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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.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.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, p0.0001). 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 grade3 (OR 2.22, 95% CI 1.13-4.34, p=0.02) but not vesicoureteral reflux grade2 (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).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.

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.

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

We performed a retrospective, single-institution study to characterize the pathological findings of testis tissue specimens from older boys and adolescents with cryptorchidism.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.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).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.

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.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.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%, p0.001). Top-down resulted in fewer CAP-exposed patients (25% vs 0.4%, p0.001) and lower overall CAP exposure (5 vs 162 days/person, p0.001). Sensitivity analysis was performed with 40% VUR prevalence with similar results.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.

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

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...

Summary 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. Summary Table 1 . Comparison of patients, timing, and testicular outcomes among patients with testicular torsion before and during COVID-19 crisis. Overall Pre-COVID COVID p-value n 94 77 17 Age, years (median [IQR]{range}) 14.38 [12.70, 15.87] {1.3–19.7} 14.22 [12.64, 15.83]{1.3–19.7} 15.24 [14.21, 16.01]{4.2–17.4} 0.2950 Time from symptom onset to presentation, hours (median [IQR]{range}) 5.38 [1.49, 18.38]{0.7, 148.0} 5.58 [1.60, 16.85]{0.7, 81.3} 2.40 [1.12, 38.92]{0.9, 148.0} 0.4760 Time from symptom onset to presentation > 6 h, n (%) 43 (45.7) 35 (45.5) 8 (47.1) 1.0000 Time from symptom onset to presentation > 12 h, n (%) 29 (30.9) 24 (31.2) 5 (29.4) 1.0000 Ischemic time, hours (Time from symptom onset to OR) (median [IQR]{range}) 9.19 [5.32, 26.02]{2.7, 152.2} 9.40 [5.42, 22.52]{2.7, 86.3} 7.52 [4.67, 45.45]{2.7, 152.2} 0.6940 Orchiectomy, n (%) 18 (19.1) 13 (16.9) 5 (29.4) 0.3970 Presentation at OSH, n (%) 46 (48.9) 38 (49.4) 8 (47.1) 1.0000

Summary 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. Summary Table . NP-led Newborn Circumcision Clinic Clinical Outcomes NCC Clinical Outcomes Median [IQR]/n (%) During Circumcision Procedure N = 234 Length of Procedure Events that Occurred 20.00 min [13.00 - 28.00] Sutures by MD for Skin Separation 2 (0.9) None 232 (99.1) During Recovery Length of Recovery Events that Occurred 60.00 min [60.00 - 60.00] Bleeding Treated by StatSeal Topically 10 (4.3) None 224 (95.7) Post-procedural Day 0 to Day 6 Events that Occurred Unplanned Emergency Department Visit for Bleeding 2 (0.9) Treated with Pressure Dressing 2 (100) None 232 (99.1) Follow-up Visit: Post-procedural Day 7 N = 228 Events that Occurred Adhesions 10 (4.4) Treated with Betamethasone Topically 9 (90.0) Noted without Treatment 1 (10.0) None 218 (95.6) After Follow-up Visit Unplanned Clinic Visit Adhesions 7 (3.1) Treated with Betamethasone Topically 2 (28.6) In-Office Lysis of Adhesions 5 (71.4) Parental Concern/Normal Anatomy 1 (0.4) Cicatrix Treated with Betamethasone 2 (0.9) Circumcision Revision 2 (0.9)

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.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.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.

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.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.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, p0.01) 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.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.

