Can Videourodynamics shape management in refractory pediatric lower urinary tract dysfunction?

INTRODUCTION: Bladder dysfunction, or more specifically lower urinary tract dysfunction (LUTD), remains a common reason for pediatric urology consultation, and the management of these patients is time consuming and frustrating for patients, families and providers alike. But what happens when the patient proves refractory to current treatment modalities? Is there a role for the use of videourodynamics (VUDS) to help guide therapy in the patient with refractory voiding dysfunction, and if so how might we select patients for this invasive study in order to increase the yield of useful information? OBJECTIVES: To determine the role, if any, for VUDS in the evaluation of pediatric patients with refractory LUTD and to identify parameters that might be used to select patients for this invasive study in order to increase the yield of useful information. STUDY DESIGN: Through our IRB-approved prospectively maintained urodynamics database, we retrospectively identified 110 patients with non-neurogenic LUTD over a period from 2015 to 2022 who underwent VUDS. We excluded patients with known neurologic or anatomic lesions and developmental delay. RESULTS: There were 76 females and 34 males (69%/31%) and their average age at the time of the study was 10.5 years ± 4 with a median age of 7.3 years. Patients had been followed for a mean of 5.9 ± 3.5 office visits prior to obtaining the VUDS and reported a mean Dysfunction Voiding and Incontinence Symptom Score (DVISS) of 15.6 ± 6.7 before the VUDS. VUDS resulted in a change in management in 86 of these 110 patients (78%). Management changes included a change in medication (53/110), consideration of CIC (11/110), PTENS (1/110) and surgery (14/110). As shown in the Figure, the DVISS score was significantly higher and the number of office visits prior to VUDS was significantly higher in the 86 patients whose management was changed versus the 24 patients in whom management did not change (P < 0.02). CONCLUSION: This retrospective analysis suggests that criteria for selecting these patients include: 1) long standing urinary incontinence that is refractory to biofeedback and medications, 2) ≥6 visits to LUTD clinic with no improvement, and 3) LUT symptom score of ≥16. Our findings suggest these criteria identify a cohort of patients in which a VUDS evaluation for the child with refractory LUTD can offer a more exact diagnosis that can shape management.

Who needs an ultrasound? Using patient symptom questionnaire & UTI history to determine when to obtain an RBUS in children with non-neurogenic lower urinary tract dysfunction.

INTRODUCTION: Non-neurogenic lower urinary tract dysfunction (LUTD) is one of the most common reasons for presentation to a pediatric urologist, affecting up to 20% of children. Predicting who will benefit from RBUS as part of their work-up is challenging as the majority will have normal imaging. OBJECTIVE: Our objective was to assess the utility of using the Dysfunctional Voiding and Incontinence Scoring System (DVISS) and urinary tract infection (UTI) history to predict which LUTD patients were most likely to have an abnormal RBUS as well as determine a DVISS cutoff to aid in making this prediction. We hypothesized that higher DVISS scores and a positive urinary tract infection (UTI) history would be associated with increased likelihood of RBUS abnormality. STUDY DESIGN: We retrospectively reviewed outpatients seen for LUTD from 5/2014-1/2016 who received an RBUS. Association between prior UTI, DVISS score, gender, and race and RBUS abnormality were evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curves were created to evaluate the predictive model and a Youden index calculated to determine the optimal cutoff for DVISS score to predict abnormal RBUS. RESULTS: 15 of 333 patients (4.5%) had a clinically significant RBUS abnormality. Significantly more patients with abnormal RBUS had a positive UTI history and median DVISS was higher. UTI history and DVISS score were associated with RBUS abnormality whereas neither gender nor race were. A DVISS score cutoff of 12 was determined to be ideal for predicting abnormal imaging. Using DVISS≥12 and positive UTI history, patients with both risk factors were significantly more likely to have an abnormal RBUS than those with zero or one risk factor (Figure). DISCUSSION: To the best of our knowledge this is the first study to try to identify risk factors associated with RBUS abnormality in pediatric LUTD patients and create an evidence-based approach to imaging these patients. We found both DVISS cutoff ≥12 and positive UTI history to be useful to risk stratify LUTD patients' likelihood of abnormal RBUS. Limitations include the study's retrospective nature as well as the fact the population was drawn from a tertiary care pediatric hospital with a large referral population and the fact that the decision to order an RBUS was based on individual clinician preference and decision making. CONCLUSIONS: We found that DVISS score≥12 and UTI history are useful in guiding the decision to obtain RBUS in pediatric LUTD patients.

