Gastrointestinal and genitourinary symptoms in facioscapulohumeral muscular dystrophy: Prevalence and impact.

INTRODUCTION/AIMS: Anecdotally, patients with facioscapulohumeral muscular dystrophy (FSHD) describe gastrointestinal (GI) and genitourinary (GU) symptoms. We explored the prevalence of GI and GU symptoms and their impact on quality of life (QOL) in people with FSHD compared to healthy household controls. METHODS: In this descriptive, cross-sectional study, we emailed a survey exploring GI and GU symptoms to all FSHD Society patient contacts (n = 3507). We invited those with FSHD and unaffected household controls to respond. Non-parametric statistics were used to compare symptom frequency and impact of symptoms between respondents with FSHD and household controls. Within the FSHD group, symptom frequency was assessed relative to measures of disease progression (need for ambulatory or respiratory support). RESULTS: Surveys from 701 respondents (652 with FSHD) ≥18 years old were included in analysis. Those with FSHD had symptoms affecting both GI and GU systems more frequently than controls using ordinal rating of symptom frequency. Within the FSHD group, more advanced disease was associated with increased symptom frequency. QOL was negatively impacted by the GI and GU symptoms. There was no difference between groups in use of medications to treat these symptoms. DISCUSSION: Recognition and treatment of GI and GU symptoms in people with FSHD, particularly those with more advanced disease, could improve QOL. Additional investigation is required to confirm these findings and understand the physiology.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans.

BACKGROUND: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations. METHODS: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined. RESULTS: The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1, which is implicated in mucin hypersecretion (p=1.1 ×10-8). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome. CONCLUSION: Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.

Multi-institutional Validation of Improved Vesicoureteral Reflux Assessment With Simple and Machine Learning Approaches.

PURPOSE: Vesicoureteral reflux grading from voiding cystourethrograms is highly subjective with low reliability. We aimed to demonstrate improved reliability for vesicoureteral reflux grading with simple and machine learning approaches using ureteral tortuosity and dilatation on voiding cystourethrograms. MATERIALS AND METHODS: Voiding cystourethrograms were collected from our institution for training and 5 external data sets for validation. Each voiding cystourethrogram was graded by 5-7 raters to determine a consensus vesicoureteral reflux grade label and inter- and intra-rater reliability was assessed. Each voiding cystourethrogram was assessed for 4 features: ureteral tortuosity, proximal, distal, and maximum ureteral dilatation. The labels were then assigned to the combination of the 4 features. A machine learning-based model, qVUR, was trained to predict vesicoureteral reflux grade from these features and model performance was assessed by AUROC (area under the receiver-operator-characteristic). RESULTS: A total of 1,492 kidneys and ureters were collected from voiding cystourethrograms resulting in a total of 8,230 independent gradings. The internal inter-rater reliability for vesicoureteral reflux grading was 0.44 with a median percent agreement of 0.71 and low intra-rater reliability. Higher values for each feature were associated with higher vesicoureteral reflux grade. qVUR performed with an accuracy of 0.62 (AUROC=0.84) with stable performance across all external data sets. The model improved vesicoureteral reflux grade reliability by 3.6-fold compared to traditional grading (P < .001). CONCLUSIONS: In a large pediatric population from multiple institutions, we show that machine learning-based assessment for vesicoureteral reflux improves reliability compared to current grading methods. qVUR is generalizable and robust with similar accuracy to clinicians but the added prognostic value of quantitative measures warrants further study.

Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio.

