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately. The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery. At the 38-mo follow-up, both AH and bladder cancer remained in complete remission. CONCLUSION: AH is a rare, life-threatening haematological disease. AH should be considered in patients with persistent severe haematuria or other bleeding symptoms, especially if combined with isolated activated partial thromboplastin time prolongation.

Differences between brain responses to peroneal electrical transcutaneous neuromodulation and transcutaneous tibial nerve stimulation, two treatments for overactive bladder.

OBJECTIVES: To compare brain responses to peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) and transcutaneous tibial nerve stimulation (TTNS), two methods for treating overactive bladder (OAB), using functional magnetic resonance imaging (fMRI). The present study was not designed to compare their clinical efficacy. MATERIALS AND METHODS: This study included 32 healthy adult female volunteers (average age 38.3 years (range 22-73)). Brain MRI using 3 T scanner was performed during three 8-min blocks of alternating sequences. During each 8-min block, the protocol alternated between sham stimulation (30 s) and rest (30 s) for 8 repeats; then peroneal eTNM® stimulation (30 s) and rest (30 s) for 8 repeats; then, TTNS stimulation (30 s) and rest (30 s) for 8 repeats. Statistical analysis was performed at the individual level with a threshold of p = 0.05, family-wise error (FWE)-corrected. The resulting individual statistical maps were analyzed in group statistics using a one-sample t-test, p = 0.05 threshold, false discovery rate (FDR)-corrected. RESULTS: During peroneal eTNM®, TTNS, and sham stimulations, we recorded activation in the brainstem, bilateral posterior insula, bilateral precentral gyrus, bilateral postcentral gyrus, left transverse temporal gyrus, and right supramarginal gyrus. During both peroneal eTNM® and TTNS stimulations, but not sham stimulations, we recorded activation in the left cerebellum, right transverse temporal gyrus, right middle frontal gyrus, and right inferior frontal gyrus. Exclusively during peroneal eTNM® stimulation, we observed activation in the right cerebellum, right thalamus, bilateral basal ganglia, bilateral cingulate gyrus, right anterior insula, right central operculum, bilateral supplementary motor cortex, bilateral superior temporal gyrus, and left inferior frontal gyrus. CONCLUSIONS: Peroneal eTNM®, but not TTNS, induces the activation of brain structures that were previously implicated in neural control of the of bladder filling and play an important role in the ability to cope with urgency. The therapeutic effect of peroneal eTNM® could be exerted, at least in part, at the supraspinal level of neural control.

Effect duration of the initial course of peroneal electrical Transcutaneous NeuroModulation in patients with overactive bladder.

PURPOSE: The aim of this prospective 12-month follow-up study is to evaluate the persistence of the treatment effect achieved during the initial course of peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) in patients with overactive bladder (OAB). METHODS: This study enrolled 21 female patients who participated in two previous clinical studies designed to assess the efficacy and safety of peroneal eTNM®. The patients were left without subsequent OAB treatment and were invited to attend regular follow-up visits every 3 months. The patient's request for additional treatment was considered an indicator of the withdrawal of the treatment effect of the initial course of peroneal eTNM®. The primary objective was the proportion of patients with persisting treatment effect at follow-up visit 12 months after initial course of peroneal eTNM®. Descriptive statistics are presented using median, correlation analyses were computed using a nonparametric Spearman correlation. RESULTS: The proportion of patients with persistent therapeutic effect of the initial course of peroneal eTNM® was 76%, 76%, 62% and 48% at 3, 6, 9 and 12 months, respectively. There was a significant correlation between patient reported outcomes and the number of severe urgency episodes with or without urgency incontinence as reported by patients at each follow-up visit (p = 0.0017). CONCLUSION: The treatment effect achieved during the initial phase of peroneal eTNM® persists for at least 12 months in 48% of patients. It is likely that the duration of effects is dependent on the length of the initial therapy.

Permanent urethral catheter - a good servant, but bad master: Guidelines for prevention, diagnosis, and treatment of catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTI) are among the most common healthcare-associated infections, which increase morbidity, mortality, prolong the length of hospitalization and have a significant impact on the cost of treatment. The most efficient preventive method is removing catheters as soon as possible and avoid unnecessary catheterizations. Treatment of asymptomatic bacteriuria is not recommended. In cases of serious CAUTI, vigorous antibiotic therapy covering multidrug-resistant uropathogens should be initiated. These recommendations are intended for all medical specialties to improve the care of patients with indwelling catheters in the prevention, diagnosis, and treatment of CAUTI in primary care and subsequent long-term care.

Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?

AIMS: Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. METHODS: 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. RESULTS: Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI-RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). CONCLUSIONS: We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.

Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder.

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

Peroneal electrical transcutaneous neuromodulation in the home treatment of the refractory overactive bladder.