There are limited data on the predictive value of the consensus urinary tract dilation (UTD) score with respect to subsequent clinical diagnoses. We sought to define the relationship between postnatal UTD risk score and clinical outcomes during childhood.Complete ultrasound image sets from a random selection of infants aged 0-90 days undergoing initial ultrasound at a single institution for prenatal hydronephrosis between 2012 and 2014 were assigned a UTD score by 1 pediatric urologist and 1 pediatric radiologist. Urinary tract dilation risk score was analyzed for association with a composite outcome comprising urinary tract infection, vesicoureteral reflux (VUR), ureteropelvic junction obstruction, non-refluxing megaureter (NRM), ureterocele, bladder outlet obstruction (BOO), and chronic kidney disease. Surgical intervention and resolution of UTD were evaluated separately. Descriptive and survival analyses were performed.Urinary tract dilation scores for 494 subjects were P0 in 23.5%, P1 in 26.5%, P2 in 23.5%, and P3 in 26.5%. Seventy-four percent were male. Median age at initial imaging was 28 days; median follow-up was 19.8 months. The composite outcome occurred in 138 of 494 patients (27.9%) and varied significantly (p 0.001) by UTD score: 11.2% for P0, 10.7% for P1, 29.3% for P2, and 58.8% for P3. On survival analysis (Summary Figure), higher UTD grade was significantly associated with the composite outcome (hazard ratio for P3 vs. P0 was 7.4 [95% CI: 3.44-15.92, p 0.001]). Urinary tract infection and VUR diagnosis varied by UTD score (p = 0.03 and p 0.001, respectively). Ureteropelvic junction obstruction was diagnosed (based on MAG3 results) in 6.3% of patients, 84% of whom were P3. Non-refluxing megaureter was diagnosed in 7.7%. Ureterocele and BOO were uncommon (1.4%, and 0.6%, respectively). Surgical intervention was also associated with UTD risk, with 46% of P3 undergoing surgery vs. 1% of P0, 1% of P1, and 6% of P2 (p 0.001). Resolution of UTD occurred in 41% (median 10.1 months) and varied significantly by UTD risk (p 0.001).Urinary tract dilation risk score is associated with clinical events, although ascertainment bias may influence some of the differences in outcomes, particularly for VUR, because VCUG utilization varied by the UTD group. The lack of any significant difference in outcomes between patients with UTD P0 versus P1 suggests that the P1 category could be eliminated as it does not meaningfully distinguish between outcome risk.Higher UTD risk scores are strongly associated with genitourinary diagnoses during the first two years of life.

Summary 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. Download : Download high-res image (250KB) Download : Download full-size image Summary Figure . Kaplan–Meier curves for overall probability of inguinal hernia repair for males and females

INTRODUCTION: There is a lack of consensus regarding the use of continuous antibiotic prophylaxis (CAP) during the interval between birth and initial postnatal imaging in infants with a history of antenatal urinary tract dilation (AUTD). OBJECTIVE: To determine the incidence of urinary tract infection (UTI), and the association between CAP use and UTI during the interval between birth and the first postnatal renal ultrasound (RUS) in infants with AUTD. STUDY DESIGN: A single-institution, retrospective cohort study of newborns with a history of AUTD. Infants undergoing RUS within 3 months of birth for an indication of ‘hydronephrosis’ between 2012 and 2014 were identified. A random sample of 500 infants was selected; six were excluded for concomitant congenital anomalies. Baseline patient (sex, race, insurance) and clinical characteristics (circumcision status, UTD risk score, receipt of CAP, UTI prior to RUS, age at UTI, and age at RUS) were collected via retrospective chart review. Descriptive statistics were calculated. To adjust for receipt of CAP, propensity score adjusted univariate logistic regression for UTI based on CAP status was performed. RESULTS: Among the 494 infants with AUTD, 157 (32%) received CAP. Infants with normal/low-risk UTD scores were less likely to receive CAP than those with medium/high-risk UTD (23% vs 77%; P

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.

Summary 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., Highlights • The pattern of urothelial regeneration is dictated by the mode of surgical injury • Urothelial repair at bladder augment sites is dependent on host basal cell progeny • Repair of mucosal defects involves host basal and intermediate cell progeny, In this article, Mauney and colleagues show the source of urothelial progenitors utilized during bladder regeneration is dependent on the nature of injury. Fate-mapping experiments reveal that host basal and intermediate cell progeny differentially contribute to de novo urothelial formation in bladder augmentation and mucosal resection settings. These results highlight the diversity of urothelial regenerative responses to surgical injury.