PURPOSE: The vesicoureteral reflux index is a simple, validated tool for predicting resolution of reflux. Along with likelihood of spontaneous resolution identification of children at risk for febrile urinary tract infection impacts management. We evaluated the usefulness of the vesicoureteral reflux index as a predictive factor for breakthrough febrile urinary tract infection compared to reflux grade and distal ureteral diameter ratio. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram data were identified. A 1 to 6-point index was assigned, and ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 to L3 vertebral bodies. Random forest modeling and logistic multivariable regression were employed to estimate the predictive ability of grade, ureteral diameter ratio and vesicoureteral reflux index with regard to breakthrough febrile urinary tract infection. RESULTS: We analyzed 94 girls and 45 boys with a mean±SD age of 5.4±4.7 months at diagnosis. Mean±SD length of followup was 32.1±24.5 months. A total of 13 children (9.4%) experienced breakthrough febrile urinary tract infection. On univariate analysis ureteral diameter ratio (p=0.01) and vesicoureteral reflux index (p=0.0005) were associated with breakthrough urinary tract infection, while grade (p=0.09) did not reach significance. Area under the curve was generated as a measure of accuracy for each variable and was 0.77 for the vesicoureteral reflux index, 0.71 for ureteral diameter ratio and 0.68 for grade, indicating superiority of the vesicoureteral reflux index for predicting breakthrough febrile urinary tract infection. CONCLUSIONS: Children with higher vesicoureteral reflux index are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. The vesicoureteral reflux index provides valuable prognostic information about infection risk, facilitating improved clinical decision making.

Accuracy of subjective vesicoureteral reflux timing assessment: supporting new voiding cystourethrogram guidelines.

BACKGROUND: Bladder volume at the onset of vesicoureteral reflux (VUR) is an important prognostic indicator of spontaneous resolution and the risk of pyelonephritis. OBJECTIVE: We aim to determine whether pediatric urologists and pediatric radiologists can accurately estimate the timing of reflux by examining voiding cystourethrogram (VCUG) images without prior knowledge of the instilled contrast volume. MATERIALS AND METHODS: Total bladder volume and the volume at the time of reflux were collected from VCUG reports to determine the volume at the onset of VUR. Thirty-nine patients were sorted into three groups: early-/mid-filling reflux, late-filling and voiding only. Thirty-nine images were shown to three pediatric urologists and two pediatric radiologists in a blinded fashion and they were then asked to estimate VUR timing based on the above categories. A weighted kappa statistic was calculated to assess rater agreement with the gold standard volume-based report of VUR timing. RESULTS: The mean patient age at VCUG was 3.1±2.9 months, the median VUR was grade 3, and 20 patients were female. Overall agreement among all five raters was moderate (k=0.43, 95% confidence interval [CI] 0.36-0.50). Individual agreement between rater and gold standard was slight to moderate with kappa values ranging from 0.13 to 0.43. CONCLUSION: Pediatric radiologists and urologists are unable to accurately and reliably characterize VUR timing on fluoroscopic VCUG. These findings support the recently published American Academy of Pediatrics protocol recommending the routine recording of bladder volume at the onset of VUR as a standard component of all VCUGs to assist in a more accurate assessment of the likelihood of resolution and risk of recurrent urinary tract infections.

New trends in voiding cystourethrography and vesicoureteral reflux: Who, when and how?

Vesicoureteral reflux, retrograde flow of urine from the bladder into the upper urinary tract, is one of the most common urological diagnoses in the pediatric population. Diagnosis and subsequent management of urinary reflux have become increasingly debated in the past decade, with divergent opinions over which patients should be evaluated for reflux, and when detected, which children should receive intervention. Although some argue that vesicoureteral reflux is a "phenotype" that often resolves without intervention, others contest that untreated reflux has the potential to cause irreversible renal damage over time. Voiding cystourethrogram images the urethra and bladder during both bladder filling and emptying, as well as the ureters and kidneys when reflux is present, and is considered the gold standard for diagnosing vesicoureteral reflux. Once detected, therapeutic options for urinary reflux are diverse, ranging from observation with or without low-dose antibiotic prophylaxis to a variety of operative interventions. Management should be based on a multitude of factors including patient age, risk of subsequent urinary tract infections, risk of renal parenchymal injury, a given child's projected clinical course and parental preference. Over the past two decades, investigators have elucidated many crucial voiding cystourethrogram findings in addition to grade that provide significant prognostic information and are useful in determining the best course of action for a child on a more individualized basis.

Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary Tract Infection.

