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Complementary and alternative therapy (CAT) methods for children with autism spectrum disorders (ASD) are widespread in European countries and the Russian Federation; however, their efficacy and safety is not routinely considered by parents and clinicians when recommended or used. The current narrative review presents the most widely known CAT interventions for children with ASD synthesizing data from meta-analyses, systematic reviews, and randomized controlled trials obtained from the PubMed database based on the safety-efficacy model. We have found that, of the reviewed CATs, only the melatonin intervention can be considered safe and effective for children with ASD with comorbid sleep problems. The methods that were classified as safe but had inconclusive efficacy are recommended to be implemented only when they do not interfere with front line treatment for ASD, Applied Behavior Analysis (ABA). Methods with the lack of current evidence for the efficacy such as auditory integration therapies, bioacoustic correction, sensory integration therapy, micropolarization, animal assisted therapy, and dietary interventions should not be recommended as alternative treatments and can only be used as complimentary to ABA-based interventions. We advise against the use of chelation, hyperbaric oxygen therapy, and holding therapy due their documented harmful psychological and physical effects. When considering CAT for ASD we recommend parents and clinicians use the criteria suggested by Lofthouse and colleagues [59]: only the therapies that are safe, easy, cheap, and sensible can be recommended and used, as opposed to therapies that are risky, unrealistic, difficult, or expensive that should not be recommended or utilized.

Abstract Background Protein expression profiles throughout 28 days of peripheral nerve regeneration were characterized using an established rat sciatic nerve transection injury model. Reverse phase protein microarrays were used to identify the spatial and temporal expression profile of multiple proteins implicated in peripheral nerve regeneration including growth factors, extracellular matrix proteins, and proteins involved in adhesion and migration. This high-throughput approach enabled the simultaneous analysis of 3,360 samples on a nitrocellulose-coated slide. Results The extracellular matrix proteins collagen I and III, laminin gamma-1, fibronectin, nidogen and versican displayed an early increase in protein levels in the guide and proximal sections of the regenerating nerve with levels at or above the baseline expression of intact nerve by the end of the 28 day experimental course. The 28 day protein levels were also at or above baseline in the distal segment however an early increase was only noted for laminin, nidogen, and fibronectin. While the level of epidermal growth factor, ciliary neurotrophic factor and fibroblast growth factor-1 and -2 increased throughout the experimental course in the proximal and distal segments, nerve growth factor only increased in the distal segment and fibroblast growth factor-1 and -2 and nerve growth factor were the only proteins in that group to show an early increase in the guide contents. As expected, several proteins involved in cell adhesion and motility; namely focal adhesion kinase, N-cadherin and β-catenin increased earlier in the proximal and distal segments than in the guide contents reflecting the relatively acellular matrix of the early regenerate. Conclusions In this study we identified changes in expression of multiple proteins over time linked to regeneration of the rat sciatic nerve both demonstrating the utility of reverse phase protein arrays in nerve regeneration research and revealing a detailed, composite spatiotemporal expression profile of peripheral nerve regeneration.

Numerous behavioral studies have demonstrated a rhythmic priming effect (RPE) on grammatical processing using grammaticality judgment tasks (GJT), where participants performed better following regular rhythmic sequences compared to baseline conditions or irregular rhythmic sequences (i.e. auditory rhythmic sequences with violated metrical structure). Only a few studies, however, have explored neurophysiological RPE in grammatical processing. Such neurophysiological investigations have been limited to GJT presented auditorily, have been primarily focused on the French- and German-speaking adult participants, and have rarely used baseline nonpriming conditions. The objective of the present study was to investigate neurophysiological correlates of the RPE in the GJT presented in visual modality. In the current study, we registered a 128-channel electroencephalogram while Russian-speaking adolescents performed a visual GJT, where each sentence was presented word by word in a self-paced manner. Before each experimental block, participants listened to regular rhythmic sequences, irregular rhythmic sequences, or silence. We observed that the late negativity in the event-related potential was larger for the ungrammatical condition compared to the grammatical condition only after the presentation of irregular rhythmic sequences. This effect, referred to as the N600 component in previous research, has been associated with increased cognitive complexity. In conclusion, results suggest that exposure to irregular rhythmic stimulation may lead to increased cognitive demand. This is attributed to the complexity associated with concurrently executing the GJT and managing rhythmic disruption, consequently increasing the strain on working memory resources., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale., Objective: We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals., Study Design: We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty., Results: In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend., Discussion: Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly., Conclusions: Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed., Competing Interests: Conflicts of interest No authors have any conflicts of interest to disclose., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Backgrounds: Urinary Tract Dilation (UTD) classification has been designed to be a more objective grading system to evaluate antenatal and post-natal UTD. Due to unclear association between UTD classifications to specific anomalies such as vesico-ureteral reflux (VUR), management recommendations tend to be subjective., Objective: We sought to develop a model to reliably predict VUR from early post-natal ultrasound., Study Design: Radiology records from single institution were reviewed to identify infants aged 0-90 days undergoing early ultrasound for antenatal UTD. Medical records were reviewed to confirm diagnosis of VUR. Primary outcome defined as dilating (≥Gr3) VUR. Exclusion criteria include major congenital urologic anomalies (bilateral renal agenesis, horseshoe kidney, cross fused ectopia, exstrophy) as well as patients without VCUG. Data were split into training/testing sets by 4:1 ratio. Machine learning (ML) algorithm hyperparameters were tuned by the validation set., Results: In total, 280 patients (540 renal units) were included in the study (73 % male). Median (IQR) age at ultrasound was 27 (18-38) days. 66 renal units were found to have ≥ grade 3 VUR. The final model included gender, ureteral dilation, parenchymal appearance, parenchymal thickness, central calyceal dilation. The model predicted VUR with AUC at 0.81(0.73-0.88) on out-of-sample testing data. Model is shown in the figure., Discussion: We developed a ML model that can predict dilating VUR among patients with hydronephrosis in early ultrasound. The study is limited by the retrospective and single institutional nature of data source. This is one of the first studies demonstrating high performance for future diagnosis prediction in early hydronephrosis cohort., Conclusions: By predicting dilating VUR, our predictive model using machine learning algorithm provides promising performance to facilitate individualized management of children with prenatal hydronephrosis, and identify those most likely to benefit from VCUG. This would allow more selective use of this test, increasing the yield while also minimizing overutilization., Competing Interests: Conflict of interest No coauthors have any personal or financial conflicts of interest to disclose., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Aim: To explore the association between presence and severity of lower limb spasticity (LLS) and risk of orchidopexy for cryptorchidism among people with cerebral palsy (CP) and to further define the cremasteric muscle spasticity theory., Method: We queried the Pediatric Health Information System database for male patients with CP, stratified patients into those with/without LLS, and compared groups for orchidopexy occurrence. Comparative statistics were performed using χ 2 and Mann-Whitney U tests for categorical and continuous variables respectively. The association between orchidopexy and spasticity type was investigated using logistic regression., Results: In total, 44 561 males with CP were identified. Of these, 1.6% underwent orchidopexy (median age: 7 years 8 months [interquartile range: 4 years 6 months-11 years 4 months]). LLS presence was significantly associated with higher orchidopexy rate compared to spasticity absence (odds ratio [OR] = 1.33 [1.10-1.59], p = 0.003). Among 7134 patients with LLS, intervention was significantly associated with higher orchidopexy rate (injection procedures: OR = 2.47 [2.27-6.39], p = 0.034; surgical procedure: OR = 2.60 [1.22-6.76], p = 0.026). LLS groin proximity was significantly associated with higher orchidopexy rate (OR = 2.52 [1.42-4.96], p = 0.003)., Interpretation: A strong association exists between LLS presence and severity and orchidopexy risk among people with CP. These findings support a cremasteric spasticity hypothesis as an important factor of cryptorchidism in CP. Providers should continue to examine for cryptorchidism in males with CP as they age., What This Paper Adds: Lower limb spasticity (LLS) is associated with higher orchidopexy rate in cerebral palsy. Orchidopexy rate was higher in more severe LLS. Orchidopexy rate was higher in more proximal LLS., (© 2023 Mac Keith Press.)