Objectives/Hypothesis To characterize the frequency and nature of readmissions to free standing pediatric hospitals after otolaryngologic procedures. Study Design Retrospective national database analysis. Methods Using the Pediatric Health Information Systems database, we examined 30-day inpatient readmissions in children less than 18 years old who underwent otolaryngology procedures between January 1, 2009, and December 31, 2011. Univariate and multivariate logistic regression analyses accounting for correlated structure of the data identified factors related to readmission rate. Reasons for readmission and the postoperative day at which readmission occurred were also examined. Results In the 24-month study period, a total of 493,507 procedures were performed, resulting in 11,574 (2.3%) 30-day readmissions. Readmission rates varied significantly based on the type of procedure, patient age, and presence of chronic medical condition(s). Direct surgical complications accounted for 3,432 (29.7%) of all readmissions; and 4,729 (40.9%) of all readmissions occurred following tonsil and adenoid surgery. Conclusion Readmissions after pediatric otolaryngologic surgery are relatively uncommon. These readmission rates vary directly with the type of procedure performed, as well as patient level factors (i.e., patient age, ethnicity, and the presence of other medical comorbidities). These data demonstrate that if readmission rates are to be used as a quality measure in pediatric otolaryngology procedures, complex risk adjustment of patient level variables will be necessary to accurately compare outcomes between different hospitals. Level of Evidence 2c. Laryngoscope, 2015

There are few guidelines and little data on imaging after urinary tract infections in older children. We determined the clinical yield of renal and bladder ultrasound, and voiding cystourethrogram in older children and adolescents after urinary tract infection.We analyzed findings on voiding cystourethrogram, and renal and bladder ultrasound as well as the clinical history of patients who underwent the 2 studies on the same day between January 2006 and December 2010. We selected for study patients 5 to 18 years old who underwent imaging for urinary tract infection. Those with prior postnatal genitourinary imaging or prenatal hydronephrosis were excluded from analysis.We identified a cohort of 153 patients, of whom 74% were 5 to 8 years old, 21% were 8 to 12 years old and 5% were 12 to 18 years old. Of the patients 77% were female, 78% had a febrile urinary tract infection history and 55% had a history of recurrent urinary tract infections. Renal and bladder ultrasound findings revealed hydronephrosis in 7.8% of patients, ureteral dilatation in 3.9%, renal parenchymal findings in 20% and bladder findings in 12%. No patient had moderate or greater hydronephrosis. Voiding cystourethrogram showed vesicoureteral reflux in 34% of cases and bladder or urethral anomalies in 12%. Reflux was grade I, II-III and greater than III in 5.9%, 26% and 2% of patients, respectively. For any voiding cystourethrogram abnormality the sensitivity and specificity of any renal and bladder ultrasound abnormality were 0.49 (95% CI 0.37-0.62) and 0.76 (95% CI 0.66-0.84), respectively. Positive and negative predictive values were 0.58 (95% CI 0.44-0.71) and 0.69 (0.59-0.77), respectively.In older children with a history of urinary tract infection the imaging yield is significant. However, imaging revealed high grade hydronephrosis or high grade vesicoureteral reflux in few patients. Renal ultrasound is not reliable for predicting voiding cystourethrogram findings such as vesicoureteral reflux.

Summary 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. Table . Patient characteristics and key outcomes stratified by patient-reported improvement. Not “much improved” “Much improved” p-value (n = 38) (n = 144) Patient characteristics Indication (n; %) Stream abnormality 26/141 (18.4%) 115/141 (81.6%) 0.014 ∗ Pain 11/41 (26.8%) 30/41 (73.2%) 0.40 Storage symptoms 6/30 (20.0%) 24/30 (80.0%) 0.90 Suture used (n; %) 25/131 (19.1%) 106/131 (80.9%) 0.21 Outcomes Complications 5/9 (55.6%) 4/9 (44.4%) 0.02 ∗ Reoperation 3/4 (75.0%) 1/4 (25.0%) 0.02 ∗ ∗ A p-value

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.

Summary 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. Table . Urine culture results for patients with and without bladder debris on renal bladder ultrasound ( p = 0.0048). Bladder debris ( n = 34) No bladder debris ( n = 155) Urine culture Positive 5 (14.7%) E. coli (1) Enterococcus (1) P. mirabilis (2) P. vulgaris (1) 3 (1.9%) E. coli (1) Enterococcus (1) E. cloacae (1) Negative 29 (85.3%) 152 (98.1%)