Automated Society of Fetal Urology (SFU) grading of hydronephrosis on ultrasound imaging using a convolutional neural network.

INTRODUCTION: Grading of hydronephrosis severity on postnatal renal ultrasound guides management decisions in antenatal hydronephrosis (ANH). Multiple systems exist to help standardize hydronephrosis grading, yet poor inter-observer reliability persists. Machine learning methods may provide tools to improve the efficiency and accuracy of hydronephrosis grading. OBJECTIVE: To develop an automated convolutional neural network (CNN) model to classify hydronephrosis on renal ultrasound imaging according to the Society of Fetal Urology (SFU) system as potential clinical adjunct. STUDY DESIGN: A cross-sectional, single-institution cohort of postnatal renal ultrasounds with radiologist SFU grading from pediatric patients with and without hydronephrosis of stable severity was obtained. Imaging labels were used to automatedly select sagittal and transverse grey-scale renal images from all available studies from each patient. A VGG16 pre-trained ImageNet CNN model analyzed these preprocessed images. Three-fold stratified cross-validation was used to build and evaluate the model that was used to classify renal ultrasounds on a per patient basis into five classes based on the SFU system (normal, SFU I, SFU II, SFU III, or SFU IV). These predictions were compared to radiologist grading. Confusion matrices evaluated model performance. Gradient class activation mapping demonstrated imaging features driving model predictions. RESULTS: We identified 710 patients with 4659 postnatal renal ultrasound series. Per radiologist grading, 183 were normal, 157 were SFU I, 132 were SFU II, 100 were SFU III, and 138 were SFU IV. The machine learning model predicted hydronephrosis grade with 82.0% (95% CI: 75-83%) overall accuracy and classified 97.6% (95% CI: 95-98%) of the patients correctly or within one grade of the radiologist grade. The model classified 92.3% (95% CI: 86-95%) normal, 73.2% (95% CI: 69-76%) SFU I, 73.5% (95% CI: 67-75%) SFU II, 79.0% (95% CI: 73-82%) SFU III, and 88.4% (95% CI: 85-92%) SFU IV patients accurately. Gradient class activation mapping demonstrated that the ultrasound appearance of the renal collecting system drove the model's predictions. DISCUSSION: The CNN-based model classified hydronephrosis on renal ultrasounds automatically and accurately based on the expected imaging features in the SFU system. Compared to prior studies, the model functioned more automatically with greater accuracy. Limitations include the retrospective, relatively small cohort, and averaging across multiple imaging studies per patient. CONCLUSIONS: An automated CNN-based system classified hydronephrosis on renal ultrasounds according to the SFU system with promising accuracy based on appropriate imaging features. These findings suggest a possible adjunctive role for machine learning systems in the grading of ANH.

Deep Learning of Videourodynamics to Classify Bladder Dysfunction Severity in Patients With Spina Bifida.

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.

Ultrasound-Estimated Bladder Weight Correlates With Videourodynamic Studies in Neurogenic Bladder Dysfunction.

