Summary Figure Research Articles

Provider perspectives on shared decision-making regarding hypospadias surgery

Many parents experience decisional conflict and decisional regret around hypospadias surgery. The utilization of a shared decision-making (SDM) process may mitigate these issues, however addressing the principal components of the SDM process is a complex task that requires the investment of providers. The purpose of this study was to facilitate a discussion about SDM anchored on hypospadias with pediatric urology and general pediatric providers to explore perspectives, clinical applications and barriers to adopting SDM in clinical practice. We conducted two focus groups in order to engage pediatric urology and general pediatric providers in guided discussions about SDM anchored on hypospadias. All activities were audio recorded and professionally transcribed. The transcripts were analyzed by three coders using directed qualitative content analysis techniques to identify themes and relationships between themes to inform the development of an affinity diagram (Extended Summary Figure). Two focus groups were held; one with seven pediatric urology providers in November 2018 and one with ten general pediatric providers in January 2019 (median age 51 years, 88.2% Caucasian, 58.8% female, 70.6% physicians and 29.4% nurse practitioners). Both groups identified some of the key components of SDM including engaging families in decision-making, informing them about treatment options and clarifying values/preferences (Extended Summary Figure). They thought that SDM was useful for discussing preference-sensitive conditions (e.g. hypospadias) and addressing parental compliance. General pediatric providers also suggested that SDM helped them avoid unnecessary referrals to specialists. Both groups identified parental, provider and systemic barriers to the adoption of SDM: a) desire for paternalism, b) misperceptions about medical evidence, c) completion of parental decision-making prior to the clinical visit, d) provider bias/lack of interest and e) time constraints/productivity pressures. Providers who care for hypospadias patients are knowledgeable about SDM and its potential clinical applications. They identified several potentially modifiable barriers to the adoption of a SDM process about hypospadias surgery in a pediatric clinical setting. Based on feedback from providers, we plan to implement a hypospadias decision aid early in the parental decision-making process about hypospadias such as in the postpartum unit and at well-child visits in the newborn period and provide a provider training session about SDM to address the identified knowledge gaps.

The long-term added value of voiding school for children with refractory non-neurogenic overactive bladder: an inpatient bladder rehabilitation program

Despite adequate management, 20% of children with overactive bladder(OAB) syndrome fail to improve their bladder function. To approach the need for alternative strategies, an inpatient bladder rehabilitation 'voiding school' program was established. The objective of this study was to evaluate the short- and long-term (1-year follow-up) outcome of this voiding school program in children with refractory OAB. In addition, the authors aimed to identify which children achieved the best outcomes with this voiding school program. The charts of all children (n=357, mean age: 9.7±2.0 years, 63.6% boys) with refractory OAB who attended voiding school between 2000 and 2010 were reviewed. A linear mixed model with random intercept was used to evaluate the incontinence (expressed by enuresis and daytime incontinence voiding scores) and maximal voiding volume (MVV). This study demonstrated an overall beneficial long-term effect of the inpatient program on day- and night-time incontinence, in which 36.6% of children achieved dryness during day- and night-time. In addition, the mean overall decline in the number of wet nights and days declined with 4 extra dry days and/or nights per week, in comparison with the level of continence before attending the voiding school program. In contrast, only a temporary increase in MVV was seen, however, without relapse incontinence. At last, the authors identified the negative impact of decreasing age, male sex, dysfunctional voiding and nocturnal polyuria on the overall outcome of the inpatient program. An inpatient rehabilitation 'voiding school' program is a successful and safe treatment modality for children with refractory OAB that results in long-term significant increase of continence, as well as amelioration in degree of severity. The worst outcomes of this voiding school program were detected in children with young age, who were boys, or had associated nocturnal polyuria, dysfunctional voiding, and/or faecal incontinence.