PURPOSE: Distal ureteral diameter ratio is an objective measure that is prognostic of spontaneous resolution of vesicoureteral reflux. Along with likelihood of resolution, improved identification of children at risk for recurrent febrile urinary tract infections may impact management decisions. We evaluated the usefulness of ureteral diameter ratio as a predictive factor for breakthrough febrile urinary tract infections. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram were identified. Ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 and L3 vertebral bodies. Demographics, vesicoureteral reflux grade, laterality, presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were tested in univariate and multivariable analyses. Primary outcome was breakthrough febrile urinary tract infections. RESULTS: We analyzed 112 girls and 28 boys with a mean ± SD age of 2.5 ± 2.3 years at diagnosis. Vesicoureteral reflux was grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%) and grade 5 in 10 (7.2%). Mean ± SD followup was 3.2 ± 2.7 years. A total of 40 children (28.6%) experienced breakthrough febrile urinary tract infections. Ureteral diameter ratio was significantly greater in children with (0.36) vs without (0.25) breakthrough febrile infections (p = 0.004). Controlling for vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to 2.26, p <0.0001). CONCLUSIONS: Children with increased distal ureteral diameter ratio are at greater risk for breakthrough febrile urinary tract infections independent of reflux grade. Ureteral diameter ratio provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making.

Vesicoureteral Reflux Index: Predicting Primary Vesicoureteral Reflux Resolution in Children Diagnosed after Age 24 Months.

PURPOSE: The Vesicoureteral Reflux Index is a validated tool that reliably predicts spontaneous resolution of reflux or at least 2 grades of improvement for patients diagnosed before age 24 months. We evaluated the Vesicoureteral Reflux Index in children older than 2 years. MATERIALS AND METHODS: Patients younger than 18 years who were diagnosed with primary vesicoureteral reflux after age 24 months and had undergone 2 or more voiding cystourethrograms were identified. Disease severity was scored using the Vesicoureteral Reflux Index, a 6-point scale based on gender, reflux grade, ureteral abnormalities and reflux timing. Proportional subdistribution hazard models for competing risks identified variables associated with resolution/improvement at different time points. RESULTS: A total of 21 males and 250 females met inclusion criteria. Mean ± SD age was 4.0 ± 2.1 years and patients had a median vesicoureteral reflux grade of 2. The Vesicoureteral Reflux Index score improved by 1 point in 1 patient (100%), 2 points in 25 (67.6%), 3 points in 48 (37%), 4 points in 18 (21.4%) and 5 to 6 points in 4 (18.2%). Female gender (p = 0.005) and vesicoureteral reflux timing (late filling, p = 0.002; early/mid filling, p <0.001) independently predicted nonresolution. Median resolution time based on Vesicoureteral Reflux Index score was 2 months or less in 15.6% of patients (95% CI 11.0-13.8), 3 months in 34.7% (95% CI 25.4-44.1), 4 months in 55.9% (95% CI 40.1 to infinity) and 5 months or more in 30.3% (95% CI 29.5 to infinity). High grade (IV or V) reflux was not associated with resolution at any point. Ureteral abnormalities were associated with lack of resolution in the first 12 to 18 months (HR 0.29, 95% CI 0.29-0.80) but not in later followup. Vesicoureteral Reflux Index scores of 3, 4 and 5 were significantly associated with lack of resolution/improvement compared to scores of 2 or less (p = 0.031). CONCLUSIONS: The Vesicoureteral Reflux Index reliably predicts primary vesicoureteral reflux improvement/resolution in children diagnosed after age 24 months. Spontaneous resolution/improvement is less likely as Vesicoureteral Reflux Index score and time from diagnosis increase.

Vesicoureteral Reflux Index: 2-Institution Analysis and Validation.