PURPOSE: This retrospective study was designed to evaluate which lower urinary tract ultrasound parameter(s) could predict the results of invasive urodynamic testing which are the current reference standard in the evaluation of bladder dysfunction in children with spina bifida. MATERIALS AND METHODS: Fifty eight children with spina bifida undergoing video urodynamic evaluation and a renal bladder ultrasound as their standard of care were evaluated. Quantitative and qualitative ultrasound parameters were then correlated with the videourodynamic study results which served as the reference standard. RESULTS: For bladders with ending storage pressures above 15 cm H2 O, there were increases in these ultrasound measured parameters: 1) bladder mass (P = .00019), 2) bladder/body mass ratio (P = .0059), and 3) wall thickness (P = .01). We defined the storage cost as the final storage pressure divided by the percentage of expected bladder capacity attained. These data were analyzed to compute receiver operating curves with assuming end storage pressures cutoff points of 15, 20, 30, and 40 cm H2 O. The optimal area under the curve was found for a bladder weight of 65 g and a pressure cutoff of 30 cm H2 O with a sensitivity of 75% with a specificity of 84%. CONCLUSION: Bladder weight is independent of luminal volume, can be normalized to body weight, and may serve as a clinically valuable tool for noninvasive screening to define a subset of patients with neurogenic bladder with a higher likelihood of having abnormal videourodynamic results.

Impact of Race, Gender, and Socioeconomic Status on Symptom Severity at Time of Urologic Referral.

BACKGROUND AND OBJECTIVES: The Dysfunctional Voiding and Incontinence Scoring System (DVISS) is a validated tool to evaluate lower urinary tract dysfunction (LUTD) severity in children. DVISS provides a quantitative score (0-35) including a quality-of-life measure, with higher values indicating more/worse symptoms. Clinically, variability exists in symptom severity when patients present to pediatric urology with LUTD. We hypothesized that symptom severity at consultation varied based on race, gender, and/or socioeconomic status. METHODS: All urology encounters at a single institution with completed modified DVISS scores 6/2015-3/2018 were reviewed. Initial visits for patients 5-21 years old with non-neurogenic LUTD were included. Patients with neurologic disorders or genitourinary tract anomalies were excluded. Wilcoxon rank sum tests compared scores between White and Black patients and between male and female patients. Multiple regression models examined relationships among race, gender, estimated median household income, and insurance payor type. All statistics were performed using Stata 15. RESULTS: In total, 4086 initial patient visits for non-neurogenic LUTD were identified. Median DVISS scores were higher in Black (10) versus White (8) patients (p < 0.001). Symptom severity was higher in females (9) versus males (8) (p < 0.001). When estimated median income and insurance payer types were introduced into a multiple regression model, race, gender, and insurance payer type were significantly associated with symptom severity at presentation. CONCLUSIONS: Race, gender, and socioeconomic status significantly impact LUTS severity at the time of urologic consultation. Future studies are needed to clarify the etiologies of these disparities and to determine their clinical significance.

Ultrasound shear wave elastography cannot discriminate between low- and high-pressure neurogenic bladders.

