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.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Transcutaneous tibial nerve stimulation in patients with multiple sclerosis and overactive bladder: a real-life clinical and urodynamic assessment.

AIMS: The aims of the present study were to assess the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on overactive bladder (OAB) symptoms and on urodynamic parameters in patients with multiple sclerosis (PwMS) and to seek predictive factors of satisfaction. METHODS: All PwMS who performed 12-24 weeks of TTNS and who underwent urodynamic assessment before and after treatment between June 2020 and October 2022 were included retrospectively. Data collected were bladder diaries, symptoms assessed with Urinary Symptoms Profile (USP), and urodynamic parameters (bladder sensations, detrusor overactivity, and voiding phase). Patients with improvement rated as very good or good on Patient Global Impression of Improvement (PGI-I) score were considered as responders. RESULTS: Eighty-two patients were included (mean age: 47.1 ± 11.5 years, 67 (82%) were women). The mean USP OAB sub-score decreased from 7.7 ± 3.5 to 6.0 ± 3.4 (p < 0.0001). On bladder diaries, voided volumes, void frequency, and the proportion of micturition done at urgent need to void significantly improved with TTNS (p < 0.05). No significant change was found in urodynamic parameters. According to the PGI-I, 34 (42.5%) patients were good responders. The only parameter associated with higher satisfaction was the percentage of micturition done at urgent need to void before the initiation of the treatment (39.8% ± 30.5 in the responder group vs 25.1% ± 25.6 in the low/no responder group; p = 0.04). CONCLUSION: TTNS improves OAB symptoms in PwMS, without significant changes on urodynamics. A high rate of strong or urgent need to void in daily life was associated with higher satisfaction.

De-obstruction of bladder outlet in humans reverses organ remodelling by normalizing the expression of key transcription factors.

BACKGROUND: Benign prostatic hyperplasia in elderly males often causes bladder outlet obstruction termed benign prostatic obstruction (BPO). BPO induces lower urinary tract symptoms and quantifiable urodynamic alterations in bladder function. When conservative medical treatments are exhausted, surgical interventions like transurethral resection of the prostate (TURP) are employed for bladder outlet de-obstruction. Elucidating the molecular changes in the human bladder resulting from BPO and their reversal post-de-obstruction is pivotal for defining the "point of no return", when the organ deterioration becomes irreversible. In this study we carried out a comprehensive molecular and urodynamic characterization of the bladders in men with BPO before TURP and 3 months after the relief of obstruction. METHODS: We report integrated transcriptome and proteome analysis of bladder samples from male patients with BPO before and 3 months after de-obstruction surgery (TURP). mRNA and protein profiles were correlated with urodynamic findings, specifically voiding detrusor pressure (PdetQmax) before TURP. We delineated the molecular classifiers of each group, pointing at the different pre-TURP bladder status. RESULTS: Age-matched patients with BPO without DO were divided into two groups based on the PdetQmax values recorded by UDI before de-obstruction: high and medium pressure (HP and MP) groups. Three months after de-obstruction surgery, the voiding parameters PdetQmax, Qmax and RV were significantly improved in both groups, without notable inter-group differences in the values after TURP. Patients with high PdetQmax showed less advanced remodeling and inflammatory changes than those with lower values. We detected significant dysregulation of gene expression, which was at least partially reversed by de-obstruction in both patients' groups. Transcription factor SOX21 and its target thrombospondin 4 (THBS4) demonstrated normalization post-TURP. CONCLUSIONS: Our findings reveal substantial yet incomplete reversal of cell signalling pathways three months after TURP, consistent with improved urodynamic parameters. We propose a set of biomarker genes, indicative of BPO, and possibly contributing to the bladder changes. This study unveils the stages of progressive obstruction-induced bladder decompensation and offers insights into selecting an optimal intervention point to mitigate loss of contractility.

Urinary biomarkers in children with neurogenic and non-neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

AIM: The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program. RESULTS: A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges's g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001). CONCLUSION: Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD.

Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.

AIMS: GDNF plays a crucial role in the stimulation of recovery, neuroplasticity and synaptic reorganization after spinal cord injury providing neuroprotection and neuroregeneration. Plasma GDNF levels are upregulated in cases of spina bifida owing to the intrauterine damage of the exposed spinal cord. Our aim was to compare the plasma GDNF levels in patients of spina bifida with non-spina bifida cases and assess the correlation with neurological impairment at one year of follow up. METHODS: Single centre prospective analysis of cases of spina bifida from 2020 to 2022 at presentation and after one year of follow up post-surgery. Cases with hernia and hydrocele without any other disorders were recruited into the control group. Plasma GDNF levels were assessed with immunoassay kits and compared with neurological involvement. RESULTS: 85 cases were included in the study. GDNF levels were elevated in cases compared to controls (mean 6.62 vs 1.76) with significant p value (<0.01). Same was observed for open and closed defects (mean 7.63 vs 4.86: p < 0.01). At follow up of 52 cases post-surgery cases with neurogenic bladder with abnormal urodynamic studies, sphincter involvement and motor impairment had significantly elevated baseline levels of GDNF compared with those who did not have this neurological impairment (p < 0.01). DISCUSSION: The neurotrophic factor up-regulation can reflect an endogenous attempt at neuroprotection against the biochemical and molecular cascades triggered by the spinal cord damage. This upregulation can be represented as important biochemical markers of severe spinal cord damage and can be associated with severity of spine injury in MMC patients. Our results are in keeping with these findings, that, there were increased levels of plasma GDNF levels in cases of spinal dysraphism compared to control population. Also, the type of lesion reflecting the severity whether a closed or an open dysraphism, showed significant difference in levels between them suggesting, yet again, more damage in open defect as expected. The levels were higher with involvement of bladder, sphincter and lower limb power. CONCLUSION: There is significant elevation of plasma GDNF levels in cases of spina bifida and this elevation is proportional to the degree of spinal damage and hence the neurological impairment. GDNF levels are a good predictor for assessing the severity of the lesion and thus the outcome in these cases. Additional prospective and long-term studies with a larger cohort are needed for a better understanding of neurotrophin pattern modulation in MMC.

Efficacy and safety of the implantable, magnetic resonance imaging-compatible StimRouter neuromodulation system in the treatment of refractory lower urinary tract symptoms in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS) significantly affect quality of life (QoL) of multiple sclerosis (MS) patients, and pharmacotherapy has limited efficacy. We investigated efficacy and safety of the implantable StimRouter neuromodulation system for treating refractory LUTS in MS. METHODS: This prospective, single-center, clinical trial was conducted at the Multiple Sclerosis Center of Lugano, Switzerland, involving MS patients treated with self-administered percutaneous tibial nerve stimulation delivered by StimRouter over 24 weeks. Changes in video-urodynamic parameters as well as LUTS severity were measured by Overactive Bladder Questionnaire (OAB-q), QoL using the Multiple Sclerosis Quality of Life (MSQoL-54), and treatment satisfaction using a 1-10 visual analogue scale. Adverse events were also recorded. RESULTS: Of 23 MS patients recruited, six had neurogenic detrusor overactivity (NDO), five had detrusor sphincter dyssynergia (DSD), and 12 had both NDO and DSD. Of patients with NDO, median bladder volume at first uninhibited contraction significantly increased from baseline to week 24 (median = 136 mL, interquartile range [IQR] = 101-244 mL vs. 343 mL, IQR = 237-391 mL; ß = 138.2, p = 0.001). No significant changes of urodynamic parameters were found in patients with DSD. OAB-q symptom scores progressively decreased, and OAB-q quality of life scores increased (ß = -0.50, p < 0.001 and ß = 0.47, p < 0.001, respectively), whereas MSQoL-54 scores did not significantly change (ß = 0.24, p = 0.084) in the overall population. Treatment satisfaction was overall high (median = 8, IQR = 6-9). No serious adverse events were recorded. CONCLUSIONS: StimRouter represents a minimally invasive, magnetic resonance imaging-compatible, self-administered neuromodulation device leading to objective and subjective improvements of OAB symptoms and related QoL in MS patients with refractory LUTS.