Changes in differential renal function after pyeloplasty in infants and children

Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in pediatric populations. Many need surgical intervention. The aim of surgery is preserving renal function and reducing symptoms such as urinary tract infections and pain. The objectives were to evaluate differential renal function (DRF) in infants and children after surgery for UPJO and to identify factors predicting postoperative improvement. The difference in outcomes between patients with antenatal hydronephrosis and those diagnosed later was evaluated. A total of 85 children (63 boys and 22 girls) aged 0-16 years, treated for UPJO with dismembered pyeloplasty, were followed up as per a structured protocol including ultrasounds and renal scans (MAG-3) pre-operatively and three and 18 months postoperatively. Five children with bilateral or single kidney UPJO were excluded. Patient records were retrospectively reviewed, and the patients were grouped as per prenatal (group 1, n=23) or postnatal (group 2, n=57) diagnosis. Univariable and multivariable logistic regression analyses searching for factors predicting >5% postoperative improvement in DRF on the obstructed side were performed. Factors included in analyses were age at diagnosis and surgery, sex, type of presentation, cause of obstruction, estimated glomerular filtration rate, pre-operative DRF, anteroposterior diameter (APD), APD/renal parenchymal thickness, and grade of hydronephrosis as per the Onen alternative grading system (grade 1-4). Pre-operative DRF on the obstructed side was a mean of 42% (standard deviation, 12), with no difference between the groups. The median age at surgery was 0.9 (0.2-10) and 8.1 (0.6-16) years in groups 1 and 2, respectively (P<0.001). The majority had unchanged DRF 18 months postoperatively, 19 (27%) patients improved by >5%, and one deteriorated. The proportion of patients with improved DRF was higher in group 1 (n=10; 45%, P=0.026). Anteroposterior diameter, APD/parenchymal thickness, pre-operative DRF, and antenatal diagnosis were predictors in the univariable analyses, and high APD (odds ratio [OR] = 1.1, P=0.0023), antenatal diagnosis (OR = 0.23, P=0.048), and low pre-operative DRF (OR = 0.90, P=0.0045) built the best model of independent factors predicting improvement in DRF in multivariable analyses (Summary Figure). The limitation of the study is that it is retrospective, but it has the advantage of auniform follow-up protocol, including patients from a five-year period, with few lost to follow-up. The results can be of interest in evaluating factors of importance for predicting recovery of function in obstructive uropathies in children. The majority of children had preserved or improved function after surgery for UPJO. Those with an antenatal diagnosis displayed a greater ability to catch up in DRF, and high APD, antenatal diagnosis, and low pre-operative DRF were independent predictive factors of an improvement in renal function after pyeloplasty.

Evaluation of health-related quality of life and affecting factors in child with enuresis

Enuresis is a common problem in children and distressing condition that can have an impact on the child's behavior and on their emotional and social life. Health-related quality of life (HRQoL) is defined as an individual's perception of the impact of the disease and treatment. The aim of this study was to evaluate the HRQoL in Turkish children with enuresis and to investigate the effect of independent sociodemographic and clinical variables on HRQoL in children with enuresis. 110 children with enuresis and their mothers and 120 healthy children and their mothers were included in the study. The German quality of life questionnaire (KINDL®) scales were used to assess the children's HRQoL. For comparing the data of children with enuresis and healthy children, a two-sided unpaired t-test and linear regression model were used. The total HRQoL score for the children with enuresis group was 63.14±21.98 and for the children in the control group was 75.6±10.1 (P<0.001). After adjusting for sex and age using the unstandardized coefficient of regression model, HRQoL score for the children with enuresis still remained statistically significant lower than that for healthy peers (64.21± vs 75.11± P<0.001). The HRQoL subscale scores showed that children with enuresis had lower emotional well-being scores (64.23±14.2 vs 78.9±11.4, P<0.001), self-esteem score (62.23±11 vs 68.6±17.4, P=0.001), family relationship score (76.23±2 vs 83.4±12.2, P=0.042), and friendship score (62.4±13.2 vs 68.8±15.3, P=0.023) compared to the control group. When the effects of independent sociodemographic factors and clinical variables on HRQoL were evaluated, it was seen that the presence of lower urinary tract symptoms (LUTS) negatively affected total HRQoL score (59.89±11.2 vs 69.29±10.9 P=0.028). Also the total HRQoL score was higher in treated children with enuresis than in nontreated children (65.96±12.1 vs 55.27±10.1 P=0.032). Among the treated children, complete treatment response group had higher total HRQoL score compared to partial treatment response group and nonresponse group (respectively, 70.98±9.7, 65.25±10.1, 60.45±10.9, P=0.034, P=0.01) (Summary Figure). Family income level affected total HRQoL score, low-income group had lower total HRQoL score compared to high-income group (62.17±11.9 vs 69.25±10 P=0.039). This study demonstrated that enuresis negatively affects the HRQoL of children and most affected domains in HRQoL were self-esteem, emotional well-being, and their relationship for family and friends. Our presented study showed that HRQoL was lower in non-primary monosymptomatic nocturnal enuresis (non-PMNE) children, nontreated patients. Also there were higher HRQoL scores in patients who had a total or partial response to treatment. Our study may indicate that, low-income children with enuresis, nontreated enuretic children, and presence of LUTS should be considered as a risk group for low HRQoL.