Background: Management of the adolescent varicocele focuses on optimizing fertility potential, but to date there is limited data on the success of varicocelectomy on optimizing semen parameters for individual adolescent patients. We reviewed our database of over 1600 adolescent varicocele patients to find those with pre- and postoperative semen analyses to determine the impact of varicocele correction., Methods: 15 Tanner stage V patients with unilateral clinically apparent left-sided with pre- and postoperative semen analyses were identified. Mixed models were used to compare semen parameters pre- and post-varicocelectomy in patients with successful management., Results: Complete elimination of the varicocele was achieved in 12/15 (80%) patients. Three patients had persistent varicocele (with down-grading in two) and declined further intervention. Median time between pre- and postoperative semen analyses was 24.2 months. For those with successful varicocele correction, total motile sperm count (TMSC) improved in all but one (Figure 1), with an average increase of 44.0 million (95% CI: 18.7-69.3) in post-varicocelectomy analyses compared to pre-varicocelectomy (p = 0.0016). Mean percent improvement was 649.2%. It went from abnormal to normal (≥20 million/cc) in 55.6% (5/9). For the three patients with persistent varicocele, one had improved TMSC from abnormal to normal range, one had worsening within normal range, and one had effectively no change., Conclusion: Successful correction of adolescent varicocele may improve TMSC. In over half of our institution's cases, an abnormal value normalized. Surgical intervention may be considered for adolescent varicoceles associated with abnormal semen parameters., Levels of Evidence: Level III., Type of Study: Treatment study., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Patients with penile conditions comprise a significant proportion of any pediatric urology practice, and physical examination is the mainstay of diagnosis for such conditions. While the rapid adoption of telemedicine (TM) facilitated access to pediatric urology care during the pandemic, the accuracy of TM-based diagnosis for pediatric penile anatomy and pathology has not been studied. Our aim was to characterize the diagnostic accuracy of TM-based evaluation of pediatric penile conditions by comparing diagnosis during the initial virtual visit (VV) with a subsequent in-person visit (IPV). We also sought to assess the agreement between scheduled and actual surgical procedure performed., Methods: A single-institution prospective database of male patients less than 21 years of age who presented for evaluation of penile conditions between August 2020 and December 2021 was analyzed. Patients were included if they had an IPV with the same pediatric urologist within 12 months of the initial VV. Diagnostic concordance was based on a surgeon-reported survey of specific penile diagnoses, completed at both initial VV and follow-up IPV. Surgical concordance was assessed based on the proposed versus billed CPT code(s)., Results: Median age among 158 patients was 10.6 months. The most frequent VV diagnoses were penile adhesions (n = 37), phimosis (n = 26), "other" (n = 24), post-circumcision redundancy (n = 18), and buried penis (n = 14). Initial VV and subsequent IPV diagnoses were concordant in 40.5% (64/158); 40/158 (25%) had partial concordance (at least one diagnosis matched). There was no difference in age, race, ethnicity, median time between visits, or device type between patients with concordant vs. discordant diagnoses. Of 102 patients who underwent surgery, 44 had VV only while 58 had IPV prior to surgery. Concordance of scheduled versus actual penile surgery was 90.9% in those patients who only had a VV prior to surgery. Overall, surgery concordance was lower among those with hypospadias repairs vs. non-hypospadias surgery (79.4% vs. 92.6%, p = 0.05)., Conclusion: Among pediatric patients being evaluated by TM for penile conditions, there was poor agreement between VV-based and IPV-based diagnoses. However, besides hypospadias repairs, agreement between planned and actual surgical procedures performed was high, suggesting that TM-based assessment is generally adequate for surgical planning in this population. These findings leave open the possibility that, among patients not scheduled for surgery or IPV, certain conditions might be misdiagnosed or missed entirely., Competing Interests: Conflicts of interest None., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: ERAS (enhanced recovery after surgery) protocols are designed to optimize perioperative care and expedite recovery. Historically, complete primary repair of bladder exstrophy has included postoperative recovery in the intensive care unit and extended length of stay. We hypothesized that instituting ERAS principles would benefit children undergoing complete primary repair of bladder exstrophy, decreasing length of stay. We describe implementation of a complete primary repair of bladder exstrophy-ERAS pathway at a single, freestanding children's hospital., Materials and Methods: A multidisciplinary team developed an ERAS pathway for complete primary repair of bladder exstrophy, which launched in June 2020 and included a new surgical approach that divided the lengthy procedure into 2 consecutive operative days. The complete primary repair of bladder exstrophy-ERAS pathway was continuously refined, and the final pathway went into effect in May 2021. Post-ERAS patient outcomes were compared with a pre-ERAS historical cohort (2013-2020)., Results: A total of 30 historical and 10 post-ERAS patients were included. All post-ERAS patients had immediate extubation ( P = .04) and 90% received early feeding ( P < .001). The median intensive care unit and overall length of stay decreased from 2.5 to 1 days ( P = .005) and from 14.5 to 7.5 days ( P < .001), respectively. After final pathway implementation, there was no intensive care unit use (n=4). Postoperatively, no ERAS patient required escalation of care, and there was no difference in emergency department visits or readmissions., Conclusions: Applying ERAS principles to complete primary repair of bladder exstrophy was associated with decreased variations in care, improved patient outcomes, and effective resource utilization. Although ERAS has typically been utilized for high-volume procedures, our study highlights that an enhanced recovery pathway is both feasible and adaptable to less common urological surgeries.