PURPOSE: The vesicoureteral reflux index is a novel tool designed to predict spontaneous reflux resolution in infants younger than 2 years. We performed a multi-institutional validation study to confirm the discriminatory power of the vesicoureteral reflux index to predict the vesicoureteral reflux resolution rate in young children. MATERIALS AND METHODS: We identified patients diagnosed with primary vesicoureteral reflux before age 24 months who had 2 or more voiding cystourethrograms available. Demographics, vesicoureteral reflux grade and timing, ureteral anomalies and radiographic outcomes were evaluated. The C-index was estimated for time to event model assessment. RESULTS: A total of 219 girls and 150 boys met study inclusion criteria. Mean ± SD age at diagnosis was 4.7 ± 4.9 months. Of the patients 101 (27.4%) had early to mid filling, 214 (58%) had late filling and 54 (14.6%) had voiding only vesicoureteral reflux. High grade reflux was present in 87 patients (23.6%) and ureteral anomalies were observed in 50 (13.6%). A vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater showed an improvement/resolution rate of 88.2%, 77.3%, 62.3%, 32.1% and 14.3%, respectively. On time to event analysis children with filling phase vesicoureteral reflux (p <0.001), grade 4-5 reflux (p <0.001) and ureteral anomalies (p = 0.003) had significantly longer median time to resolution. Median time to spontaneous resolution was 12.6, 12.7, 15.1, 25.6 and 31 months or greater for a vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater, respectively (C-index 0.305, 95% CI 0.252-0.357). During the study period 65 patients (17.6%) underwent surgical intervention. CONCLUSIONS: The vesicoureteral reflux index is a simple tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in patients diagnosed at younger than 2 years. The index provides valuable prognostic information, facilitating individualized patient care.

Teasing in school locker rooms regarding penile appearance.

PURPOSE: Parents of young boys seeking circumcision or circumcision revision commonly cite concern that their sons may be teased in middle or high school due to the appearance of the penis. There are no current data to substantiate or refute the likelihood of such teasing. We explored the validity of this concern by investigating the extent and frequency of teasing regarding penile appearance. MATERIALS AND METHODS: An anonymous questionnaire was administered to undergraduate men at the University of Iowa. Participants answered questions regarding middle and high school demographics, school sports and gym class participation, and any teasing experienced or witnessed due to penile appearance in locker rooms. RESULTS: A total of 290 men completed the questionnaire. Mean subject age was 19.2 years (range 17 to 24). Of the individuals surveyed 98% were required to participate in high school gym class and 96% participated in a school sport. Of the subjects 10% were teased about their penile appearance and 47% reported witnessing someone else being teased. The most common characteristic singled out was penile size. However, having an uncircumcised penis or a "strange" penile appearance accounted for 33% of the witnessed penile teasing. Only 3% of the cohort wished that they had a different penile appearance. CONCLUSIONS: Teasing in the locker room about penile appearance occurs frequently. While our study is limited to 1 Midwestern university population, it appears that parental concerns regarding teasing related to penile appearance are valid, although most causes of teasing may not be alleviated by surgical therapy.

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PURPOSE: Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. MATERIALS AND METHODS: Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). RESULTS: A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). CONCLUSIONS: Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making.

Controversies in the Management of Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) is the abnormal retrograde flow of urine from the bladder into the upper urinary tract. Diagnosis and subsequent management of VUR have become increasingly controversial, with differing opinions over which children should be evaluated for reflux, and when detected, who should undergo treatment. Management goals include prevention of recurrent febrile urinary tract infection (fUTI) and renal injury while minimizing the morbidity of treatment and follow-up. Management options include observation with or without continuous antibiotic prophylaxis and surgical correction via endoscopic, open or laparoscopic/robotic approaches. Management should be individualized and based on patient age, health, risk of subsequent renal injury, clinical course, renal function, and parental preference.

Tolerance for Ambiguity: Correlations With Medical and Physical Therapy Student Traits and Experiences Within the Learning Environment.