INTRODUCTION AND HYPOTHESIS: The aim of this prospective, open-label, multicenter, noncomparative study was to evaluate the efficacy and safety of peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) using the URIS® neuromodulation system as a home treatment for refractory overactive bladder (OAB). METHODS: The patients were treated with daily peroneal eTNM® for 30 min over a 6-week period. The primary endpoint was defined as the proportion of responders, i.e., participants with ≥ 50% reduction in the average daily sum of severe urgency episodes (defined as "I could not postpone voiding but had to rush to the toilet in order not to wet myself") and urgency incontinence episodes. In addition, bladder diary variables, symptom severity (OAB V8 questionnaire), treatment satisfaction (visual analog scale), and pain perception (visual analog scale) were evaluated at baseline (BL), at week 4 (W4), and at the end of treatment (EoT). Safety evaluations included monitoring of the incidence and severity of adverse events (AEs). Changes in time were analyzed using the nonparametric one-way ANOVA Friedman test for categorical variables and the Wilcoxon rank-sum test for the noncategorical variables. RESULTS: In total, 40 subjects were screened and 29 were included in the full analysis set. The proportion of responders was 86% at W4 and 79% at EoT. There was a significant reduction in frequency (p<0.001), number of severe urgency episodes (p< 0.001), number of urgency incontinence episodes (p=0.001), and number of nocturia episodes (p=0.002). There was a significant improvement in the OAB V8 score and treatment satisfaction (both p<0.001). Two mild treatment-related AEs were recorded. Both patients recovered without sequelae and completed the study. CONCLUSIONS: Peroneal eTNM® proved to be a highly effective and safe method for the home treatment of OAB, providing a therapeutic response in approximately 80% of patients.

Clinical Utility of ß3-Adrenoreceptor Agonists for the Treatment of Overactive Bladder: A Review of the Evidence and Current Recommendations.

This nonsystematic review provides a summary of current evidence on the use of ß3-adrenoreceptor agonists (ß3-ARAs) for the treatment for lower urinary tract symptoms. Soon after their discovery in 1989, ß3-ARs were identified as a predominant adrenoreceptor subtype in the human urinary bladder. Although it is widely believed that ß3-ARAs cause detrusor relaxation, the effect on bladder afferent signaling likely plays an important role in their mechanism of action as well. In 2011 and 2012, mirabegron was approved for clinical use in overactive bladder (OAB) patients. Pooled analysis of data from prospective randomized studies on >60,000 OAB patients showed that when compared to placebo, mirabegron was superior with respect to reducing the frequency, number, and severity of urgency episodes, number of incontinence episodes and increasing dry rate, but not in reduction of nocturia episodes. The only side effect showing significantly higher incidence than placebo was nasopharyngitis. Mirabegron is approved for OAB treatment in all age-groups and in pediatric patients with neurogenic bladder. Vibegron is another ß3-ARA approved for OAB treatment in the US and Japan. Several large, multicenter, double-blind, randomized trials have documented statistically significant superiority of vibegron over placebo on all efficacy end points. Other ß3-ARAs are being developed; however, to date none has been introduced to clinical use. All ß3-ARAs provide efficacy similar to anticholinergics. They have a favorable safety profile and are well tolerated. Due to their different mechanisms of action, combination of ß3-ARAs with anticholinergic compounds allows for increased efficacy.

Peroneal Electrical Transcutaneous NeuroModulation as a New Treatment for Patients with Overactive Bladder: An Initial Clinical Experience.

INTRODUCTION: The aim of this study was to determine whether peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) using the URIS® neuromodulation system can be used in individuals with refractory overactive bladder (OAB). METHODS: Eighteen female patients with idiopathic OAB who failed previous behavioral and pharmacological therapy were enrolled. Patients were treated with the URIS® neuromodulation system using active electrodes placed on the popliteal fossa, targeting the peroneal nerve for 30 min once a week for 12 weeks. Changes in OAB symptoms and patient-reported outcomes from baseline to the end of the study were analyzed. A nonparametric Wilcoxon signed-rank test was used to assess changes in variables. Statistical significance was defined as p ≤ 0.05. RESULTS: We observed a significant reduction in micturition frequency (p = 0.022), number of severe urgency episodes (p < 0.001), urgency incontinence episodes (p = 0.001), and nocturia episodes (p = 0.027). A decrease in Patient Perception of Bladder Condition score (p < 0.001) was also observed. Posttreatment, 15 patients (83.3%) reported a moderate or significant reduction in their bladder bother. Throughout the study, two adverse events were recorded with no causal relationship to the study treatment. DISCUSSION/CONCLUSIONS: Our study documented a significant reduction in all OAB symptoms and an improvement in all patient-reported outcomes in patients treated with peroneal eTNM® using the URIS® neuromodulation system.