Introduction: Judicious use of antibiotics for surgical prophylaxis is important for reducing antimicrobial resistance while preventing infectious surgical complications. In the setting of pediatric distal hypospadias repairs, it is unclear if antibiotic surgical prophylaxis is beneficial., Objective: The purpose of this study was to compare rates of infectious complications in pediatric subjects undergoing distal hypospadias repair who received any peri-operative antibiotics to those who did not., Study Design: This was a review of a retrospective cohort from a database of individuals undergoing hypospadias repairs evaluating whether they received peri-operative or post-operative antibiotic prophylaxis and determining the rate of infectious complications in those who did compared to those who did not receive antibiotic prophylaxis. Infectious complications were defined as surgical site infection (SSI) or urinary tract infection (UTI)., Results: There was no significant difference in infectious complication rates between individuals who received peri-operative parenteral antibiotic prophylaxis and those who did not. All subjects with infectious complications received post-operative oral antibiotic prophylaxis. There was one instance of C. difficile infection in a subject who received peri-operative parenteral antibiotics., Discussion: Reducing antibiotic utilization without increasing infectious surgical complications is important in safely reducing antimicrobial resistance. In this study of pediatric distal hypospadias repair, peri-operative antibiotics did not demonstrate a clear benefit and post-operative oral antibiotics demonstrated no benefit in preventing infectious complications. Other studies evaluating peri- and post-operative antibiotics for pediatric hypospadias repair have also failed to demonstrate a benefit for antibiotics in preventing infections. Practitioners should reconsider the use of antibiotics in this setting., Conclusion: Routine antibiotic prophylaxis does not appear beneficial for preventing infectious complications following uncomplicated, stented pediatric distal hypospadias repairs., Competing Interests: Conflicts of interest KMD owns stock in Merck and Organon&Co. Otherwise we have no conflicts of interest to disclose., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The thulium fiber laser is a promising new lithoptripsy technology never before studied in the pediatric population. Our center adopted the first platform in North America, the SuperPulsed thulium fiber laser (SPTF). We aimed to compare outcomes in pediatric ureteroscopy using the SPTF to those using the gold standard, low-power holmium:yttrium-aluminum-garnet (Ho:YAG) laser., Materials and Methods: This is a retrospective, consecutive cohort study of unilateral ureteroscopy with laser lithotripsy performed in pediatric patients from 2016 to 2021 as an early adopter of the SPTF. Thirty-day complications and stone-free status, defined as the absence of a stone fragment on followup imaging within 90 days, were analyzed using logistic regression. Operative times were compared using linear regression. Propensity scores for use of SPTF were used in regression analyses to account for potential cohort imbalance., Results: A total of 125 cases were performed in 109 pediatric patients: 93 with Ho:YAG and 32 with SPTF. No significant difference was noted in age (p=0.2), gender (p=0.6), stone burden (p >0.9) or stone location (p=0.1). The overall stone-free rate was 62%; 70% with SPTF and 59% with Ho:YAG. The odds of having a residual stone fragment were significantly lower with SPTF than with Ho:YAG (OR=0.39, 95% CI: 0.19-0.77, p=0.01). There was no significant difference in operative time (p=0.8). Seven (25%) complications were noted with SPTF and 19 (22%) with Ho:YAG (p=0.6)., Conclusions: The SPTF laser was associated with a higher stone-free rate than the low-power Ho:YAG laser without compromising operative time and safety.

Purpose: We performed a retrospective, single-institution study to characterize the pathological findings of testis tissue specimens from older boys and adolescents with cryptorchidism., Materials and Methods: With institutional review board approval, pathology reports were obtained for testicular specimens from patients age 10 years or older at a pediatric hospital from 1994 to 2016. Reports were excluded if they lacked clinical records, lacked testicular parenchyma, were from a descended testis or were from a patient with differences of sexual development. Variables of interest included age, testis location, procedure and pathological findings. Presence of malignancy among intra-abdominal versus extra-abdominal undescended testes was compared using Fisher's Exact Test., Results: Seventy-one patients met inclusion criteria. The median age was 15.3 years (range 10.1-27.7). None had a history of testicular malignancy. Forty-five unilateral orchiectomies, 22 unilateral orchiopexies with biopsy and 4 bilateral procedures were performed. Seventeen testes (22.7%) were intra-abdominal, 42 (56.0%) were in the inguinal canal, 9 (12.0%) were at the external inguinal ring, 3 (4.0%) were in the superficial inguinal pouch and 4 (5.3%) were in the scrotum. Malignancy was detected in 2/71 patients (2.8%). By location, 2/16 patients (12.5%) with intra-abdominal testis and 0/55 patients (0%) with extra-abdominal testis demonstrated malignancy (p=0.048)., Conclusions: Among males with cryptorchidism ages 10 years and older without differences of sexual development, 2/16 patients with intra-abdominal testis and 0/55 patients with extra-abdominal testis demonstrated malignancy. In older boys and adolescents, orchiectomy or biopsy is indicated for intra-abdominal testes but may not be necessary for extra-abdominal undescended testes.

Urologic chronic pelvic pain syndrome (UCPPS) is a condition of unknown etiology characterized by pelvic pain and urinary frequency and/or urgency. As the proximal fluid of this syndrome, urine is an ideal candidate sample matrix for an unbiased study of UCPPS. In this study, a large, discovery-phase, TMT-based quantitative urinary proteomics analysis of 244 participants was performed. The participants included patients with UCPPS (n = 82), healthy controls (HC) (n = 94), and disparate chronic pain diseases, termed positive controls (PC) (n = 68). Using training and testing cohorts, we identified and validated a small and distinct set of proteins that distinguished UCPPS from HC (n = 9) and UCPPS from PC (n = 3). The validated UCPPS: HC proteins were predominantly extracellular matrix/extracellular matrix modifying or immunomodulatory/host defense in nature. Significantly varying proteins in the UCPPS: HC comparison were overrepresented by the members of several dysregulated biological processes including decreased immune cell migration, decreased development of epithelial tissue, and increased bleeding. Comparison with the PC cohort enabled the evaluation of UCPPS-specific upstream regulators, contrasting UCPPS with other conditions that cause chronic pain. Specific to UCPPS were alterations in the predicted signaling of several upstream regulators, including alpha-catenin, interleukin-6, epidermal growth factor, and transforming growth factor beta 1, among others. These findings advance our knowledge of the etiology of UCPPS and inform potential future clinical translation into a diagnostic panel for UCPPS., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The initial imaging approach to children with urinary tract infection (UTI) is controversial. Along with renal/bladder ultrasound, some advocate voiding cystourethrogram (VCUG), ie a bottom-up approach, while others advocate dimercaptosuccinic acid (DMSA) scan, ie a top-down approach. Comparison of these approaches is challenging. In the RIVUR/CUTIE trials, however, all subjects underwent both VCUG and DMSA scan. Our objective was to perform a comparative effectiveness analysis of the bottom-up vs top-down approach., Materials and Methods: We simulated 1,000 hypothetical sets of 500 children using RIVUR/CUTIE data. In the top-down approach, patients underwent initial DMSA scan, and only those with renal scarring underwent VCUG. In the bottom-up approach, the initial study was VCUG. We assumed all children with vesicoureteral reflux (VUR) received continuous antibiotic prophylaxis (CAP). Outcomes included recurrent UTI, number of VCUGs and CAP exposure. We assumed a 25% VUR prevalence in children with initial UTI with sensitivity analysis using 40% VUR prevalence., Results: Median age of the original RIVUR/CUTIE cohort was 12 months. First DMSA scan was performed at a median of 8.2 weeks (IQR 5-11.8) after the index UTI. In the simulated cohort, slightly higher yet statistically significantly recurrent UTI was associated with the top-down compared with the bottom-up approach (24.4% vs 18.0%, p=0.045). On the other hand, the bottom-up approach resulted in more VCUG (100% vs 2.4%, p <0.001). Top-down resulted in fewer CAP-exposed patients (25% vs 0.4%, p <0.001) and lower overall CAP exposure (5 vs 162 days/person, p <0.001). Sensitivity analysis was performed with 40% VUR prevalence with similar results., Conclusions: The top-down approach was associated with slightly higher recurrent UTI. Compared to the bottom-up approach, it significantly reduced the need for VCUG and CAP.