BACKGROUND: The 2011 American Academy of Pediatrics guidelines state that renal and bladder ultrasound (RBUS) should be performed after initial febrile urinary tract infection (UTI) in a young child, with voiding cystourethrogram (VCUG) performed only if RBUS shows abnormalities. We sought to determine test characteristics and predictive values of RBUS for VCUG findings in this setting. METHODS: We analyzed 3995 clinical encounters from January 1, 2006 to December 31, 2010 during which VCUG and RBUS were performed for history of UTI. Patients who had previous postnatal genitourinary imaging or history of prenatal hydronephrosis were excluded. Sensitivity, specificity, and predictive values of RBUS for VCUG abnormalities were determined. RESULTS: We identified 2259 patients age II in 20.9%, and VUR grade >III in 2.8%. Sensitivity of RBUS for any abnormal findings on VCUG ranged from 5% (specificity: 97%) to 28% (specificity: 77%). Sensitivity for VUR grade >III ranged from 18% (specificity: 97%) to 55% (specificity: 77%). Among the 1203 children aged 2 to 24 months imaged after a first febrile UTI, positive predictive value of RBUS was 37% to 47% for VUR grade >II (13% to 24% for VUR grade >III); negative predictive value was 72% to 74% for VUR grade >II (95% to 96% for VUR grade >III). CONCLUSIONS: RBUS is a poor screening test for genitourinary abnormalities. RBUS and VCUG should be considered complementary as they provide important, but different, information.

Background: Despite availability of validated screening tests for mood disorders, busy general practitioners (GPs) often lack the time to use them routinely. This study aimed to develop a simplified clinical predictive score to help screen for presence of current mood disorder in low-income primary care settings. Methods: In a cross-sectional study, 197 patients seen at 10 primary care centers in Santiago, Chile completed self-administered screening tools for mood disorders: the Patient Health questionnaire (PHQ-9) and the Mood Disorder Questionnaire (MDQ). To determine participants’ current-point mood disorder status, trained clinicians applied a gold-standard diagnostic interview (SCID-I). A simplified clinical predictive model (CM) was developed based on clinical features and selected questions from the screening tools. Using CM, a clinical predictive score (PS) was developed. Full PHQ-9 and GP assessment were compared with PS. Results: Using multivariate logistic regression, clinical and demographic variables predictive of current mood disorder were identified for a simplified 8-point predictive score (PS). PS had better discrimination than GP assessment (auROC-statistic ¼0.80 [95% CI 0.72, 0.85] vs. 0.58 [95% CI 0.52, 0.62] p-value o0.0001), but not as good as the full PHQ-9 (0.89 [95% CI 0.85, 0.93], p-value¼0.03). Compared with GP assessment, PS increased sensitivity by 50% at a fixed specificity of 90%. Administered in a typical primary care clinical population, it correctly predicted almost 80% of cases. Limitations: Further research must verify external validity of the PS. Conclusion: An easily administered clinical predictive score determined, with reasonable accuracy, the current risk of mood disorders in low-income primary care settings.

Objective—To investigate whether differences existed between clinically normal dogs and dogs with goniodysgenesis-related glaucoma (GDRG) in serum autoantibodies against optic nerve antigens. Animals—16 dogs with GDRG, 17 healthy dogs with unremarkable pectinate ligament and iridocorneal angle morphology, and 13 euthanized dogs with no major ocular abnormalities or underlying diseases. Procedures—Western blotting was performed with optic nerve extracts from the euthanized dogs as an antigen source and serum from clinically normal dogs and dogs with GDRG as a primary antibody (autoantibody) source. Blots were evaluated for presence and density of bands. Results—Multiple bands were identified on western blots from all dogs with GDRG and all clinically normal dogs, with a high degree of variability among individual dogs. Dogs with GDRG were significantly more likely than healthy dogs to have bands present at 38, 40, and 68 kDa. Dogs with GDRG had significant increases in autoreactivity at 40 and 53 kDa and a significant decrease in autoreactivity at 48 kDa. Conclusions and Clinical Relevance—Significant differences in serum autoantibodies against optic nerve antigens were found in dogs with versus without GDRG. Although it remains unclear whether these differences were part of the pathogenesis of disease or were sequelae to glaucomatous changes, these findings provide support for the hypothesis that immune-mediated mechanisms play a role in the development or progression of GDRG. However, the high degree of variability among individual dogs and the considerable overlap between groups suggest that the clinical usefulness of this technique for distinguishing dogs with GDRG from clinically normal dogs is likely limited.