Beneficial carry-over effects of chronic at-home genital nerve stimulation on incontinence in individuals with spinal cord injury: A pragmatic trial.

BACKGROUND: Genital nerve stimulation (GNS) is a promising, but under-researched, alternative treatment for neurogenic detrusor overactivity (NDO) in those with spinal cord injury (SCI). OBJECTIVES: To investigate the urodynamic, quality-of-life (QOL) and carry-over effects of GNS when applied at home for 2 weeks by participants with incomplete SCI and NDO during activities of daily living. METHODS: Seven men and 1 woman participated in this 1-month protocol study. Urodynamic and QOL data were gathered during week 1 (baseline measurements), followed by 2 weeks of daily GNS at home using a portable device. GNS was applied either on-demand or thrice daily, depending on the individual's sensation. At week 4, post-stimulation tests were repeated to record any carry-over effect from the GNS. Participants maintained voiding diaries throughout the study. Assessments were carried out at the end of each protocol period in a randomized order. Clinical procedures were conducted at Taipei Medical University Hospital (Taipei, Taiwan). RESULTS: Everyone completed the study but only 7 of the 8 participants completed their voiding diary. Two weeks after GNS, average cystometric bladder capacity was increased by 30 % compared to baseline (P< 0.05). A 1-week carry-over effect was demonstrated as this capacity remained, on average, 35 % greater than baseline in week 4 after GNS was stopped (P< 0.05). Incontinence frequency significantly decreased by the end of week 3 (P< 0.05) but no significant improvements were recorded for either detrusor pressure or bladder compliance. CONCLUSIONS: Chronic at-home GNS improved cystometric bladder capacity and reduced urinary incontinence for individuals with incomplete SCI and NDO. A carry-over effect of 1 week was observed following GNS treatment. The use of portable GNS treatment that can be applied by the individual at home merits further investigation as alternative treatment for NDO in those with SCI.

Impact of deep resection of endometriosis in the pelvis on urodynamic parameters.

PURPOSE: To evaluate the effects of deep resection of endometriosis in the posterior pelvic region on urodynamic parameters. METHODS: A prospective observational study conducted with female patients diagnosed with deep pelvic endometriosis before and after endometriosis resection surgery. Clinical history, image exams, the Female Lower Urinary Tract Symptoms questionnaire, urodynamic examination, cystometry, and voiding study were evaluated. RESULTS: Patients aged 30-39 years old, operative duration of 132.5 minutes, and 2.7 days of hospital stay. Uroflowmetry and cystometry showed tendency for an increase after the surgery in the flow duration, time to maximum flow, and first voiding desire and decreased residual volume and maximum cystometric capacity. Opening, maximum urinary flow, and maximum flow pressure decreased at T1, and the closing parameters increased, although statistically non significant. The variables decreased at T1 in the urodynamic, except for detrusor overactivity. Although we observed a reasonable number of low bladder compliance and abnormal bladder sensation, the results were maintained at T1. General scores for filling and incontinence showed a significant decrease after surgery. CONCLUSIONS: A significant response in the patient's perception of urinary function was demonstrated after surgery. It is observed that the surgical procedure did not affect the uroflowmetric and cystometric characteristics of the evaluated patients.

Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives.

Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as "a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span". Despite the widespread prevalence of UAB/DU, there are significant gaps in our understanding of its pathophysiological mechanisms, diagnosis, and treatment compared with overactive bladder (OAB) and detrusor overactivity (DO). These gaps are such that clinicians regard UAB/DU as an incurable condition. In recent years, the understanding of UAB has increased. The definition of UAB has been clarified, and the diagnostic criteria for DU have been considered more comprehensively. Meanwhile, a number of non-invasive diagnostic methods have also been reported. Clinical trials involving novel drugs, electrical stimulation, and stem cell therapy have shown promising results. Therefore, this review summarizes recent reports on UAB and DU and highlights the latest advances in their diagnosis and treatment.

Efficacy of single and repeated transurethral bladder neck incisions for female voiding dysfunction.

OBJECTIVE: This study aimed to assess the efficacy of single and repeat transurethral bladder neck incision (TUI-BN) for female voiding dysfunction caused by bladder outlet obstruction (BNO). Further, the predictive factors associated with better treatment outcomes were identified. METHODS: Women with voiding difficulty due to BNO who underwent TUI-BN were included in this research. All patients underwent videourodynamics study at baseline and after TUI-BN. Successful outcome was defined as a voiding efficiency of ≥ 66.7% and a global response assessment score of ≥ 2 after treatment. Repeat TUI-BN was considered for patients with insufficient improvement. The outcomes of repeat surgery, surgical complications, and predictive factors of successful outcomes were evaluated. RESULTS: In total 158 cases, the success rates were 61.4% and 45.2% after the first and second TUI-BN, respectively, with an overall cumulative rate of 70.3%. The success rates were comparable between patients with detrusor underactivity (DU) and those without (54.9% vs. 68.4%). The absence of a previous history of suburethral sling and a high baseline corrected maximum flow rate were a significant predictor of favorable outcomes. The cumulative rate of regaining self-voiding function was 95.1%. The incidence rates of vesico-vaginal fistula and de novo stress urinary incontinence requiring surgery were 1.2% and 2.5%, respectively. CONCLUSIONS: Regardless of the presence of DU, TUI-BN is effective against female voiding dysfunction caused by BNO. Repeat procedures are beneficial and can improve self-voiding function. A high corrected maximum flow rate and the absence of a previous history of suburethral sling can contribute to greater success rates.

Urologic manifestations of hypotonia, ataxia, and delayed development syndrome (HADDS), a rare neurodevelopmental disorder.

INTRODUCTION: Early B-cell factor 3 (EBF3) is a transcription factor involved in neuronal differentiation and maturation. Pathogenic variants are associated with hypotonia, ataxia, and delayed development syndrome (HADDS) (MIM#617330). Urologic manifestations are common and may have implications regarding long term renal function. OBJECTIVE: To review all known patients with pathogenic variants of the EBF3 gene resulting in HADDS with urologic manifestations. We hypothesize a high rate of bladder dysfunction secondary to the EBF3 variant's impact on relaxation of the urinary sphincter leading to detrusor sphincter dyssynergia (DSD). METHODS: The PubMed database was queried for publications of the EBF3 mutation between January 2017 and January 2023. Search terms were "EBF3 mutation OR HADDS AND urology OR phenotype". Retrospective analysis of HADDS patients cared for in our institution was performed. Demographic and clinical information was collected. RESULTS: We identified 52 patients (33F:19M) through literature (28F:18M) and retrospective review (5F:1M). There was a high prevalence of genitourinary physical exam abnormalities, history of urinary tract infection, vesicoureteral reflux (VUR), and diagnosis of neurogenic bladder. Within the literature review cohort, 67% had a urologic diagnosis. Females were disproportionately affected with urologic manifestations. In our cohort, four of six children were diagnosed with VUR and severe voiding dysfunction consistent with neurogenic bladder (67%). These children were managed with a vesicostomy. Five children had bowel dysfunction requiring therapy. Urodynamics suggested a high prevalence of external sphincter dyssynergia. Less severe forms of DSD were felt to be implicated in the abnormal voiding parameters in children who presented later in life based on non-invasive flow studies. DISCUSSION: There is significant variability in the phenotypic presentation of patients with HADDS. While EBF3 plays a clear role in neurodevelopment, it also impacts muscle development and may impact muscle relaxation. The location of the genetic variant may impact the degree of DSD, with more severe forms leading to earlier presentations. Initial work-up should include a renal ultrasound (RUS) and post void residual (PVR). Consideration can be given to obtaining a VCUG, DMSA scan or urodynamic studies. Yearly screening should be pursued with an RUS and PVR in those with an initial unremarkable work-up given the variable timing and severity of presentation. CONCLUSION: Urologic manifestations of HADDS include high rates of bladder dysfunction secondary to DSD, vesicoureteral reflux, urinary tract infection, and cryptorchidism. These patients are at risk of renal deterioration if urinary abnormalities are not properly diagnosed and managed.