BACKGROUND: Patients with neurogenic bladders are monitored with renal bladder ultrasounds and video urodynamics studies (VUDS) to assess upper urinary tract injury. Ultrasound shear wave elastography (US-SWE) can assess tissue stiffness. If bladder compliance is affected by bladder wall fibrosis and stiffening, then high-pressure bladders may be detectable by US-SWE therefore reducing the need for VUDS in some patients. OBJECTIVE: To determine if US-SWE can differentiate between low- and high-pressure bladders and hence be used for noninvasive assessment of neurogenic bladder in children. STUDY DESIGN: Prospective study of patients with neurogenic bladder undergoing clinically indicated VUDS between February and July of 2017. During VUDS, bladder wall US-SWE was measured at different filling percentages of estimated bladder capacity (EBC). The bladders were divided into cohorts according to the detrusor muscle pressure (Pdet) reached at the maximum bladder capacity: normal (1 to <15 cmH2O) and abnormal (≥15 cmH2O) pressure. T-test was used to compare elastography values at different bladder volumes and Pdet; (statistical significance set at p < 0.05). RESULTS: 30/31 enrolled children completed the protocol. With an empty bladder, as well as at all other bladder volumes, no relationship was observed between Pdet and mean SWE of the anterior or posterior bladder wall. At maximum bladder capacity, there was no difference between mean SWE values of the anterior or posterior bladder walls in those with normal pressure, 2.97 m/s (SD ± 0.82) and 1.96 m/s (SD ± 0.75), compared to those with abnormal pressures 3.08 m/s (SD ± 0.84) and 2.39 m/s (SD ± 0.96), p = 0.75 and p = 0.2, respectively. DISCUSSION: We found no difference between SWE values of either the anterior or posterior bladder wall in neurogenic bladders with normal and abnormal filling pressures measured during VUDS. Our study differs from previously reported studies with more positive results in that our cut-off for abnormal bladder pressure was (Pdet ≥15 cmH2O). This is lower than the more commonly used leak point pressure of 40 cmH2O because our practice is to intervene earlier. Moreover, SWE would be most useful if it can identify changes before the bladder has reached such severe conditions, to allow for early intervention. Additional differences between ours and other studies include US manufacturer and younger age of the participating children. CONCLUSIONS: US-SWE, while feasible, was not able to discriminate between low- and high-pressure bladders. Moreover, US-SWE did not show significant correlation with the current gold standard, VUDS.

Somatostatin Neurons in the Mouse Pontine Nucleus Activate GABAA Receptor Mediated Synaptic Currents in Locus Coeruleus Neurons.

The pontine nuclei comprising the locus coeruleus (LC) and Barrington's nucleus (BRN) amongst others form the neural circuitry(s) that coordinates arousal and voiding behaviors. However, little is known about the synaptic connectivity of neurons within or across these nuclei. These include corticotropin-releasing factor (CRF+) expressing neurons in the BRN that control bladder contraction and somatostatin expressing (SST+) neurons whose role in this region has not been discerned. To determine the synaptic connectivity of these neurons, we employed optogenetic stimulation with recordings from BRN and LC neurons in brain stem slices of channelrhodopsin-2 expressing SST or CRF neurons. Optogenetic stimulation of CRF+ BRN neurons of Crf Cre ;chr2-yfp mice had little effect on either CRF+ BRN neurons, CRF- BRN neurons, or LC neurons. In contrast, in Sst Cre ;chr2-yfp mice light-activated inhibitory postsynaptic currents (IPSCs) were reliably observed in a majority of LC but not BRN neurons. The GABAA receptor antagonist, bicuculline, completely abolished the light-induced IPSCs. To ascertain if these neurons were part of the neural circuitry that controls the bladder, the trans-synaptic tracer, pseudorabies virus (PRV) was injected into the bladder wall of Crf Cre ;tdTomato or Sst Cre ;tdTomato mice. At 68-72 h post-viral infection, PRV labeled neurons were present only in the BRN, being preponderant in CRF+ neurons with few SST+ BRN neurons labeled from the bladder. At 76 and 96 h post-virus injection, increased labeling was observed in both BRN and LC neurons. Our results suggest SST+ neurons rather than CRF+ neurons in BRN can regulate the activity of LC neurons.

Corticotropin-Releasing Hormone from the Pontine Micturition Center Plays an Inhibitory Role in Micturition.

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.

Single institution experience with telemedicine for pediatric urology outpatient visits: Adapting to COVID-19 restrictions, patient satisfaction, and future utilization.