To determine the mean and normal range of anteroposterior diameter (APD) of the renal pelves in children.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.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).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 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 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.

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

Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM + ) and basal/myoepithelial (CD10 + ). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM + epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10 + cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10 + breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.

Although the use of nonmyeloablative (NMA) hematopoietic stem cell transplantation (HSCT) regimens has expanded in the past decade, little data exist to support antiviral prophylaxis to prevent herpes zoster (HZ) in recipients who are seropositive for varicella-zoster virus in this population. The present study examined the clinical features, incidence, and risk factors for HZ in a homogeneous cohort of NMA allogeneic HSCT recipients. We conducted a retrospective cohort study assessing all patients who underwent sibling NMA HSCT at Maisonneuve-Rosemont Hospital (Montreal) between July 2000 and December 2008. All patients received the same conditioning regimen, immunoprophylaxis, and graft-versus-host disease therapy. The diagnosis of HZ was defined clinically. Factors associated with HZ were identified using a Cox proportional hazards model. A total of 179 patients were followed for a median of 33 months (interquartile range, 21-59). HZ developed in 66 patients (37%) at a median of 8.3 months post-HSCT; the incidence rate was 175 cases/1000 person-years. The estimated cumulative HZ incidence was 27% at 1 year, 36% at 2 years, and 44% at 3 years. Thoracic dermatomes were most frequently involved (30%); dissemination occurred in 5 patients. No deaths resulted from HZ, but 23% of patients developed postherpetic neuralgia. In multivariate analysis, reactivation of cytomegalovirus and herpes simplex virus was associated with a reduced likelihood of HZ (hazard ratio, 0.54 and 0.33, respectively). Antiviral prophylaxis or treatment for cytomegalovirus and herpes simplex virus reactivations were protective against HZ. The incidence of HZ in our cohort of NMA HSCT recipients is similar to the incidence reported in HSCT recipients who received a myeloablative conditioning regimen. Given the observed high risk, we conclude that recommendations for antiviral prophylaxis should apply, at least for the first year, to the NMA HSCT population as well.

Summary 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 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. Summary Table . Fluoroscopy times and radiation exposure comparing surgeon-control vs. technologist control. Measure Tech Control (N = 36) Surgeon Control (N = 37) Overall (N = 73) P-value Total Fluoro Time (min) 0.2836 Median (IQR) 0.55 (0.65) 0.50 (0.70) 0.50 (0.70) Radiation ESAK (mGy) 0.3616 Median (IQR) 46.99 (72.98) 46.02 (86.18) 46.50 (79.47)

Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S . Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform i mmunoaffinity p roteomics-based t echnology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S . Typhi to capture S . Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S . Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S . Typhi and S . Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S . Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays.

After changing empiric treatment of febrile neutropenia from meropenem to cefepime, the effect on Clostridium difficile infection (CDI) was investigated. The change was assessed using an autoregressive model. A significant increase in CDI rates occurred following the introduction of cefepime. There may be an association between increased cefepime usage and CDI.

Pseudomonas aeruginosa is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis. P. aeruginosa infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported P. aeruginosa PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant ( P < 0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.

Nicotinic agonists may improve attention and memory in humans and may ameliorate some cognitive deficits associated with neuropsychiatric disorders such as schizophrenia.We investigated the effects of a single dose of nicotine on episodic memory performance in 10 adults with schizophrenia and 12 healthy controls. Participants were nonsmokers in order to avoid confounding effects of nicotine withdrawal and reinstatement on memory. At each of two study visits, participants performed a test of episodic memory before and 4 h after application of a 14-mg transdermal nicotine (or identical placebo) patch in counterbalanced order.Compared with placebo, nicotine treatment was associated with more rapid and accurate recognition of novel items. There was a trend for a treatment by diagnosis interaction, such that the effect of nicotine to reduce false alarms was stronger in the schizophrenia than the control group. There was no effect of nicotine on accuracy or reaction time for identification of previously viewed items.These data suggest that nicotine improves novelty detection in non-smokers, an effect that may be more pronounced in non-smokers with schizophrenia. Because memory deficits are associated with functional impairment in schizophrenia and because impaired novelty detection has been linked to the positive symptoms of schizophrenia, study of the effects of chronic nicotinic agonist treatment on novelty detection may be warranted.