Consulting “Dr. YouTube”: an objective evaluation of hypospadias videos on a popular video-sharing website

Parents who make decisions about hypospadias repair for their child may seek information from online platforms such as YouTube. The purpose of this study is to evaluate the health literacy demand of hypospadias videos on YouTube using the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V). We performed a YouTube search using the term "hypospadias," limiting results to the first 100 videos. We excluded videos that were <1min or >20min and videos that were not in English or did not include subtitles. Two evaluators independently examined videos and determined PEMAT-A/V scores for understandability and actionability (i.e., ability to identify actions the viewer can take). Videos with scores >70% are understandable or actionable. The inter-rater reliability (kappa) and intraclass correlation coefficient (ICC) of PEMAT scores were calculated. Bivariate and multivariable linear regression models assessed the association of video characteristics with respective scores. Of the 100 videos that were identified on YouTube, 47 (47%) were excluded leaving 53 for analysis: 14 were >20min, 14 were <1min, 9 had no audio or subtitles, 7 were not in English, 1 was a duplicate, 1 was unrelated to hypospadias, and 1 was deleted at the time of data analysis. Three (5.6%) were understandable (mean score 54.5%, standard deviation (SD) 14.9) and eight (15.1%) were actionable (mean score 21.8%, SD 16.6) (Extended Summary Figure). Kappa values ranged from 0.4 to 1. The ICC's were 0.55 and 0.33 for understandability and actionability, respectively. In the bivariate analysis, mean understandability scores were significantly higher for English language videos (p=0.04), videos with animation (p=0.002), and those produced by industry (p=0.02). In the multivariable analysis, mean understandability scores were significantly higher for "expert testimonial" or "other" video types after adjusting for graphics type and overall tone (p=0.04). Mean understandability scores were also significantly higher for videos with animation after adjusting for video type and overall tone (p=0.01). Mean actionability scores were significantly higher for videos with a negative tone (p=0.01). The vast majority of hypospadias-related YouTube content is not appropriate for users with low health literacy although certain types of videos, such those with animation and expert testimonials, scored higher on understandability than other types. Due to the lack of sufficient online informational content regarding hypospadias, we plan to engage parents of sons with hypospadias in the development of high-quality patient educational materials about hypospadias.

Non-palpable testis: is management consistent and objective?