The assessment and management of voiding dysfunction in adults living with cerebral palsy.

PURPOSE: Improvements in life expectancy have resulted in an increasing number of adults with cerebral palsy, of which over a third will have neurogenic lower urinary tract dysfunction (NLUTD). This review explores urinary dysfunction in adults with cerebral palsy. METHODS: Relevant literature on NLUTD in adults with cerebral palsy was identified using an unrestricted search of PubMed. RESULTS: Urinary incontinence is the most common complaint, often accompanied by frequency and urgency. Special consideration should be given to women and in those with worse motor or cognitive dysfunction as they have been shown to have more severe urologic symptoms. NLUTD can have significant morbidity and impact quality of life. Hospital admission, urinary tract infections, and hydronephrosis are common urologic complications, with poor urinary function associated with decreased quality of life (QOL). Neurogenic detrusor overactivity is the most common urodynamic abnormality, with elevated detrusor leak point pressure and reduced bladder capacity. Detrusor sphincter dyssynergy is present in some patients and maybe secondary to generalized spasticity or incomplete upper motor neuron injury. Elevated bladder capacity is also present in a portion of patients, and becomes particularly relevant in adults as a result of increased spasticity of the urinary sphincter. Conservative management like functional toileting strategies, medications, and incontinence aids are successful in most patients. Medical management with anticholinergics is well described, and frequently the only intervention required, particularly in children. Intermittent clean catheterization has mixed results with this population, as its efficacy is limited by pelvic spasticity and patient factors. Surgical intervention, while often successful, should be restricted to select patients, as it is associated with significant morbidity in this population. CONCLUSION: Management of NLUTD in adults with CP involves conservative management, medications, and in rare cases surgical intervention.

[Efficacy of fesoterodine for prevention of autonomic dysreflexia in patients with neurogenic dysfunction of the bladder after spinal cord injury].

AIM: to evaluate the effectiveness of fesoterodine for the prevention of autonomic dysreflexia (AD) in patients with neurogenic bladder dysfunction (NBD) after spinal cord injury (SCI). MATERIALS AND METHODS: a total of 53 patients with AD were included in the study. In the main group (n=33) patients received fesoterodine 4 mg per day for 12 weeks as a treatment for neurogenic bladder dysfunction and prevention of AD. In the control group (n=20), patients were monitored for 12 weeks without specific treatment. The assessment was based on the results of ADFSCI and NBSS questionnaires, daily blood pressure monitoring with the completion of a self-observation diary, cystometry with simultaneous monitoring of blood pressure and heart rate. RESULTS: In the main group there was a significant decrease in episodes and severity of AD according to ADFSCI questionnaire and an improvement in the quality of life according to NBSS questionnaire compared to the control group (p<0.001). Also, in the main group, the number of episodes of AD and systolic blood pressure decreased. The maximum bladder capacity and bladder compliance increased (p<0.001), and the maximum detrusor pressure and systolic blood pressure when the cystometric capacity was reached, decreased significantly (p<0.001) in the main group compared in comparison with the control group. CONCLUSION: Fesoterodine at a dosage of 4 mg for 12 weeks reduced the severity of symptoms of AD in patients with SCI and NBD, which was manifested by the stabilization of blood pressure and a decrease in the number of episodes of AD, which significantly improved the quality of life. Also, the drug led to a significant improvement in urodynamic parameters during cystometry, in the form of a decrease in detrusor pressure and an increase in cystometric capacity. We can conclude that fesoterodine is effective in the prevention of AD in patients with NBD after SCI.