Peroneal Electric Transcutaneous NeuroModulation (eTNM®): A Novel Method for the Treatment of the Overactive Bladder.

Overactive bladder syndrome (OAB) is a prevalent medical problem with a significant impact on the quality of life of the affected individuals. Pharmacotherapy is considered the main treatment method, although it is discontinued in a significant proportion of patients due to inefficacy or associated side effects. If pharmacotherapy fails, patients can undergo peripheral neuromodulation of the somatic nerves of the lower limb or sacral neuromodulation; however, neither of these represents an ideal therapeutic tool. The Peroneal electric Transcutaneous NeuroModulation (Peroneal eTNM®), based on the selective stimulation of the peroneal nerve, is the new fully noninvasive neuromodulation method intended to treat OAB. The URIS® neuromodulation system, engineered to provide Peroneal eTNM®, consists of the URIS® device, URIS® active electrodes, and the biofeedback foot sensor (BFS). The unique design of the URIS® device and URIS® active electrodes allows for the use of a low voltage and current during neuromodulation, which significantly reduces the unpleasant sensations. The BFS allows for precise localization of the active electrodes and for continuous adjustment of the voltage and frequency to achieve the optimal therapeutic effect. The URIS® system adopts several principles of telemedicine, which makes it compatible with the US Food and Drug Administration (FDA) and European Union (EU) regulations for home-based use. This article describes both the Peroneal eTNM® method and the URIS® neuromodulation system, including its technical specifications and data from laboratory testing. Preclinical and early clinical data demonstrate the feasibility of this new method for noninvasive OAB treatment and possible implications for clinical practice.

The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model - A Protocol for a Randomized, Controlled, Blinded Trial in Pigs.

BACKGROUND: Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension. METHODS AND ANALYSIS: In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing. ETHICS AND DISSEMINATION: The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences. HIGHLIGHTS: The optimal management of long-gap esophageal atresia remains controversialPrimary anastomosis could improve functional outcomes and reduce complicationsBotulinum Toxin Type A decreases tissue tension and could facilitate anastomosisReduced tension could further abate the risk for anastomotic stricture and leakageWe present a model to evaluate the method in long- and short-gap esophageal atresia.

Cardiovascular safety of mirabegron in individuals treated for spinal cord injury- or multiple sclerosis-induced neurogenic detrusor overactivity.

PURPOSE: To analyze cardiovascular safety of mirabegron in patients with spinal cord injury (SCI)- and multiple sclerosis (MS)-induced neurogenic detrusor overactivity (NDO) in a prospective, randomized, double-blind, placebo-controlled study. METHODS: Seventy-eight patients were enrolled into the study, and 66 of them were included into the final analysis. In 49 (74.2%), NDO developed due to suprasacral SCI, 17 (25.8%) suffered from NDO due to MS. Eleven patients were previously treated for hypertension and one for arrhythmia. All study participants received placebo for 2 weeks run-in period. Subsequently, eligible subjects were randomized for 4 weeks of active treatment with mirabegron 50 mg once daily (Group A; n = 32) or placebo (Group B; n = 34). Data from resting electrocardiography (ECG), 24-h ECG and blood pressure monitoring, and echocardiographic examination, were used for cardiovascular safety assessment. All reported variables were evaluated at time of randomization and at the end of the study. Longitudinal changes of variables within the groups and differences between the groups were assessed using nonparametric Kruskal-Wallis test, and p ≤ 0.05 was considered statistically significant. RESULTS: No statistically significant longitudinal changes were found in safety variables, except for prolongation of QT interval in placebo group (p = 0.0328) recorded by resting ECG. No significant difference between the Groups A and B, in any of the variables, was observed. A single cardiovascular study drug-related adverse event was recorded in a patient with cervical SCI (3.13%). CONCLUSIONS: Our results suggest that mirabegron can be safely used in the treatment of patients with SCI- and MS-induced NDO.

Intravesical Loss of OnabotulinumtoxinA During Endoscopic Intradetrusor Injection - A Multicenter Experience.