Diagnostic laparoscopy is recommended for boys with non-palpable testis (NPT) by American and European guidelines with the decision to pursue inguinal exploration based upon testicular vessel appearance. We hypothesized that management decisions are not consistent with the guidelines, and that assessment of vessels is subjective. Pediatric urologist management decisions were evaluated via an electronic survey to determine impact of contralateral testicle size, sonographic findings, surgeon region, and years in practice. In a digital image survey, surgeons were asked to interpret gonadal vessel status of 32 consecutive cases of NPT with absent abdominal testis as normal, atretic, or blind-ending to determine intra- and inter-rater reliability. Of the 339 participants, more Europeans (49%) chose sonography as the first management step for NPT compared to US surgeons (12%). Regardless of sonographic findings, over 80% chose laparoscopy as the first step. In the presence of normal, atretic, and blind-ending vessels, the decisions to proceed with inguinal/scrotal exploration were 88%, 68%, and 17%, respectively. Contralateral hypertrophy and sonography findings had no significant impact on the decision to proceed with inguinal/scrotal exploration. The visual gonadal vessel survey showed surgeon interpretation of normal or blind-ending vessels had moderate inter-rater reliability. Surgeons did not agree on normal status 37% of the time and did not agree on atretic status 66% of the time. There was no statistical difference between European and US respondents (P=0.23). Intra-rater reliability was fair for blind-ending vessels. When the first interpretation was blind-ending, the same surgeon changed interpretation of the same image 39% of the time. There was no statistical difference by years of practice. Non-visualization of NPT on sonography and contralateral testis size had no significant impact upon management decisions. Surgeons chose to pursue inguinal/scrotal exploration based upon laparoscopic gonadal vessel status. However, these interpretations were subjective with low inter- and intra-rater reliability.

Sexual function and voiding status following one stage feminizing genitoplasty

The data on long-term outcome of feminizing genitoplasty (FG) with regardto the sexual function and voiding status is limited and nearly always retrospective, reviewing only small numbers of patients. Furthermore, most articles only looked at the success as an adequately open vagina with a feminized appearance. Success should include normal erotic sensation, lubrication, sexual satisfaction, orgasm, and intercourse without discomfort. These latter factors are just beginning to be studied OBJECTIVE: To investigate sexual function and voiding status in women who underwent vaginal reconstruction in childhood. We retrospectively reviewed medical files of patients who underwent FG at our center from 1988 to 2000. In addition, patients were asked to complete the following standardized questionnaires: Female Genital Self-Image Scale (FGSIS), dysfunctional voiding and incontinence symptoms score (DVISS), and Female Sexual Function Questionnaire (FSFI). patients underwent one-stage FG; of those, 36 with median age of 21 years (range 18-30 years) who completed the puberty period were included into this study. Of the participants, 15 (41.6%) lived in a committed partnership, and 12 (80%) had sexual intercourse on a regular basis. Total FSFI was 22.2+3.1 (mean+ SE). Domain scores were 3.9, 4.3, 4.5, 4.3, 4.9, and 4.7 for desire, arousal, lubrication, orgasm, satisfaction, and pain, respectively (Summary Figure). None of the patients reported on daytime incontinence or enuresis. Female genital self-image was found to be positive in all patients and related positively to women's sexual function. The general rate of the sexual activity of our studied population was similar to that published in the literature 80% in our study vs 60-87% published in the literature. The overall FSFI was 22, showing some evidence of the female sexual dysfunction. However, only one patient regarding pain during vaginal penetration demonstrated mild dyspareunia. At the same time, we have not found any desire, arousal, lubrication, orgasm, satisfaction problems. Furthermore none of our patients complained on lower urinary tract symptoms during questioning, while three girls with congenital adrenal hyperplasia presented during follow-up with dribbling incontinence, which resolved with introitoplasty and creation of the wide vaginal opening. Our data demonstrate that one -tage FG in childhood is a long-term effective surgical procedure that does not cause voiding dysfunction. If a secondary intervention is required prior to the sexual life, simple introitoplasty usually solves the problem. The FSFI score showed overall acceptable sexual function, whereas mild dyspareunia was a major complain.

NEW IMMUNIZATION SCHEDULE EFFECTIVENESS AGAINST HEPATITIS B IN LIVER TRANSPLANTATION PATIENTS.