Is it time to reconsider how we document pediatric uroflow studies?: A study from the SPU Voiding Dysfunction task force.

BACKGROUND: Uroflowmetry is a non-invasive study used in the diagnosis and monitoring of treatment response for lower urinary tract disorders. For optimal clinical utility, uroflow studies rely on careful clinical interpretation by a trained provider, but currently there is a lack of accepted standardized normal values for the measured uroflow parameters in children. The International Children's Continence Society proposed standardizing the terminology for uroflow curve shapes. However, the patterning of curves is largely at the physician's subjective discretion. OBJECTIVES: The aims of this study were to understand inter-rater reliability in interpreting uroflow curves and to define characteristics of uroflow curves that could be used to provide definitive criteria for uroflowmetry parameters. METHODS: All members of the SPU Voiding dysfunction Task Force were invited to contribute deidentified uroflows to a centralized HIPAA complaint receiving database. All studies were then distributed to all raters for review. Each observer's findings were recorded according to ICCS criteria (ICCS), additional readings were done using a previously reported system which defined curves as smooth or fractionated (SF) and whether the shape resembled a bell, tower, or plateau (BTP). Flow indexes (Qact/Qest) (FI) for Qmax and Qavg were generated using formulas previously reported for children 4-12 and for patients≥12 years. RESULTS: A total of 119 uroflow studies were read by 7 raters and curves were contributed from 5 sites. Kappa scores for the 5 readers from different institutions were 0.34 and 0.28 for the ICCS and BTP methods, respectively (both considered fair agreement). Kappa for smooth and fractionated curves was 0.70 (for each; considered substantial agreement), which were the two highest agreement scores obtained throughout the study. Discriminant analysis (DA) revealed that the FI Qmax was the dominant vector, and that the ICCS uroflow parameters have a total of 42.8% prediction rate in the training sample. Using DA of a smooth/fractionated system, the total prediction rates were 72% and 65.5% for smooth and fractionated, respectively. DISCUSSION: Given the poor inter-rater agreement for analyzing uroflow curve pattern based on ICCS criteria in this study and others, one may find it reasonable to consider alternative approaches to describing and characterizing uroflow curves. Our study is limited by lack of EMG and post-void residual data. CONCLUSIONS: For a more objective uroflow interpretation and comparison of studies among different centers, we recommend using our proposed system (based on FI, and smooth vs. fractionated curve pattern), which is more reliable.

Clinical and Urodynamic Predictors for Failure of Medical Management with Alpha Blockers in PBNO: A Retrospective Cohort Analysis.

OBJECTIVE: To evaluate the clinical and urodynamic variables that may predict the failure of alpha-blockers in primary bladder neck obstruction (PBNO) patients. Alpha-blockers are useful as a treatment option in patients with PBNO. Nonresponders need to undergo bladder neck incision (BNI). Little is known about the predictive factors determining the success of treatment. MATERIALS AND METHODS: This was a retrospective study, spanning over a period of 8 years. PBNO was diagnosed in the presence of a bladder outlet obstruction index (BOOI) >40 with video-urodynamic evidence of obstruction at the bladder neck. The patients were initially managed with alpha-blockers (alfuzosin and tamsulosin) for 3-6 months, and BNI contemplated when pharmacotherapy failed. The patients with upper tract changes managed with upfront BNI or clean intermittent catheterization were excluded. The data for the international prostate symptom score (IPSS), uroflowmetry, urodynamic studies, and ultrasonography of pre and post-treatment periods were reviewed. Treatment outcomes were defined as complete response (>50% improvement in Qmax and IPSS score) and partial response (30%-50% improvement in Qmax and IPSS score) at 3 or 6 months. RESULTS: Ninety-nine patients were analyzed. 21 patients underwent BNI for the failure of medical management and 31 for recurrence of symptoms at a mean follow-up of 18.8 ± 3.5 months (12-70 months). Independent predictors of failure of pharmacotherapy with alpha-blockers were age (P = .021), Pdet@Qmax (P = .015), and BOOI (P = .019). CONCLUSION: Alpha-blockers are more likely to fail in PBNO in younger patients generating higher voiding pressures and BOOI > 60.