Objective There is no approved pharmaco-therapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D(2)/5-HT(2)) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users. Method Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized, double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006. Results Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperi-done reported significantly worsened depressive symptoms (mean +/- SD HAM-D change scores: +7.4 +/- 8.8 vs. -2.3 +/- 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 +/- 9.4 lb vs. -4.0 +/- 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo. Conclusion Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain. Trial registration clinicaltrials.gov Identifier: NCT00385801.

Summary Background Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. Objective This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. Study design A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. Results Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis ( Summary Table ). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. Discussion Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. Conclusions This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD. Summary Table . Group 1 Group 2 Group 3 Group 4 Adjusted P-value Age at diagnosis 2–18 months >18 months unknown n 19 11 7 6 Most recent method of bladder emptying Voiding 7 (36.8%) 3 (27.3%) 2 (28.6%) 1.00 CIC 13 (68.4%)* 8 (72.7%) 5 (71.4%) 1.00 No hydronephrosis on recent ultrasound 13 (68.4%) 5 (45.5%) 3 (42.8%) 0.90 Recent serum creatinine (ng/dl) Median 0.4 0.4 0.55 0.91 IQR 0.3–0.5 0.4–0.7 0.4–0.8 0.91 *One patient utilized both CIC and voiding to empty.

Summary Introduction Augmentation enterocystoplasty and appendicovesicostomy are complex pediatric urologic procedures. Although there is literature identifying long-term outcomes in these patients, the reporting of short-term postoperative outcomes has been limited by small numbers of cases and lack of prospective data collection. Here we report 30-day outcomes from the first nationally based, prospectively assembled cohort of pediatric patients undergoing these procedures. Objective To determine 30-day complication, readmission and reoperation after augmentation enterocystoplasty and appendicovesicostomy in a large national sample of pediatric patients, and to explore the association between preoperative and intraoperative characteristics and occurrence of any 30-day event. Study design We queried the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Pediatric database (ACS-NSQIPP) for all patients undergoing augmentation enterocystoplasty and/or appendicovesicostomy. Surgical risk score was classified on a linear scale using a validated pediatric-specific comorbidity score. Intraoperative characteristics and postoperative 30-day events were reported from prospectively collected data. A composite measure of complication, readmission and/or reoperation was used as primary outcome for the multivariate logistic regression. Results There were 461 patients included in the analysis: 245 had appendicovesicostomy, 97 had augmentation enterocystoplasty and 119 had both procedures. There were a total of 110 NSQIP complications seen in 87 patients. The most common complication was urinary tract infection (see Table for 30-day outcomes by patient). The composite measure of any 30-day event was seen in 27.8% of the cohort and this was associated with longer operative time, increased number of procedures done at time of primary surgical procedure and higher surgical risk score. Discussion The ACS-NSQIPP provides a tool to examine short-term outcomes for these complex urologic procedures that has not been possible before. Although ACS-NSQIP has been used extensively in the adult surgical literature to identify rates of complications, and to determine predictors of readmission and adverse events, its use in pediatric surgery is new. As in the adult literature, the goal is for standardization of practice and transparency in reporting outcomes that may lead to reduction in morbidity and mortality. Conclusion In this cohort, any 30-day event is seen in almost 30% of the patients undergoing these urologic procedures. Operative time, number of concurrent procedures and higher surgical risk score all are associated with higher odds of the composite 30-day event of complication, readmission and/or reoperation. These data can be useful in counseling patients and families about expectations around surgery and in improving outcomes. Table . 30-day events by patient. Patients, n = 461 Any NSQIP complications 87 (18.9) UTI 43 (9.3) Wound complications Superficial SSI 19 (4.1) Deep SSI 4 (0.9) Organ SSI 5 (1.1) Dehiscence 8 (1.7) Pneumonia 1 (0.2) Reintubation 1 (0.2) Bleeding/transfusion 19 (4.1) Sepsis 8 (1.7) Central line infection 1 (0.2) Renal failure 1 (0.2) Other 30-day outcomes Readmission 62 (13.5) Reoperation 32 (6.9) Composite 30-day event 128 (27.8) Data given as n (%).