Although liver transplantation is considered to be a high-risk procedure, it is well-established as a treatment option for the cure and quality of life enhancement for individuals who suffer from diseases. Preventing an infection by hepatitis B virus through immunization schedules has been the most effective way to reduce complications, since it decreases the number of people who suffer from chronic hepatitis caused by the hepatitis B virus and eradicates its transmission. 1. Analyzing evidence in the literature on various schedules employed for immunization against hepatitis B in patients who have received a liver transplantation. 2. Suggesting potential immunization schedules against hepatitis B in patients who suffer from liver cirrhosis, without previous verifying documentation, using the Child-Turcotte Pugh score, according to evidences found in the literature. Systematic review of the literature, conducted on the data bases MedLine, PubMed, and Lilacs, between September, 2017 and January, 2018, by using the following keywords: "Liver Transplantation, "Immunization Schedule", "Hepatitis B Vaccines". In order to analyze the articles, a summary figure was especially designed and both the results and discussion were presented in a descriptive way. We included 24 studies; among them, eight had accelerated immunization schedules, 13 followed the conventional schedules, and three had super accelerated schedules. Regarding immunization, 21 studies were conducted with patients in the pre-transplant period, one with a transplanted patient, one with a pre-transplant group, and one with a post-transplant group. Found articles suggest that, disregarding the chosen immunization schedule, seroconversion rates tended to be lower as the liver disease advanced, compared to the healthy population. The studies did not find seroconversion superiority between the different immunization schedules (conventional and unconventional). However, since candidates to liver transplantation are usually very vulnerable, results show that super accelerated immunization schedules are possibly recommended for such group of patients; serologic test results will be higher when the immunization schedule is completed in the pre-transplant period.

Assessment and validation of a screening questionnaire for the diagnosis of pediatric bladder and bowel dysfunction

Pediatric bladder and bowel dysfunction (BBD) is a common problem in children. However, the current ability to diagnosis and quantify pediatric BBD is limitedas only a few validated instruments exist. In addition, the current questionnaires are limited by their lack of psychometric processing and methods of validation. To address these issues, the authors developed a new questionnaire to objectively diagnose pediatric BBD symptoms. This study aimed to evaluate the performance of this newly devised objective instrument in diagnosing and quantifying the symptomatology of BBD in children. An 18-item, 5-point questionnaire was developed using both a literature review and expert opinions. The total questionnaire score could range from 0 to 72. Questions were subgrouped into six symptom categories: (1) nocturnal enuresis, (2) lower urinary tract symptoms, (3) urinary holding, (4) infrequent urination, (5) bowel symptoms, and (6) daytime urinary incontinence. The questionnaire also assessed the degree of bother associated with the symptoms. Patients were divided into cases and controls, and these two groups were compared. A total of 1265 new patients (758 cases and 507 controls) completed the new BBD questionnaire. The mean age of the whole study cohort was 9.5 years (range, 3-19 years). The total mean questionnaire score was significantly higher at 23 (3-58) in the cases, compared with 8 (0-35) in the controls (p<0.001) (Summary Figure). Reliability analysis of the 18-item instrument showed a Cronbach's alpha reliability coefficient of 0.80 for the scale. This new instrument provides a valid and reliable method for diagnosis of pediatric BBD and classification of patients into subcategories of BBD based on their specific symptoms.

Use of small intestinal submucosa for corporal body grafting in cases of epispadias and epispadias/exstrophy complex