Purpose: Recent studies have demonstrated trends of decreasing voiding cystourethrogram utilization rates and delayed vesicoureteral reflux diagnosis in some children. It is possible that such delays could lead to more children sustaining repeated episodes of febrile urinary tract infection, and potential kidney injury, prior to diagnosis and treatment., Materials and Methods: Using single institutional, cross-sectional cohorts of patients in 2 time periods (2005 and 2015), we compared clinical presentation and renal outcomes among patients 13 years and younger with history of febrile urinary tract infection presenting for initial voiding cystourethrogram. Outcomes included 1) recurrent urinary tract infection, 2) presence of vesicoureteral reflux, 3) grade of vesicoureteral reflux, and 4) renal scarring. Associations between year of presentation and outcomes of recurrent urinary tract infection and vesicoureteral reflux diagnosis were evaluated using multivariable logistic regression models. For the outcome of renal scarring, a logistic regression model was fitted for propensity score matched cohorts., Results: Compared to children presenting in 2005, those in 2015 had 3 times the odds of recurrent urinary tract infection (OR 3.01, 95% CI 2.18-4.16, p <0.0001). Time period was not associated with the odds of vesicoureteral reflux (OR 0.98, 95% CI 0.77-1.23, p=0.85). Those in 2015 were more likely to present with vesicoureteral reflux grade >3 (OR 2.22, 95% CI 1.13-4.34, p=0.02) but not vesicoureteral reflux grade >2 (OR 1.11, 95% CI 0.74-1.67, p=0.60). Renal scarring was more common among children presenting in 2015 (OR 2.9, 95% CI 1.03-8.20, p=0.04)., Conclusions: Compared to 2005, children presenting in 2015 for post-urinary tract infection voiding cystourethrogram have increased likelihood of recurrent urinary tract infection and renal scarring, despite similar likelihood of vesicoureteral reflux diagnosis.

Introduction/background: Bladder exstrophy patients have a high prevalence of inguinal hernia that often become clinically evident following bladder closure. Understanding when the bladder exstrophy patient is under greatest risk of developing an inguinal hernia following bladder closure is important, since incarceration resulting in strangulation of intra-abdominal contents can lead to significant morbidity if not addressed in a timely fashion. Although the incidence and risk factors of inguinal hernia have been reported, the timing of occurrence is not well understood., Objective: The primary objective of this study was to assess the timing of inguinal hernia following complete primary repair of bladder exstrophy (CPRE). In addition, we aimed to evaluate possible risk factors associated with inguinal hernia, including sex, age at bladder closure and iliac osteotomy status., Study Design: A multi-institutional retrospective review identified patients with bladder exstrophy repaired by CPRE under 6 months of age while excluding those who underwent inguinal hernia repair before or during bladder closure. Timing of inguinal hernia following bladder closure was evaluated using Kaplan-Meier methods. Cox proportional hazards model was used to investigate association of sex, age at bladder closure, and osteotomy on the risk of developing of inguinal hernia while clustering for institution., Results: 91 subjects were included in our analysis with median follow-up time of 6.5 years. 34 of 53 males (64.2%) and 2 of 38 females (5.3%) underwent inguinal hernia repair. The median time to inguinal hernia was 4.7 months following closure. The greatest hazard of inguinal hernia was within the first six months following closure. In multivariate analysis, male sex was strongly associated with inguinal hernia (HR = 19.00, p = 0.0038). Osteotomy and delay in closure were not significantly associated with inguinal hernia. 7 of 36 patients (19.4%) who underwent inguinal hernia repair presented with recurrence on the ipsilateral side., Discussion: Our results suggest that the greatest risk of inguinal hernia is within the first six months following bladder closure. The decreased risk of inguinal hernia after one year of follow-up may reflect anatomic stability that is reached following major reconstruction of the pelvis. While male bladder exstrophy patients are significantly more susceptible to inguinal hernias following CPRE, osteotomy and delayed bladder closure do not appear to be protective factors for inguinal hernia development following initial bladder closure., Conclusions: There is a heightened risk of inguinal hernia in the first six months following closure. The rate of recurrence following inguinal hernia repair is significantly elevated compared to the general pediatric population., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article to disclose., (Published by Elsevier Ltd.)