Influence of transurethral catheters on urine pressure-flow relationships in males: A computational fluid-dynamics study.

BACKGROUND AND OBJECTIVE: In the field of urology, the pressure-flow study (PFS) is an essential urodynamics practise which requires the patient's transurethral catheterization during the voiding phase of micturition to evaluate the functionality of the lower urinary tract (LUT) and reveal the pathophysiology of its dysfunctionality. However, the literature evidences confusion regarding the interference of the catheterization on the urethral pressure-flow behaviour. METHODS: The present research study represents the first Computational Fluid-Dynamics (CFD) approach to this urodynamics issue, analysing the influence of a catheter in the male LUT through case studies which included the inter-individual and intra-individual dependence. A set of four three dimensional (3D) models of the male LUT, different in urethral diameters, and a set of three 3D models of the transurethral catheter, diverse in calibre, were developed leading to 16 CFD non-catheterized either catheterized configurations, to describe the typical micturition scenario considering both urethra and catheter characteristics. RESULTS: The developed CFD simulations showed that the urine flow field during micturition was influenced by the urethral cross-sectional area and each catheter determined a specific decrease in flow rate if compared to the relative free uroflow. CONCLUSIONS: In-silico methods allow to analyse relevant urodynamics aspects, which could not be investigated in vivo, and may support the clinical PFS to reduce uncertainty on urodynamic diagnosis.

A porcine bladder model of pre-clinical urodynamics demonstrates increased afferent nerve activity during filling.

INTRODUCTION AND OBJECTIVES: Urodynamics are the accepted gold standard for the evaluation of multiple forms of voiding dysfunction. However, the tests are expensive, invasive, poorly reproducible, and often prone to artifacts. Therefore, there is a pressing need to develop next-generation urodynamics. The purpose of this study was to develop a novel ex vivo porcine bladder urodynamics model with afferent pelvic nerve signaling that can be used as a preclinical surrogate for bladder sensation. METHODS: Porcine bladders including the ureters and vascular supply were harvested from local abattoirs using an established protocol in both male and female animals. Ex vivo bladder perfusion was performed using physiologic MOPS (3-(N-morpholino) propanesulfonic acid) buffer solution. The pelvic nerve adjacent to the bladder was grasped with micro-hook electrodes and electroneurogram (ENG) signals recorded at 20 kHz. Bladders were filled with saline at a nonphysiologic rate (100 mL/min) to a volume of 1 L using standard urodynamics equipment to simultaneously record intravesical pressure. ENG amplitude was calculated as the area under the curve for each minute, and ENG firing rate was calculated as number of spikes (above baseline threshold) per minute. At the conclusion of the experiment, representative nerve samples were removed and processed for nerve histology by a pathologist (hematoxylin and eosin and S100 stains). RESULTS: A total of 10 pig bladders were used, and nerve histology confirmed the presence of nerve in all adequately processed samples. Vesical pressure, ENG firing rate, and ENG amplitude all increased as a function of filling. During filling tertiles (low fill: min 1-3, med fill: min 4-6, and high fill: min 7-10), normalized pressures were 0.22 ± 0.04, 0.38 ± 0.05, and 0.72 ± 0.07 (cmH2O). Similarly, normalized ENG firing rates were 0.08 ± 0.03, 0.31 ± 0.06, and 0.43 ± 0.04 spikes/minute, respectively, and normalized nerve amplitudes were 0.11 ± 0.06, 0.39 ± 0.06, and 0.56 ± 0.14) µV, respectively. Strong relationships between average normalized pressure values and averaged normalized ENG firing rate (r2 = 0.66) and average normalized ENG amplitude (r2 = 0.8) were identified. CONCLUSIONS: The ex vivo perfused porcine bladder can be used as a preclinical model for the development of next-generation urodynamics technologies. Importantly, the model includes a reproducible method to measure afferent nerve activity that directly correlates with intravesical pressure during filling and could potentially be used as a surrogate measure of bladder sensation.