Male epispadias is a rare congenital urogenital anomaly in which the meatus is ectopically located along the dorsal midline of the penile shaft. In cases associated with severe curvature, functional and cosmetic outcomes could be accomplished by lengthening the shorter dorsal surface with the use of corporal grafting. Various graft materials have been used in the past for hypospadias repair including tunica vaginalis, dermis, and small intestinal submucosa (SIS). The use of SIS grafting for corporoplasty during epispadias repair has rarely been described in the literature. To report the experience in the management of dorsal corporal body grafting using SIS in children with severe penile curvature due to epispadias. The authors retrospectively reviewed the charts of all patients with epispadias or bladder exstrophy/epispadias complex and severe dorsal chordee (>40°) who underwent epispadias repair with single-layer SIS for corporal body grafting. Clinical variables, surgical technique, and outcomes were analyzed. A total of nine consecutive patients underwent staged epispadias repair with dorsal corporal single-layer SIS grafting (summary figure). Of these, four (44.4%) had primary penopubic epispadias, one (11.1%) had mid-shaft epispadias, and four (44.4%) had bladder exstrophy/epispadias complex. The mean age at surgery was 13.4±6 months. After phalloplasty with SIS grafting, there were no reported complications related to the graft during the post-operative period or follow-up visits. Although traditional techniques for epispadias repair allow some degree of corporal lengthening, they also result in abrupt medial rotation of the corporal bodies leading to torqueing and potential unsatisfactory cosmetic results. In contrast, the authors use single-layer SIS for corporal body grafting, and this study technique results in a more gradual inward rotation thus allowing more anatomical accuracy. Furthermore, an advantage of the use of SIS over other grafting materials is that there is no need to harvest an autologous graft such as tunica vaginalis or dermis. Epispadias repair using single-layer SIS corporal body grafting is an effective, safe, and feasible method, which provides satisfactory cosmesis and correction of dorsal curvature in congenital epispadias in children. Furthermore, a more normal penis appearance, without a decrease in the corporal length or diameter, is achieved with this technique.

The association of postnatal urinary tract dilation risk score with clinical outcomes

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.

Parental perspectives on decision-making about hypospadias surgery

Many parents who choose hypospadias repair for their son experience decisional conflict and regret. The utilization of a shared decision-making process may address the issue of decisional conflict and regret in hypospadias repair by engaging both parents and physicians in decision-making. The objective of this study was to develop a theoretical framework of the parental decision-making process about hypospadias surgery to inform the development of a decision aid. We conducted semistructured interviews were conducted with parents of children with hypospadias to explore their role as proxy decision-makers, inquiring about their emotions/concerns, informational needs, and external/internal influences. Interviews were conducted until no new themes were identified, analyzing them iteratively using open, axial, and selective coding. The iterative approach entails a cyclical process of conducting interviews and analyzing transcripts while the data collection process is ongoing. This allows the researcher to make adjustments to the interview guide as necessary based on preliminary data analysis in order to explore themes that emerge from early interviews with parents. Grounded theory methods were used to develop an explanation of the surgical decision-making process. Sixteen mothers and one father of seven preoperative and nine postoperative patients (n=16) with distal (8) and proximal (8) meatal locations were interviewed. Four stages of the surgical decision-making process were identified: (1) processing the diagnosis, (2) synthesizing information, (3) processing emotions and concerns, and (4) finalizing the decision (Extended Summary Figure). Core concepts in each stage of the decision-making process were identified. Primary concerns included anxiety/fear about the child not waking up from anesthesia and their inability to be present in the operating room. Parents incorporated information from the Internet, medical providers, and their social network as they sought to relieve confusion and anxiety while building trust/confidence in their child's surgeon. The findings of this study contribute to our understanding of decision-making about hypospadias surgery as a complex and multifaceted process. The overall small sample size is typical and expected for qualitative research studies. The primary limitation of the study, however, is the underrepresentation of fathers, minorities, and same-sex couples. This study provides an initial framework of the parental decision-making process for hypospadias surgery that will inform the development of a decision aid. Future stages of decision aid development will focus on recruitment of fathers, minorities, and same-sex couples in order to enrich the perspectives of our work.

A novel approach for an old debate in management of ureterocele: long-term outcomes of double-puncture technique