Background: During the COVID-19 crisis, there has been widespread reporting that non-COVID-19-related medical care has been delayed, even for emergent conditions. Testicular torsion is an emergent condition with higher risk of testicular loss with longer ischemic times. We sought to investigate whether patients with testicular torsion had longer time from symptom onset to initial presentation, longer total ischemic time, and higher rate of orchiectomy during the pandemic., Materials and Methods: Using billing data, we identified all patients age >1yo seen in our hospital from 1/1/2018 through 5/31/2020 who underwent emergent scrotal exploration for confirmed testicular torsion, comparing the COVID-19 crisis (3/1/2020-5/31/20) to the pre-COVID-19 period (1/1/2018-2/29/20). The primary outcome was time from symptom onset to initial presentation and secondary outcomes were ischemic time (time from symptom onset to entry of the OR) and orchiectomy rate. Parameters were compared with Mann-Whitney U and Fisher's exact tests; Poisson regression compared rates of torsion., Results: Of 94 total cases, 77 occurred during the pre-COVID-19 period and 17 during the COVID-19 crisis. Median time from symptom onset to initial presentation was not significantly different (2.4 h [IQR 1.1 h-38.9] during COVID-19 vs. 5.6 h [IQR 1.6-16.9] during pre-COVID-19 period, p = 0.476). Time to presentation was >12 h in 5/17 patients (29%) during COVID-19 and 24/77 patients (31%) during pre-COVID-19 period (p = 1.00). Median ischemic time during COVID-19 was 7.5 h (IQR 4.7 h-45.5 h) compared to 9.4 h (IQR 5.4 h-22.5 h) during pre-COVID-19 period (p = 0.694). Incidence of orchiectomy in our center was 29% (5/17) during COVID-19 and 17% (13/77) during pre-COVID-19 period (p = 0.397). About half of patients were seen initially at outside facilities prior to arrival (47% [8/17] during COVID-19 vs. 49% [38/77] during pre-COVID-19 period, p = 1.00). The number of torsion case presentations per week to our facility increased from 0.7 cases/week in the pre-COVID-19 period to 1.3 cases/week during COVID-19 (p = 0.015); when comparing only the March 1 to May 31 calendar period, there were 0.6 cases/week during the pre-COVID-19 period and 1.3 cases/week during COVID-19 (p = 0.021)., Conclusion: Time to presentation, ischemic times, and orchiectomy rates for testicular torsion at our center were not significantly different during the COVID-19 period compared to the preceding 2 year period. The number of torsion case per week presenting to our facility increased significantly., Competing Interests: Conflict of interest None., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction/background: The Nurse Practitioner (NP)-Led Newborn Circumcision Clinic (NCC), developed in 2016, provides clamp-style circumcision to newborns without general anesthesia. There is a paucity of research regarding outcomes, satisfaction, and the cost benefit of such NP-led clinics., Objective: The purpose of this descriptive study was to describe the impact of the NCC including family satisfaction, clinical and demographic characteristics, and cost., Study Design: This study utilized a mixed-method approach to describe the impact of the NP-led NCC using survey methodology to describe family satisfaction, a single center retrospective chart review to describe clinical and demographic characteristics and outcomes, and investigation of charges in NCC versus operating room (OR) circumcisions. Descriptive statistics were used to present survey results and chart review data., Results: Results of the patient satisfaction survey revealed 89.8% of patients rated the overall quality of care as excellent or very good. Of the 234 patients reviewed, the median age and weight of patients was 4.30 weeks and 4.39 kg, respectively. Of the patients with comorbidities (30.3%), the most common were related to prematurity (12.8%). The most common reason for referral was concern for anatomical abnormality of the penis (53.8%). The median length of procedure was 20 minutes. No patients in our cohort experienced penile amputations, infections, strictures, intraoperative bleeding, or wounds. Ten patients (4.3%) had bleeding events during the recovery period which were treated with a topical medication (StatSeal). Two patients (0.9%) had bleeding after discharge requiring Emergency Department evaluation and application of a pressure dressing. Two patients (0.9%) required circumcision revision. Investigation of charges revealed a savings of 92.9% for circumcisions in the NCC versus OR., Discussion: This study reveals that the NP-led NCC has high family satisfaction, few adverse outcomes, and cost benefits as compared to OR circumcision. There are a limited number of publications presenting outcome data for circumcisions and even fewer for NP- led circumcision clinics. Furthermore, a lack of standardized definitions for adverse events makes comparison difficult., Conclusions: Critical to the success of the NP-led NCC is appropriately selecting patients, a NP training program, and intra-professional collaboration. This ambulatory clinic offers another option for select infants who were not immediately circumcised in the newborn period. By expanding opportunities for NPs to practice to the full extent of their education and expertise, our institution continues to develop opportunities to improve access to care, control costs, and increase patient and family satisfaction., Competing Interests: Conflicts of interest All authors have no conflicts of interest to disclose., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the accuracy of renal ultrasound (RUS) in detecting renal scarring (RS)., Methods: All initial DMSA scans performed from 2006 to 2009 for history of urinary tract infection (UTI) or vesicoureteral reflux (VUR) in patients under 14 years old were identified, and clinical history obtained via chart review. Patients who had RUS within 4 months of DMSA scan and no documented UTI during that interval were included. Decreased uptake of tracer associated with loss of contours or cortical thinning defined a positive DMSA study. Increased echogenicity/dysplasia, cortical thinning, atrophic kidney and/or abnormal corticomedullary differentiation defined a positive RUS. The sensitivity and specificity of RUS in identifying RS were calculated using DMSA scan as the gold standard., Results: A total of 144 patients had initial DMSA scans performed for UTI or VUR, with a RUS within 4 months, and no UTI between the 2 studies. Ninety-five of 144 (66%) had RS on DMSA and 49/144 (34%) did not. Patients with or without RS on DMSA were not different in gender (P = .073), age (P = .432), insurance (P = 1.000) or VUR grade (P = .132). Only 39/144 (27.1%) patients had positive RUS. The sensitivity of RUS for RS was 35.8% and the specificity was 89.8%, leading to an accuracy of 54.2% (95%CI; 45.7-62.5%, P = .999)., Conclusion: RUS demonstrated poor sensitivity for RS visualized on DMSA scan. This suggests that RUS is a poor screening test for RS or indicators of future renal scar. A normal ultrasound does not rule out RS or risk of future renal scar. Specificity of RUS was excellent., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The consensus classification system for urinary tract dilatation (UTD) was designed to be more objective and reproducible than previously used systems. We sought to evaluate interobserver reliability of UTD components and overall scores in a prenatal population undergoing third-trimester ultrasound examinations., Methods: We retrospectively identified patients who underwent antenatal ultrasound examinations for UTD between 28 and 40 weeks' gestation. All images from individual studies of 300 fetuses were reviewed independently by 5 experienced sonologists (1 maternal-fetal medicine specialist and 4 radiologists). Urinary tract dilatation scores (normal, A1, or A2/3) and Society for Fetal Urology (SFU) scores were assigned. Interobserver agreement between raters was evaluated with the Fleiss κ statistic., Results: Overall interobserver agreement for the antenatal UTD risk score showed substantial agreement among all 5 readers (κ = 0.657 [95% confidence interval, 0.632, 0.683]; P < .001). All 5 readers applied the same UTD risk score in 53.7% of cases. Some variability in the antenatal UTD score and individual elements was observed. At least 2 UTD risk scores were assigned to a specific individual patient in 46.3% of cases (139 of 300), and all 3 UTD risk scores were assigned to a specific individual patient in 1.7% of cases (5 of 300). In 18.0% of cases (54 of 300), at least 2 readers assigned a UTD score different from that assigned by the other readers. Agreement was lowest for parenchymal appearance (κ = 0.225). Agreement for the SFU system was fair (κ = 0.368; P < .001)., Conclusions: Interobserver agreement for the antenatal UTD grading system was substantial. Compared to the SFU system, the antenatal UTD system showed better agreement among readers., (© 2019 by the American Institute of Ultrasound in Medicine.)