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.

We describe our experience with 2-stage proximal hypospadias repair. We report outcomes, and patient and procedure characteristics associated with surgical complications.We retrospectively studied patients with proximal hypospadias who underwent staged repair between January 1993 and December 2012. Demographics, preoperative management and operative technique were reviewed. Complications included glans dehiscence, fistula, meatal stenosis, nonmeatal stricture, urethrocele/diverticula and residual chordee. Cox proportional hazards model was used to evaluate the associations between time to surgery for complications and patient and procedure level factors.A total of 134 patients were included. Median patient age was 8.8 months at first stage surgery and 17.1 months at second stage surgery, and median time between surgeries was 8 months. Median followup was 3.8 years. Complications were seen in 71 patients (53%), with the most common being fistula (39 patients, 29.1%). Reoperation was performed in 66 patients (49%). Median time from urethroplasty to surgery for complication was 14.9 months. Use of preoperative testosterone decreased risk of undergoing surgery for complication by 27% (HR 0.73, 95% CI 0.55-0.98, p = 0.04). In addition, patients identified as Hispanic were at increased risk for undergoing surgery for complications (HR 2.40, 95% CI 1.28-4.53, p = 0.01).We review the largest cohort of patients undergoing 2-stage hypospadias repair at a single institution. Complications and reoperation rates were approximately 50% in the setting of complex genital reconstruction.

Summary Background Management of vesicoureteral reflux (VUR) continues to be controversial. In conditions of uncertainty, decision analytic techniques such as cost-utility analysis (CUA) can help to structure the decision-making process. However, CUA analyses require a “utility,” a value between 0 (death) and 1 (perfect health) corresponding to the quality of life associated with a health state. Ideally, utility values are elicited directly from representative community samples, but utilities have not been rigorously measured for pediatric urology conditions. Objectives To elicit utility scores for VUR and open anti-reflux surgery (ARS) from a representative, well-characterized community sample of adults who have been parents. Methods Cross-sectional survey of nationally representative adults who had ever been parents. Each respondent saw one of four descriptions of VUR, with or without continuous antibiotic prophylaxis (CAP) and occurrence of febrile urinary tract infection (UTI). A 6-week postoperative health state following ARS was also assessed. We used the time trade-off (TTO) method to elicit utility scores. Factors associated with utility score were assessed with a multivariate linear regression model. Results The survey was completed by 1200 individuals. Data were weighted to adjust for demographic differences between responders and non-responders. Mean age was 52 ± 15 years, 44% were male, and 68% were White. In terms of education, 29% had a college degree or higher. The mean utility score for VUR overall was 0.82 ± 0.28. VUR utility scores did not differ significantly based on inclusion of CAP or UTI in the health state description (p = 0.21). The 6-week postoperative period garnered a utility of 0.71 ± 0.43. Discussion Our results showed that VUR has a mean utility score of 0.82, which indicates that the community perceives this condition to be a substantial burden. For comparison, conditions with similar utility scores include compensated hepatitis B-related cirrhosis (0.80) and glaucoma (0.82); conditions with higher utilities include neonatal jaundice (0.99) and transient neonatal neurological symptoms (0.95); and conditions with lower utility scores include severe depression (0.43) and major stroke (0.30). Our results suggest that parents consider the burden associated with VUR to be significant, and that the impact of the condition on families and children is substantial. Conclusions VUR is perceived as having a substantial impact on health-related quality of life, with a utility value of 0.82. However, use of CAP and occurrence of UTI do not seem to affect significantly the community perspective on HRQOL associated with living with VUR. Table . Utility scores for VUR, stratified by inclusion of continuous antimicrobial prophylaxis and/or UTI in the VUR health state description (weighted linear regression) Weighted N (%) VUR utility (±SD) Univariate p Overall sample 1200 0.82 ± 0.28 – VUR health state group 0.209 +antibiotic prophylaxis, +UTI 303 (25) 0.84 ± 0.26 +antibiotic prophylaxis, -UTI 292 (24) 0.79 ± 0.30 -antibiotic prophylaxis, +UTI 313 (26) 0.82 ± 0.28 -antibiotic prophylaxis, -UTI 293 (24) 0.81 ± 0.27