INTRODUCTION: Widespread utilization of telemedicine in our practice to date has been limited to the evaluation of certain post-surgical patients. The COVID-19 pandemic acutely stressed our established system and required us to enhance our utilization of telemedicine. We hypothesized that expansion of telemedicine to new and follow up patient visits for pediatric urology could be done effectively in a way that satisfied patient and parental expectations. MATERIALS AND METHODS: Using a pre-COVID-19 established telemedicine program based in our electronic medical record (EMR), patients and providers transitioned to primarily virtual visits when clinically appropriate. Guidelines were formulated to direct patient scheduling, provider and staff education was provided, including a process map designed for multiple providers to complete video visits (VV), and the EMR was redesigned to incorporate telehealth terminology. The number of VV per provider was recorded using the electronic medical record, and patient reported outcomes (PRO) were measured using a standardized questionnaire. RESULTS: A total of 631 VV met inclusion criteria during the period of May 2018-April 2020. This included 334 follow up, 172 new, and 125 postoperative visits. The median age of patients at time of visit was 7 years (IQR 2-12 years), median visit time was 20 min (IQR 15-30 min), and the median travel distance saved by performing a VV was 12.2 miles (IQR 6.3-26.8 miles). Diagnoses were varied and included the entire breadth of a standard pediatric urology practice. The PRO questionnaire was completed for 325 of those patient visits. Families reported a high overall satisfaction with the video visits (median score of 10 out of 10) and felt that the visit met their child's medical needs. 90% stated that they would strongly recommend a telehealth visit to other families. Patients and parents reported benefits of VV including decreased travel costs and less time taken off from work and school. CONCLUSION: The EMR enabled nimble redirection of clinical care in the setting of a global pandemic. The enhanced use of telemedicine has proved to be an alternative method to provide care for pediatric urology patients. Families indicate a high degree of satisfaction with this technology in addition to significant time and cost savings. Telemedicine should remain a key aspect of medical care and expanded from post-operative visits to new patient and follow up visits, even as we return to our normal practices as the pandemic restrictions soften.

Total Motile Sperm Count in Adolescent Boys with Varicocele is Associated with Hormone Levels and Total Testicular Volume.

PURPOSE: The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. MATERIALS AND METHODS: We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. RESULTS: A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. CONCLUSIONS: Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.

Management of Vesicoureteral Reflux in a Patient With Recurrent Febrile Urinary Tract Infections, Neurogenic Bladder, and Ureteral Triplication.

Ureteral triplication is a rare anomaly with about 100 total cases reported in the literature. In this case presentation, we present a case of ureteral triplication in a young female with a history of neurogenic bladder secondary to L5 lipomeningocele who presented with recurrent febrile urinary tract infections (UTIs) and vesicoureteral reflux despite antibiotic prophylaxis. Given her high grade reflux, she underwent ureteral reimplantation which ultimately led to resolution of her UTIs and reflux. Later in her clinical course, toilet training unmasked additional bladder dysfunction and she was successfully managed with clean intermittent catheterization and anticholinergics. To the best of our knowledge, this is the first case report to describe ureteral triplication, recurrent febrile UTIs and vesicoureteral reflux in the setting of a concomitant neurogenic bladder with a successful outcome.

Urine Proteomics: Evaluation of Different Sample Preparation Workflows for Quantitative, Reproducible, and Improved Depth of Analysis.

The growing field of urinary proteomics shows promise to expand the number of biomarkers for the diagnosis and prognosis of a number of human diseases. With the rapid developments in mass spectrometry methods for proteome quantification, there exists an opportunity for improved sample processing and separation workflows to make important contributions to urine proteomic analyses. Here we evaluate the performance of four sample preparation methods: MStern, PreOmics in-StageTip (iST), suspension-trapping (S-Trap), and conventional urea In-Solution trypsin hydrolysis for nondepleted urine samples. Data-dependent acquisition (DDA) mode on a QExactive HF mass spectrometer was used for single-shot label-free data acquisition. Our results demonstrate a high degree of reproducibility within each workflow. PreOmics iST yields the best digestion efficiency, whereas the S-Trap workflow gives the greatest number of peptide and protein identifications. Using the S-Trap method and starting with ∼0.5 mL, we identify ∼1500 protein groups and ∼17 700 peptides from DDA analysis with a single injection on the mass spectrometer.