PURPOSE: Health care professions trainees and clinicians who perceive ambiguous situations as sources of threat (low tolerance for ambiguity [TFA]) experience greater risk for mental health disorders and professional burnout. Physical therapists likely encounter substantial ambiguity because of the biopsychosocial nature of their main therapeutic strategies. The purpose of this study was to identify student traits and experiences within the learning environment that differentiate students with high and low TFA for medicine and physical therapy (PT), and to identify areas of interprofessional overlap and distinction. METHOD: Graduation Questionnaire survey data from graduating PT (n = 2,727) and medical students (n = 33,159) from the 2019-2020 and 2020-2021 academic years were sorted according to student TFA score, and respondents in the highest and lowest TFA quartiles were retained for analysis. Difference-in-differences analysis was used to reduce the number of potential explanatory factors to a parimonious subset that was put into linear regression models. Inferential statistics were applied to all significant factors identified from the linear regression models. RESULTS: For both professions, higher TFA was generally associated with more positive ratings of the learning environment (student-faculty interactions, faculty professionalism, satisfaction with career choice), lower experiences of exhaustion and disengagement (the 2 axes of academic burnout), and higher scores for the empathy domain of perspective taking. Uniquely for medical students, low TFA was associated with lower empathy scores and a lower degree of interest in working with underserved individuals. CONCLUSIONS: Findings suggest that for both professions, high TFA corresponded with better ratings of the educational experience and with traits that are advantageous for patient-centered practice and occupational resilience. Interventions to cultivate TFA among health care trainees may be an important way to meet the growing demand for humanistic health care professionals who are prepared to meet society's complex needs.

Ovotesticular cords and ovotesticular follicles: New histologic markers for human ovotesticular syndrome.

INTRODUCTION: The presence of an ovotestis is a rare difference of sex development. The diagnosis can be difficult with the gold standard being the presence of both testicular cords and ovarian follicles within the same gonad. OBJECTIVE: Herein we describe two new markers of ovotesticular syndrome: ovotesticular cords and ovotesticular follicles. STUDY DESIGN: Twenty human gonads with a previous diagnosis of ovotestis were re-stained with markers for testicular cords (SOX9, TSPY, SALL4, DDX4, cP450, AR, α-actin) and ovarian tissue (FOXL2, SALL4, DDX4). Ovotesticular cords were defined as structures expressing both testicular Sertoli cell marker (SOX9) and an ovarian follicular cell marker (FOXL2), and in Y chromosome positive specimens, TSPY-positive testicular germ cells. Ovotesticular follicles were defined as a hybrid ovarian follicle containing FOXL2-positive granulosa cells and a central oocyte, but also containing cells expressing the testicular Sertoli cell marker, SOX9, intermingled within FOXL2-positive granulosa cells and male and female germ cells. RESULTS: Six of twenty ovotestis did not meet our criterion for the diagnosis of ovotestis lacking the histologic evidence of both testicular and ovarian tissue. The remaining 13 patients in which 14 separate specimens were evaluated, contained ovotestis defined by the presence of testicular cords and ovarian follicles. Eleven of the 14 ovotestis specimens (79 %) contained ovotesticular cords. Four of 11 ovotestis specimens (36 %) contained ovotesticular follicles. DISCUSSION: We recommend using eight immunohistochemical markers to diagnose an ovotestis: 1) SOX9, TSPY, SALL4, DDX4, cytochrome P450, AR, smooth muscle α-actin for the testicular component and FOXL2 and SALL4, DDX4 for the ovarian component. SOX9 and TSPY (useful only in the presence of a Y karyotype) are specific testicular markers and FOXL2 the only specific ovarian marker. We found ovotesticular cords and ovotesticular follicles in both human bipolar and mixed ovotestis specimens both with and without the presence of the Y chromosome. The clinical significance of ovotesticular cords and follicles remains unknown. We did not observe any obvious abnormalities in cellular architecture with the juxtaposition of testicular cells and ovarian cells. CONCLUSION: We have identified two new structures in humans with ovotestis, ovotesticular cords and ovotesticular follicles (Figure), which appears to be additional markers to facilitate the diagnosis of ovotesticular gonads.

The impact of the distal ureteral diameter ratio, bladder volume at onset of vesicoureteral reflux, and/or grade in predictive models of clinical outcomes in children with vesicoureteral reflux.