PURPOSE: To evaluate intravesical loss of onabolunumtoxinA (onaBTA) during endoscopic injection into the bladder wall for treatment of neurogenic detrusor overactivity (NDO). The intraluminal loss of onaBTA cannot be determined directly, therefore we added methylene blue (MB) to reconstitute onaBTA. Subsequently we used spectrophotometry to determine the total amount of MB in the irrigation fluid, which allowed us to calculate total intraluminal loss of onaBTA. METHODS: The study population was consisted of 48 patients with NDO. The mean age was 36.6±8.9 years. Forty-two patients suffered from NDO due to spinal cord injury and 6 patients suffered from multiple sclerosis. Each patient received 200 units of onaBTA administered by 30 endoscopic injections (1 mL per injection) using a 23-G needle. The entire volume of irrigation fluid was collected and spectrophotometry was used to determine the MB concentration. The total amount of injected onaBTA, total amount of irrigation solution and the known amount of MB used during reconstitution, allowed for the determination of intravesical loss of onaBTA. RESULTS: Forty-five patients were included in the final analysis. The mean volume of irrigation fluid was 603.33±400.14 mL. The mean absorbance was 0.14±0.12 with the mean MB concentration 0.19±0.18 mg/L. The mean calculated loss of onaBTA was 4.14±4.11 units. CONCLUSION: The endoscopic injection of onaBTA marked by MB into the bladder wall is associated with minimal intravesical loss of the agent, representing less than 3% of the administered dose of MB. This may reflect the amount of the onaBTA detected in the irrigation fluid.

One-year follow-up after urethroplasty, with the focus on both lower urinary tract and erectile function.

Background: Urethral stricture disease (USD) represents a complex urological problem. Urethroplasty is considered the gold standard for the treatment of USD. Most available studies report outcome data obtained from retrograde urethrography and uroflowmetry. Only a limited number of papers describe the effect of urethroplasty on erectile function and their results are inconsistent. The goal of this prospective study was to evaluate the effect of urethroplasty on both lower urinary tract and erectile function using objective parameters and standardized patient-reported outcome measurement tools.Materials and Methods: A total of 55 consecutive patients with USD were enrolled into the study. Patients underwent ventral onlay urethroplasty, urethroplasty according to the Asopa technique, dorsal onlay urethroplasty, cutaneous flap urethroplasty using the Orandi technique or anastomotic repair. All patients were evaluated using uroflowmetry, urethrography, the PROM-USS questionnaire and the International Index of Erectile Function-5 questionnaire (IIEF-5) pre-operatively and consequently post-op, in 3-month intervals. This study presents the comparison of baseline pre-op parameters and parameters 12 months after the surgery using the Wilcoxon signed rank test, Wilcoxon rank sum test and the Kruskal-Wallis one-way analysis of variance.Results: A significant improvement in uroflowmetry parameters, all domains of the PROM-USS questionnaire, as well as the overall score of the IIEF-5 was observed. No statistically significant differences between sub-groups were found when comparing treatment results in patients with short versus long strictures and patients with penile urethra stricture versus bulbar or membranous urethra stricture.Conclusions: Urethroplasty yielded very good functional results with respect to both lower urinary tract and erectile functions.

Alpha-blockers for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta-analysis. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: We aimed to systematically assess the evidence on the efficacy and safety of alpha-blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha-blockers for the treatment of NLUTD in patients with MS. RESULTS: After screening of 7'015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo-controlled, single-blind trial and two prospective cohort studies. Alpha-blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha-blocker treatment was 3.89 (95% confidence interval 2.7-7.0). The general safety profile of alpha-blockers was favorable with 8% of the patients reporting adverse events. CONCLUSIONS: Alpha-blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted.

Effect of severity of urinary incontinence on quality of life in women.

AIMS: While the effect of different types of incontinence on the quality of life (QoL) has been clearly documented, the information about the impact of incontinence severity on QoL in women is lacking. Therefore, we investigated whether increasingly severe degrees of incontinence were linearly correlated with poorer QoL. METHODS: We included 391 incontinent women and 81 continent volunteers in the study and assessed them in accordance with routine clinical practice. A 24 h pad-weight test was used to objectively quantify the incontinence severity. We then stratified participants according to incontinence type and severity and assessed correlations between incontinence severity and Patient Perception of Bladder Condition (PPBC), International Consultation on Incontinence short-form questionnaire (ICIQ-SF), and King's Health Questionnaire (KHQ) quality of life scores in the entire study population and in individual groups according to incontinence type. RESULTS: Minimal incontinence was associated with significant negative impact on QoL, as measured by all quality of life assement tools. There were nonlinear correlations between scores on individual questionnaires and daily leakage volumes. Stress urinary incontinence had a weaker impact on quality of life than urge or mixed incontinence, as measured by PPBC (P < 0.0001), KHQ part 1 (P < 0.0001), and KHQ part 2 (P < 0.001). Stress urinary incontinence also had a weaker impact on QoL than mixed incontinence as measured by ICI-Q (P = 0.007). CONCLUSIONS: This study demonstrated that even mild urinary leakage significantly reduces the QoL, while subsequent increase in the degree of incontinence has only minimal additional effect. There was no linear correlation between incontinence severity and QoL.

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-Prospective, randomized, double-blind, placebo-controlled study.

AIMS: To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant. RESULTS: In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%. CONCLUSIONS: Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well.