The aim of this study was to compare gene expression profiles of leukocytes from blood (white blood cells; WBCs) and spleen harvested at an early time point after injury or sham injury in mice subjected to trauma/hemorrhage, burn injury, or lipopolysaccharide (LPS) infusion at three experimental sites. Groups of injured or LPS-infused animals and sham controls were killed at 2 h after injury and resuscitation, blood and spleen were harvested, and leukocyte populations were recovered after erythrocyte lysis. RNA was extracted from postlysis leukocyte populations. Complementary RNA was synthesized from each RNA sample and hybridized to microarrays. A large number (500–1,400) of genes were differentially expressed at the 2-h time point in injured or LPS-infused vs. sham animals. Thirteen of the differentially expressed genes in blood, and 46 in the spleen, were upregulated or downregulated in common among all three animal models and may represent a common, early transcriptional response to systemic inflammation from a variety of causes. The majority of these genes could be assigned to pathways involved in the immune response and cell death. The up- or downregulation of a cohort of 23 of these genes was validated by RT-PCR. This large-scale microarray analysis shows that, at the 2-h time point, there is marked alteration in leukocyte gene expression in three animal models of injury and inflammation. Although there is some commonality among the models, the majority of the differentially expressed genes appear to be uniquely associated with the type of injury and/or the inflammatory stimulus.

Oral viscous budesonide (OVB) using Splenda as a delivery vehicle has become an attractive therapeutic option for children with eosinophilic esophagitis (EoE). Many families are wary of giving the artificial sweetener in high doses to their children. The aim of the present study was to determine whether OVB mixed with Neocate Nutra, a hypoallergenic nutritional supplement, is at least as efficacious as OVB mixed with Splenda at healing EoE.Our institutional review board approved a retrospective chart review of patients with well-documented EoE treated with OVB at the Boston Children's Hospital Eosinophilic Gastrointestinal Disorder program between June 2008 and June 2013. Primary outcome measured was histologic response defined as change in peak eosinophil count to15 eosinophils per high-power field (eos/HPF) after at least 10 weeks of OVB therapy.A total of 46 children were treated with OVB mixed with Splenda, and 14 were treated with OVB mixed with Neocate Nutra. The 2 groups were not significantly different in their demographic (race, age, sex) or clinical (initial eosinophil count, proton pump inhibitor use, or concomitant dietary elimination) characteristics. On follow-up endoscopy, 30 of 46 patients on Splenda and 13 of 14 patients on Neocate Nutra achieved histologic response. Mean pretreatment and posttreatment peak eosinophil counts for the children taking Neocate Nutra were 62 eos/HPF ([high-power field] range 20-120 eos/HPF) and 9 eos/HPF (range 0-100 eos/HPF), respectively. Mean pretreatment and posttreatment peak eosinophil counts for the Splenda group were 59.5 eos/HPF (range 20-180 eos/HPF) and 25.5 eos/HPF (range 0-200 eos/HPF), respectively. The odds ratio (OR) of success with Neocate Nutra as compared with Splenda was 6.93 (95% CI 0.83-57.91, P = 0.0728), demonstrating the noninferiority of Neocate Nutra.We demonstrate that OVB mixed with Neocate Nutra is at least as effective as OVB mixed with Splenda at treating children with EoE. Neocate Nutra is an innovative, effective, and palatable mixing agent to create a viscous budesonide slurry for families who prefer not to use the standard recipe with Splenda.

Few standards exist for reporting results of voiding cystourethrogram (VCUG). To assess the variation in reporting of VCUG findings from different facilities using a standardized assessment tool. VCUG reports were evaluated for demographic, technical, anatomical and functional information. Reports were categorized by age, gender, indication and vesicouretal reflux (VUR) status. Institutions were classified as a free-standing pediatric hospital (n = 3), pediatric hospital within a hospital (n = 11), or non-pediatric facility (n = 24) and reports were classified as having been read by a pediatric radiologist or not. Each category of outside reports (n = 152) was randomly matched with a twice-larger group of Hospital A reports from the same category (n = 304). Multivariate linear regression was used to analyze the association between the primary outcome (percentage of items described in dictated VCUG report) and the type of radiologist and institution. Of the 456 studies, 66% were in girls, 56% were in those