PURPOSE: Vesicoureteral reflux (VUR) grade has been used as a primary factor in assessing a child's risk of clinical outcomes. Unfortunately, grade has poor inter-observer reliability. We hypothesized that more objective and reliable VCUG parameters including the distal ureteral diameter ratio (UDR) and volume at onset of VUR (Vol) may either augment or replace the current grading system to provide more reliable prediction of clinical outcomes. MATERIALS AND METHODS: Multivariate clinical outcome models were analyzed to assess the impact on predictive accuracy by the addition of voiding cystourethrogram (VCUG) data including grade, UDR, and Vol, alone or in combinations. Clinical variables from retrospective review of 841 children's records included age, gender, presentation, VUR laterality, bowel and bladder dysfunction, history of febrile urinary tract infection (UTI), and number of UTIs. The primary outcomes assessed included VUR resolution or persistence and need for operative intervention. RESULTS: Grade, UDR, and Vol were independent predictors of resolution and operative intervention. Vol increased predictive accuracy in resolution models with grade or UDR alone; however, no significant difference occurred in models with the substitution of grade with UDR. CONCLUSIONS: A more reliable classification system for VUR, with improved predictive accuracy regarding clinical outcomes, may be developed incorporating UDR and Vol. Whether VUR grade can be completely replaced by Vol and UDR measurements requires further evaluation with larger number of patients.

Urological manifestations of Duchenne muscular dystrophy.

PURPOSE: Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. MATERIALS AND METHODS: We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. RESULTS: Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. CONCLUSIONS: As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists.

Management of functional constipation in children with lower urinary tract symptoms: report from the Standardization Committee of the International Children's Continence Society.

PURPOSE: We present a consensus view of members of the International Children's Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms. MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary. RESULTS: Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined. CONCLUSIONS: The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings.

Spontaneous vesicoureteral reflux resolution curves based on ureteral diameter ratio.

INTRODUCTION: Various factors influence the clinical course of vesicoureteral reflux (VUR) in the pediatric population. Distal ureteral diameter ratio (UDR) is an objective measure reflective of ureterovesical junction anatomy that has been shown to independently predict both spontaneous resolution and breakthrough febrile urinary tract infection (UTI) in children with primary reflux. UDR resolution curves were created, hypothesizing that a UDR value existed at which spontaneous resolution was unlikely to occur. MATERIALS AND METHODS: UDR was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1-L3 vertebral bodies. Recursive partitioning with 10-fold cross validation methodology for time to event data, utilizing martingale residuals was used to create high and low risk groups based on UDR, and stratified by age at diagnosis and laterality. RESULTS: Three hundred and four patients (226 female, 78 male) were analyzed with a mean age at diagnosis of 1.55 ± 1.98 years. Unilateral reflux (p = 0.02), VUR grades 1-3 (p < 0.001), and lower UDR (p < 0.001) were associated with spontaneous resolution on univariate analysis. UDR values were categorized into risk groups based on recursive partitioning. Low risk patients (those with UDR <0.30) achieved VUR resolution faster and with a continuing rate compared to the high-risk group (≥0.30), which had persistent reflux after 3 years [Summary Figure]. When the 0.30 cutoff was applied randomly to patients in test group, the cutoff significantly discriminated between low and high-risk patients (log rank test p = 0.02). DISCUSSION: Primary VUR is often a self-limiting diagnosis, with conservative management favored in low-risk children, UDR may be used to help distinguish those children who may benefit from intervention. Unlike traditional VUR grading where children with any grade of reflux may spontaneously resolve, there appears to be a consistent UDR cutoff whereby patients are very unlikely to spontaneously resolve, regardless of length of follow-up. Therefore, parents of children with a UDR above the 0.3 cutoff, regardless of VUR grade, may be counselled that VUR is very unlikely to resolve over time - thereby reducing the number of VCUGs and length of time these patients are on prophylactic antibiotic prior to surgical intervention. CONCLUSIONS: Children with primary VUR and a UDR of greater than 0.30 are significantly less likely to spontaneously resolve regardless of length of follow-up, and resolution after 3 years was rare. UDR provides objective prognostic information facilitating individualized patient management.

What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee.