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort., (© 2020 Vitko et al.)

Purpose: The RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial reported that antibiotic prophylaxis reduced recurrent urinary tract infection but antibiotic prophylaxis was not associated with decreased new renal scarring. However, the original reports did not assess the relationship among recurrent urinary tract infection, new renal scarring and antibiotic prophylaxis in detail. Therefore, we investigated the relationship among these issues., Materials and Methods: We included subjects with dimercaptosuccinic acid scan within 6 months of enrollment and at least 1 followup dimercaptosuccinic acid scan from the RIVUR trial. The primary outcome was recurrent urinary tract infection associated new renal scarring, defined as recurrent urinary tract infection and new changes on dimercaptosuccinic acid scan. Due to a low number of events, propensity score was used to adjust for confounders. Multivariate logistic regression was fitted to investigate the associations between the covariates and the outcome., Results: A total of 489 patients (91% female, mean age 20.3 months) were included in the study. Any new renal scarring was more common among those with recurrent urinary tract infection (OR 4.1, 95% CI 2.0-8.5, p <0.01) after adjusting for age, sex, index urinary tract infection, duplication, bowel bladder dysfunction and antibiotic prophylaxis. Recurrent urinary tract infection associated new renal scarring occurred in 5 of 244 (2%) patients on antibiotic prophylaxis and 13 of 245 (5%) on placebo. Compared to antibiotic prophylaxis, placebo was associated with a higher risk of recurrent urinary tract infection associated new renal scarring (OR 3.1, 95% CI 1.0-8.8, p=0.04) after adjusting for age, sex, race, index urinary tract infection, bowel bladder dysfunction, duplication, hydronephrosis, vesicoureteral reflux grade and baseline renal scarring. There were no differences in scar severity at final dimercaptosuccinic acid scan (p=0.88) or change from baseline (p=0.53) between antibiotic prophylaxis and placebo., Conclusions: Recurrent urinary tract infection was associated with new renal scarring in the RIVUR trial. When limited to recurrent urinary tract infection associated new renal scarring, antibiotic prophylaxis was associated with a decreased risk of this outcome. It remains unclear why new renal scarring developed in a proportion of subjects without recurrent urinary tract infection. The results should be carefully interpreted due to the inherent limitations.

Purpose: The Urinary Tract Dilation classification system was designed to be more objective and reproducible than currently available grading systems. We evaluated the reliability and consistency of the system in newborns., Materials and Methods: Of 1,046 infants 0 to 90 days old undergoing ultrasound for hydronephrosis 243 were randomly selected for study inclusion. Seven readers (4 radiologists and 3 urologists) at 4 institutions classified complete, de-identified ultrasound studies on a Web based platform. Interobserver and intra-observer agreement was evaluated using the Fleiss kappa statistic., Results: Interobserver agreement for Urinary Tract Dilation risk score was moderate among the 7 readers (kappa = 0.421, 95% CI 0.404-0.438). Interobserver agreement using the Society for Fetal Urology scale was worse than with the Urinary Tract Dilation classification (kappa = 0.344, 95% CI 0.330-0.359). All 7 readers assigned the same Urinary Tract Dilation score in 19.3% of cases (47 of 243). In 38.7% of cases (94 of 243) at least 3 readers assigned a Urinary Tract Dilation score different from that assigned by the other readers. In 7% of cases (17 of 243) at least 3 readers assigned a score of P0/P1, while at least 3 readers scored the same cases as P2/P3. At least 3 different Urinary Tract Dilation risk scores were assigned to the same patient in 30.45% of patients (74 of 243). Among individual Urinary Tract Dilation elements calyceal dilatation and bladder status had the highest disagreement. Five readers regraded 80 cases and agreed with their previous Urinary Tract Dilation risk score in 63.8% to 75.0% of cases (kappa 0.458 to 0.729)., Conclusions: Interobserver agreement using the Urinary Tract Dilation grading system is fair to moderate, with variable agreement on individual elements of the system. Agreement was higher for the Urinary Tract Dilation system compared to the Society for Fetal Urology scale.