Detrusor underactivity is associated with metabolic syndrome in aged primates.

Lower urinary tract (LUT) dysfunction is prevalent in the elderly population, and clinical manifestations include urinary retention, incontinence, and recurrent urinary tract infections. Age-associated LUT dysfunction is responsible for significant morbidity, compromised quality of life, and rising healthcare costs in older adults, but its pathophysiology is not well understood. We aimed to investigate the effects of aging on LUT function by urodynamic studies and metabolic markers in non-human primates. Adult (n = 27) and aged (n = 20) female rhesus macaques were evaluated by urodynamic and metabolic studies. Cystometry showed detrusor underactivity (DU) with increased bladder capacity and compliance in aged subjects. Metabolic syndrome indicators were present in the aged subjects, including increased weight, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and high sensitivity C-reactive protein (hsCRP), whereas aspartate aminotransferase (AST) was unaffected and the AST/ALT ratio reduced. Principal component analysis and paired correlations showed a strong association between DU and metabolic syndrome markers in aged primates with DU but not in aged primates without DU. The findings were unaffected by prior pregnancies, parity, and menopause. Our findings provide insights into possible mechanisms for age-associated DU and may guide new strategies to prevent and treat LUT dysfunction in older adults.

Determination of tibial somatosensory evoked potentials predicts detrusor sphincter dyssynergia in children with neurogenic bladder dysfunction.

INTRODUCTION: Tibial somatosensory evoked potentials (SEP) are used to identify the neurological status and tethered cord (TC) in patients with spina bifida (SB). Its significance in contributing to the interpretation of urodynamics to determine bladder status is unknown. This study aimed to determine the correlation between SEP and urodynamics in children with SB. MATERIAL AND METHODS: SEP and urodynamic results, for differential diagnosis of TC, were evaluated. SEP scores were correlated with urodynamic findings. SEP results were scored from 1 to 6, with 1, denoting a favorable score and 6, an unfavorable score. Age, gender, detrusor, and sphincter activities in urodynamics were noted. Results were analyzed using the χ2 test and logistic regression analysis. Receiver operating characteristic (ROC) curve was formed to get a valid threshold for the SEP score to predict the urodynamic condition. RESULTS: There were 44 SB patients for whom SEP was done for differential diagnosis of TC. Fifteen patients who did not meet the inclusion criteria were excluded from the study. SB aperta was present in 17 patients and occulta in 12, respectively. The patients had a mean age of 6.6 ± 3.2 years. There were 13 boys and 16 girls. A strong correlation was found between high SEP scores and detrusor sphincter dyssynergia (p < 0.001). A SEP score over 3.5 was found to be 93% sensitive and 73% specific to predict this correlation. There was no relationship between detrusor activity and SEP scores (p = 0.18). DISCUSSION: Tibial SEP is an important noninvasive adjunct tool for the diagnosis of TC in patients with SB. Urodynamic studies are the gold standard in the evaluation of bladder status in neurogenic bladder dysfunction due to SB. Detrusor sphincter dyssynergia may be regarded as a sign of severe spinal cord injury in these patients. CONCLUSION: Our findings suggest that in children with neurogenic bladder, high SEP scores may predict the presence of detrusor sphincter dyssynergia but not the status of detrusor function while providing pathophysiological evidence for neural injury.