INTRODUCTION: The degree of chordee associated with hypospadias impacts operative management. Unfortunately, poor inter-observer reliability in assessing chordee by multiple methods in vitro has been demonstrated. This variability may be related to the fact that chordee is not a discrete angle, but rather an arc-like curvature similar to that of a banana. On an attempt to improve this variability, we assessed the inter-rater reliability of a novel method of chordee measurement and compared it to measurements with a goniometer both in vitro and in vivo. MATERIALS AND METHODS: In vitro assessment of curvature was performed using 5 bananas. In vivo chordee measurement was performed during 43 hypospadias repairs. On in vitro and in vivo cases, chordee was assessed independently by faculty and resident physicians. Angle assessment was performed in a standard manner with a goniometer and with a smartphone app using ruler measurements of the length and width of the arc (Summary Figure). The proximal and distal aspect of the arc to be measured was marked on the bananas, whereas the penile measurements were taken from the penoscrotal to the sub-coronal junctions. RESULTS: In vitro banana assessment demonstrated strong intra- and inter-rater reliability for length (0.89 and 0.88, respectively) and width measurements (0.97 and 0.96). The calculated angle demonstrated an intra- and inter-rater reliability of 0.67 and 0.67. The banana goniometer/protractor measurements were weak with an intra-rater and inter-rater reliability of 0.33 and 0.21. With hypospadias chordee, the inter-rater reliability was strong for length and width measurements (0.95 and 0.94) and 0.48 for calculated angle. The inter-rater reliability of the goniometer angle was 0.96. Further assessment of inter-rater goniometer reliability was performed relative to degree of chordee as characterized by faculty. The inter-rater reliability for ≤15°, 16-30, and ≥30° was 0.68 (n = 20), 0.34 (n = 14), and 0.90 (n = 9), respectively. When the goniometer angle was classified as ≤15, 16-30, or ≥30° by one physician, it was classified outside of this range by the other physician 23%, 47%, and 25% of the time, respectively. DISCUSSION: Our data demonstrate significant limitations of the goniometer for assessing chordee in vitro and in vivo. We were unable to demonstrate significant improvement in chordee assessment using arc length and width measurements to calculate radians. CONCLUSIONS: Reliable and precise techniques for measuring hypospadias chordee remain elusive and draw into question the validity and usability of management algorithms employing discrete values.

Decisional conflict in American parents regarding newborn circumcision.

BACKGROUND: Decisional conflict surrounding the topic of circumcision in the newborn male is assumed in some parents but has not been quantified or qualified. It is known that parents often base their decision on cultural and social factors and that physician discussions do affect ultimate decision-making. Information on parents' decision-making surrounding newborn circumcision and ways to mitigate conflict or uncertainty around the decision-making process is needed to better counsel them appropriately. OBJECTIVES: To identify the presence or absence of decisional conflict in parents-to-be deciding whether or not to circumcise their child as well as to identify determinants of this conflict to direct future educational measures. STUDY DESIGN: Parents presenting to obstetrics clinic as well as contacted by institutional email were recruited using convenience sampling and completed the validated Decisional Conflict Scale (DCS). A smaller subset of subjects were recruited via institutional email to complete semi-structured interviews regarding the decision-making process and specifically uncertainty regarding the decision. Descriptive statistics and unpaired t tests were used for analysis of survey data. For interview data, an iterative, grounded theory methodology was used. RESULTS: 173 subjects completed the DCS. 12% of all participants had high decisional conflict. Intuitively, those who had not yet decided whether to circumcise had the highest proportion of high DCS (69%), followed by those who had decided to circumcise (9.3%) and those who had decided not to circumcise (1.7%). 24 subjects were interviewed, and based on their DCS scores and interview responses were classified as low, intermediate and high conflict. Three primary themes emerged delineating the high from low conflict groups. There were notable differences in the feelings of subjects regarding knowledge and feeling informed, the importance of particular values and clarity of the roles of these values in decision-making, and feelings of supported decision-making. These themes were used to create a visual model depicting the individual needs of each decision-maker (Fig. 1). DISCUSSION: This study highlights the need for decision support for parents that is not only information-based but focuses on values clarity and supported decision-making. This study provides a jumping-off point for creation of shared decision-making tools directed at individual needs. The limitations of this study are a single institution design and homogeneous population, so when designing materials, additional unrecognized needs will likely be identified. CONCLUSION: A small, but real proportion of parents-to-be experience significant uncertainty around the decision to circumcise their newborn boys. Identified needs of parents include feeling informed, feeling supported and clarification of important values related to the problem.