Background: Fluoroscopy is commonly used during pediatric ureteroscopy (PURS) for urolithiasis, and the most important contributor to overall radiation exposure is fluoroscopy time (FT). One factor that may impact FT is who controls activation of the fluoroscope: the urologist (with a foot pedal) or the radiation technologist (as directed by the urologist). While there are plausible reasons to believe that either approach may lead to reduced FT, there are no systematic investigations of this question. We sought to compare FT with surgeon-control versus technologist control during PURS for urolithiasis., Methods: We conducted a randomized controlled trial (Clinicaltrials.gov ID number: NCT02224287). Institutional Review Board approval was sought and obtained for this study. All subjects (or their legal guardians) provided informed consent. Each patient (age 5-26 years) was randomized to surgeon- or technologist-controlled fluoroscope activation. Block randomization was stratified by the surgeon. For technologist control, the surgeon verbally directed the technologist to activate the fluoroscope. For surgeon control, a foot pedal was used by the surgeon. The technologist controlled c-arm positioning, settings, and movement. The primary outcome was total FT for the procedure. Secondary outcomes included radiation exposure (entrance surface air kerma [ESAK] mGy). We also analyzed clinical and procedural predictors of FT and exposure. Mixed linear models accounting for clustering by surgeon were developed., Results: Seventy-three procedures (5 surgeons) were included. The number of procedures per surgeon ranged from seven to 36. Forty-three percent were pre-stented. Thirty-one procedures were left side, 35 were right side, and seven were bilateral. Stones were treated in 71% of procedures (21% laser, 14% basket, and 65% laser/basket). Stone locations were distal ureter (11.5%), proximal/mid-ureter (8%), renal (69%), and ureteral/renal (11.5%). An access sheath was used in 77%. Median stone size was 8.0 mm (range 2.0-20.0). Median FT in the surgeon control group was 0.5 min (range 0.01-6.10) versus 0.55 min (range 0.10-5.50) in the technologist-control group (p = 0.284). Median ESAK in the surgeon control group was 46.02 mGy (range 5.44-3236.80) versus 46.99 mGy (range: 0.17-1039.31) in the technologist-control group (p = 0.362). Other factors associated with lower FT on univariate analysis included female sex (p = 0.015), no prior urologic surgeries (p = 0.041), shorter surgery (p = 0.011), and no access sheath (p = 0.006). On multivariable analysis only female sex (p = 0.017) and no access sheath (p = 0.049) remained significant. There was significant variation among surgeons (p < 0.0001); individual surgeon median FT ranged from 0.40 to 2.95 min., Conclusions: Fluoroscopy time and radiation exposure are similar whether the surgeon or technologist controls fluoroscope activation. Other strategies to reduce exposure might focus on surgeon-specific factors, given the significant variation between surgeons., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Urethral meatotomy as treatment for meatal stenosis is a common pediatric urology procedure; however, little is known about the patient experience following this procedure., Objective: We aim to evaluate clinical factors associated with patient-reported symptom improvement after urethral meatotomy., Study Design: The families of boys undergoing urethral meatotomy between 2/2013 and 8/2016 received a survey by mail 6 weeks after surgery. Families were queried on changes in symptoms using a Likert-type scale (5 = much improved, 4 = somewhat improved, 3 = no change, 2 = somewhat worse, and 1 = much worse). Patient and procedure characteristics of the respondents were obtained via chart review. These included surgical indication(s) (abnormal stream, dysuria, or storage symptoms), postoperative complications, reoperation, and unplanned postoperative communications. Patients who had procedures other than simple urethral meatotomy were excluded. Descriptive statistics were compiled, and generalized estimating equations used to determine the associations of patient and procedure characteristics with symptom improvement., Results: We sent 629 surveys and received 194 responses (30.4%). Twelve respondents were excluded for complex procedures or miscoding. The majority of respondents were privately insured (74%) and were between 5 and 12 years old (45%) or 1 and 4 years old (42%). The most frequent surgical indication was abnormal stream (72%) followed by pain (21%) and storage symptoms (15.5%). Nine respondents had minor complications (4.9%). Four patients had restenosis requiring repeat urethral meatotomy. After surgery, a majority (79%) were "much improved," 16% were "somewhat improved," 3% had "no change," and 1% were "somewhat worse." No family reported "much worse." Those patients who had "abnormal stream" as a surgical indication were significantly more likely to report "much improved" (OR 1.83, p = 0.014) than those without. Patient-reported improvement was not associated with suture use, patient age, insurance, surgeon, or location of the procedure (Table)., Discussion: Little has been written about patient-reported outcomes following urethral meatotomy. Our study affirms that the majority of boys improve following this procedure. However, improvement is significantly more likely if the child has a preoperative indication of an abnormal stream, such as deflection or spraying. Boys with symptoms of dysuria, frequency, or incontinence may be experiencing sequelae of meatal stenosis that simply take longer to improve. Alternatively, the meatal stenosis may be incidental to the primary symptoms., Conclusions: A majority of families report substantial symptomatic improvement after urethral meatotomy. However, boys undergoing urethral meatotomy for reasons other than a urinary stream abnormality are less likely to experience improvement., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The bladder urothelium functions as a urine-blood barrier and consists of basal, intermediate, and superficial cell populations. Reconstructive procedures such as augmentation cystoplasty and focal mucosal resection involve localized surgical damage to the bladder wall whereby focal segments of the urothelium and underlying submucosa are respectively removed or replaced and regeneration ensues. We demonstrate using lineage-tracing systems that urothelial regeneration following augmentation cystoplasty with acellular grafts exclusively depends on host keratin 5-expressing basal cells to repopulate all lineages of the de novo urothelium at implant sites. Conversely, repair of focal mucosal defects not only employs this mechanism, but in parallel host intermediate cell daughters expressing uroplakin 2 give rise to themselves and are also contributors to superficial cells in neotissues. These results highlight the diversity of urothelial regenerative responses to surgical injury and may lead to advancements in bladder tissue engineering approaches., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Usage of online resources by clinicians in training and practice can provide insight into knowledge gaps and inform development of decision support tools. Although online information seeking is often driven by encountered patient problems, the relationship between disease prevalence and search rate has not been previously characterized. Objective This article aimed to (1) identify topics frequently searched by pediatric clinicians using UpToDate (http://www.uptodate.com) and (2) explore the association between disease prevalence rate and search rate using data from the Pediatric Health Information System. Methods We identified the most common search queries and resources most frequently accessed on UpToDate for a cohort of 18 children's hospitals during calendar year 2012. We selected 64 of the most frequently searched diseases and matched ICD-9 data from the PHIS database during the same time period. Using linear regression, we explored the relationship between clinician query rate and disease prevalence rate. Results The hospital cohort submitted 1,228,138 search queries across 592,454 sessions. The majority of search sessions focused on a single search topic. We identified no consistent overall association between disease prevalence and search rates. Diseases where search rate was substantially higher than prevalence rate were often infectious or immune/rheumatologic conditions, involved potentially complex diagnosis or management, and carried risk of significant morbidity or mortality. None of the examined diseases showed a decrease in search rate associated with increased disease prevalence rates. Conclusion This is one of the first medical learning needs assessments to use large-scale, multisite data to identify topics of interest to pediatric clinicians, and to examine the relationship between disease prevalence and search rate for a set of pediatric diseases. Overall, disease search rate did not appear to be associated with hospital disease prevalence rates based on ICD-9 codes. However, some diseases were consistently searched at a higher rate than their prevalence rate; many of these diseases shared common features., Competing Interests: Conflict of Interest: None.

Background: Renal and bladder ultrasound (RBUS) is recommended in evaluation of children after an initial, febrile urinary tract infection. Although it is not uncommon to observe debris within the bladder lumen on sonography, the significance of this finding is uncertain. Debris may be interpreted as an indication of ongoing infection, but there have been no studies to date investigating the association of bladder debris with a positive culture., Objective: The aim of this study was to evaluate the association of bladder debris noted at the time of RBUS with positive urine culture results obtained from a catheterized specimen, among patients undergoing RBUS and voiding cystourethrogram (VCUG) on the same day., Study Design: We performed a retrospective cross-sectional study of 3995 patients who presented for same-day RBUS and VCUG. RBUS reports were reviewed for the presence of bladder debris, and analysis was limited to patients under 60 months of age with a catheterized urine specimen sent for culture at the time of the studies. Those with prior postnatal imaging or a diagnosis of prenatal hydronephrosis or other GU abnormalities were excluded. Thirty-four subjects with bladder debris on RBUS were identified and matched to 155 controls based on age, gender, circumcision status, and presence of vesicoureteral reflux. A positive urine culture was defined as ≥50,000 colony forming units per mL of at least one organism. A conditional logistic regression model was used to evaluate the association between debris on RBUS and positive urine culture results., Results: In conditional logistic regression stratifying by matching age, gender, circumcision status, and presence of vesicoureteral reflux, there was a statistically significant association between bladder debris on RBUS and positive urine culture result collected on the same day during VCUG (OR 7.88, 95% CI 1.88-33.04, p = 0.0048). This corresponds to a 688% increase in odds of positive urine culture for patients with debris (Table)., Discussion: This is the first study to evaluate the association between bladder debris on RBUS and positive urine culture, and it should serve as a starting point for future investigations. The study is limited in its generalizability to the sampled population; further work should evaluate the predictive value of RBUS debris among children without UTI history, with prior imaging or known genitourinary anomalies, or older children., Conclusion: Among children younger than 60 months old undergoing initial imaging for history of UTI, there is a significant association between bladder debris and a positive urine culture., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions., Objective: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients., Methods: Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily., Results: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses., Conclusion: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease.