How early is early? Effect of oxybutynin on bladder dynamics within the first year of life in patients with spina bifida.

INTRODUCTION: Early proactive treatment of patients with high-risk neurogenic bladder from spina bifida (SB) may preserve renal function and decrease the need for bladder augmentation later in life. Timing of initiation of anticholinergic therapy (AC) medication and clean intermittent catheterization (CIC) is variable and based on imprecise studies. The authors hypothesized that initiation of AC after the initial video-urodynamic study (VUDS) may benefit bladder capacity even in children who do not meet the standard hostile criteria for starting AC. STUDY DESIGN: A retrospective review of a prospectively maintained VUDS database from August 2015 to March 2019 was performed. Patients with SB who had undergone initial VUDS between 1 and 7 months of age and had a subsequent follow-up study between 9 and 18 months of age were included. Multiple VUDS and clinical parameters including expected bladder capacity, actual capacity reached, pressure at actual capacity, presence of detrusor overactivity, presence of urinary tract dilation and reflux, and whether or not AC was started were extracted and compared. P-value of <0.05 was considered statistically significant. RESULTS: A total of 69 patients completed an initial study at median age of 2 months, and follow-up study at median age of 13 months. Anticholinergic therapy was started in 21 patients (10 F, 11 M). Decision to initiate AC was at discretion of the attending pediatric urologist performing the VUDS in real time. Changes between the initial and repeat VUDS are listed in the summary table below. Adverse effects of AC were reported in 25% (5/21) patients: urinary retention/UTIs (3), allergic reaction (1), and fatigue (1). DISCUSSION: The authors findings suggest that AC stabilizes storage pressure for those who initially have a higher storage pressure, while in those with initial low storage pressures, storage pressures worsened over time in the absence of AC. Patients started on AC experienced a faster rate of increase in bladder capacity. Limitations to this study included the unknown long term and sustainability of the improvement in bladder parameters, the lack of uniform criteria for the initiation of AC or CIC, and an unknown long-term degree of upper tract protection. CONCLUSION: This study found early initiation of AC in SB at 2 months of age had significant positive effects on growth of bladder capacity and stabilization of storage pressure. However, long-term effects of AC are still undetermined, and thus, longitudinal studies are needed to understand the precise indications for initiation of early AC treatment.

Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2.

Bladder dysfunction is associated with the overexpression of the intermediate filament (IF) proteins desmin and vimentin in obstructed bladder smooth muscle (BSM). However, the mechanisms by which these proteins contribute to BSM dysfunction are not known. Previous studies have shown that desmin and vimentin directly participate in signal transduction. In this study, we hypothesized that BSM dysfunction associated with overexpression of desmin or vimentin is mediated via c-Jun N-terminal kinase (JNK). We employed a model of murine BSM tissue in which increased expression of desmin or vimentin was induced by adenoviral transduction to examine the sufficiency of increased IF protein expression to reduce BSM contraction. Murine BSM strips overexpressing desmin or vimentin generated less force in response to KCl and carbachol relative to the levels in control murine BSM strips, an effect associated with increased JNK2 phosphorylation and reduced myosin light chain (MLC20 ) phosphorylation. Furthermore, desmin and vimentin overexpressions did not alter BSM contractility and MLC20 phosphorylation in strips isolated from JNK2 knockout mice. Pharmacological JNK2 inhibition produced results qualitatively similar to those caused by JNK2 knockout. These findings suggest that inhibition of JNK2 may improve diminished BSM contractility associated with obstructive bladder disease.

Neuroscience: A New Golden Age for Neurourology.

The pons contains neurons that control urinary bladder function. Using the modern tools of neurobiology, new studies reveal a heterogeneous population of neurons which interact with higher centers and the sacral and lumbar spinal cord to coordinate complex voiding behaviors.