Objective: To examine trends in the number of cases of primary vesicoureteral reflux managed by ureteral reimplantation nationally over the last decade. Substantial changes have occurred in management of vesicoureteral reflux (VUR) over time, but trends in use of ureteral reimplantation have yet to be investigated on a national scale with annualized data., Materials and Methods: Using the Premier Healthcare Database, we extracted hospital discharge data for pediatric patients (age ≤ 18 years) with a procedure code for ureteroneocystostomy (International Classification of Diseases, Ninth Revision, 56.74) between January 1, 2003 and December 31, 2013. We excluded patients with secondary VUR. The presence of a temporal trend in reimplantation was examined via regression using generalized estimating equations., Results: In 4301 cases of primary VUR (23,602 weighted), there was a substantial decrease in the number of reimplantations performed, with an estimated decline in the rate of 0.239 cases per attending per year (P = .006). Average patient age declined 1.2 months in each year (P < .0001) due largely to a decline in reimplantation in those over age 2, which fell by 0.15 reimplantations per attending per year (P = .026). There was no difference between rates of decline in reimplantation for children with and without reflux nephropathy (P = .21) CONCLUSION: Nationally there has been a marked decrease in the incidence of ureteral reimplantation among children with primary VUR. The potential factors contributing to this are broad, including changes in diagnostic patterns, treatment recommendations, and the rise of endoscopic intervention., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: We sought to compare complications and direct costs for open ureteral reimplantation (OUR) versus robot-assisted laparoscopic ureteral reimplantation (RALUR) in a sample of hospitals performing both procedures. Anecdotal reports suggest that use of RALUR is increasing, but little is known of the outcomes and costs nationwide., Objective: The aim was to determine the costs and 90-day complications (of any Clavien grade) in a nationwide cohort of pediatric patients undergoing OUR or RALUR., Methods: Using the Premier Hospital Database we identified pediatric patients (age < 21 years) who underwent ureteral reimplantation from 2003 to 2013. We compared 90-day complication rates and cost data for RALUR versus OUR using descriptive statistics and hierarchical models., Results: We identified 17 hospitals in which both RALUR and OURs were performed, resulting in a cohort of 1494 OUR and 108 RALUR cases. The median operative time was 232 min for RALUR vs. 180 min for OUR (p = 0.0041). Incidence of any 90-day complications was higher in the RALUR group: 13.0% of RALUR vs. 4.5% of OUR (OR = 3.17, 95% CI: 1.46-6.91, p = 0.0037). The difference remained significant in a multivariate model accounting for clustering among hospitals and surgeons (OR, 3.14; 95% CI, 1.46-6.75; p = 0.0033) (Figure). The median hospital cost for OUR was $7273 versus $9128 for RALUR (p = 0.0499), and the difference persisted in multivariate analysis (p = 0.0043). Fifty-one percent (55/108) of the RALUR cases occurred in 2012-2013., Discussion: We present the first nationwide sample comparing RALUR and OUR in the pediatric population. There is currently wide variation in the probability of complication reported in the literature. Some variability may be due to differential uptake and experience among centers as they integrate a new procedure into their practice, while some may be due to reporting bias. A strength of the current study is that cost and 90-day postoperative complication data are collected at participating hospitals irrespective of outcomes, providing some immunity from the reporting bias to which individual center surgical series' may be susceptible., Conclusions: Compared with OUR, RALUR was associated with a significantly higher rate of complications as well as higher direct costs even when adjusted for demographic and regional factors. These findings suggest that RALUR should be implemented with caution, particularly at sites with limited robotic experience, and that outcomes for these procedures should be carefully and systematically tracked., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the mean and normal range of anteroposterior diameter (APD) of the renal pelves in children., Methods: Patients aged 0-19 years with normal spinal MRIs were identified after institutional review board approval. Those with dilating uropathy or abdominal surgery/radiation were excluded. The maximum APD was measured. A mixed linear model was fit to determine the relationship between APD and age, adjusted for bladder distention. The left and right kidneys were treated independently., Results: 283 left and 285 right renal units were included. For the left, a 3.5% increase in APD per year was predicted (p < 0.0001), with the average APD for infants and 18-year olds with non-distended bladders being 2.5 mm (95th percentile: 7.2 mm) and 4.6 mm (13.4 mm), respectively. For the right, a 3.9% increase in APD per year was predicted (p < 0.0001), with the average APD for infants and 18-year olds with non-distended bladders being 2.8 mm (8.4 mm) and 5.5 mm (16.6 mm), respectively. Compared with a non-distended bladder, a distended bladder increased the predicted APD between 23% (right) and 38% (left) (p = 0.01 and p < 0.0001, respectively)., Conclusion: The mean and normal ranges of APD measured by MRI in children are provided. APD increases with age and bladder distension and is greater on the left. Advances in knowledge: This article establishes normative ranges for APD, a critical component of genitourinary tract evaluation, and does so using the most precise imaging modality for this condition.

Background: Siblings of children with vesicoureteral reflux (VUR) are at elevated risk of VUR. Screening siblings may identify VUR before a clinical illness such as a urinary tract infection (UTI), but the benefit of screening has not been demonstrated. We sought to determine the incidence of UTI among siblings, and we hypothesized that the sibling UTI rate is similar between screened and unscreened siblings., Methods: We performed a retrospective cohort analysis using insurance claims data (January 1, 2000, to December 31, 2009). Within each family, we identified the index VUR patient and siblings; we included siblings who were enrolled in the insurance plan from birth for at least 1 year. We identified siblings who were screened for VUR and/or had UTI. We investigated the association of screening and UTI, controlling for patient characteristics and clustering within families., Results: Among 617 siblings (associated with 497 index patients), 317 (51%) were girls. Median insurance enrollment time was 53.0 months, with 424 enrolled ≥3 years. Among those with 1 or 3 years of enrollment, the proportions of siblings who experienced UTI was 8.4% (52 of 617) and 10.4% (44 of 424), respectively. Median age at initial UTI was 32.7 months. A total of 223 siblings (36.0%) underwent sibling screening. There was no significant difference in UTI between screened and unscreened siblings (odds ratio 1.57, 95% confidence interval 0.87-2.85; P = .14). In multivariate analysis, screening was not associated with sibling UTI incidence (odds ratio 1.33, 95% confidence interval 0.68-2.60; P = .40)., Conclusions: Although UTI is relatively common among siblings of VUR patients, there was no statistically significant difference in UTI incidence between screened and unscreened siblings., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)