To date, the optimal surgical technique for ureterocele complex remains unclear and a diverse range of management options have been suggested. Some endoscopic approaches share major drawbacks such as de novo vesicoureteral reflux (VUR) into ureterocele moiety that can mandate revision surgery. In this study, long-term outcomes of double-puncture technique are evaluated. Records of patients treated by double-puncture technique between 1999 and 2014 were reviewed. Patients with a history of previous ureterocele surgery, follow-up period of less than two years, or an orthotopic ureterocele were excluded. In this technique, a double-J stent is inserted into two punctured sites at the poles of an ectopic ureterocele. Subsequently, anterior and posterior collapsed walls of a ureterocele were fulgurated at multiple points to create surface welding of the urine channel. Follow-up data regarding success of ureterocele decompression, de novo VUR, febrile urinary tract infection (UTI), and the need for further intervention were recorded. Forty-eight patients (51 ureteroceles) were assessed in this study. Bilateral ureterocele double puncture was performed for three patients (6.3%). Mean (range) age at the time of surgery was 2.9 (2 months-13 years) years. Mean follow-up was 6.1 (2-15.2) years. Successful decompression was achieved in all except two ureteroceles (success rate=96.1%) (Summary Figure). New-onset VUR to punctured moiety was diagnosed in another two patients. No postoperative febrile UTI was encountered. Double-puncture technique is a successful endoscopic intervention for immediate and durable decompression of ectopic ureteroceles without incurring major complications.

Bidirectional Degradation of DNA Cleavage Products Catalyzed by CRISPR/Cas9

Since the initial characterization of Streptococcus pyogenes CRISPR/Cas9 as a powerful gene-editing tool, it has been widely accepted that Cas9 generates blunt-ended DNA products by concerted cleavage of the target (tDNA) and non-target (ntDNA) strands three nucleotides away from the protospacer adjacent motif (PAM) by HNH and RuvC nuclease active sites, respectively. Following initial DNA cleavage, RuvC catalyzes 3′→5′ degradation of the ntDNA resulting in DNA products of various lengths. Here, we found that Cas9 selects multiple sites for initial ntDNA cleavage and preferentially generates staggered-ended DNA products containing single-nucleotide 5′-overhangs. We also quantitatively evaluated 3′→5′ post-cleavage trimming (PCT) activity of RuvC to find that ntDNA degradation continues up to the −10 position on the PAM distal DNA product and is kinetically significant when compared to extremely slow DNA product release. We also discovered a previously unidentified 5′→3′ PCT activity of RuvC which can shorten the PAM proximal ntDNA product by precisely one nucleotide with a comparable rate as the 3′→5′ PCT activity. Taken together, our results demonstrate that RuvC-catalyzed post-cleavage trimming ultimately generates DNA fragments with heterogeneous ends following initial DNA cleavage including a PAM proximal fragment with a blunt end and a PAM distal fragment with a staggered-end, 3′-recessed on the ntDNA strand. These kinetic and biochemical findings underline the importance of temporal control of Cas9 during gene-editing experiments and help explain the patterns of nucleotide insertions at sites of Cas9-catalyzed gene modification in vivo. Support or Funding Information Florida State University startup fund and a Pelotonia Idea Research Program Award from The Ohio State University Comprehensive Cancer Center A summary figure of my abstract This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prenatal extravasation of urine seems to preserve renal function in boys with posterior urethral valves

A posterior urethral valve(PUV) may lead to extravasation of urine, resulting in prenatal ascites and/or perirenal urinoma. Extravasation has been presumed to act as a pop-off mechanism, preserving renal function, but previous reports addressing this presumption have been inconclusive. The present study compares renal function in patients with PUV with and without extravasation. Sixty boys with a confirmed diagnosis of PUV as neonates (gestational age [GA]<44 weeks) throughout 2001-2016 were included. Clinical data were collected from medical records. Renal function was assessed by nadir plasma creatinine, creatinine at the last follow-up, and glomerular filtration rate (GFR) at the last follow-up. The GFR was estimated using the Schwartz formula. Renal function was classified according to the kidney disease: improving global outcomes (KDIGO) guidelines' grades of chronic kidney disease (CKD). Glomerular filtration rate > 90ml/min/1.73m2 at the last follow-up was classified as normal renal function. Twelve patients (20%) had ascites and/or urinoma, and 48 (80%) did not. GA and birth weight were not different in patients with and without extravasation. PUV was suspected from prenatal ultrasound findings in 66.7% of the patients in both groups. Median nadir creatinine was 21 (range, 11-33) μmol/L in boys with ascites/urinoma, and all values were within the age-adjusted reference values. Nadir creatinine was 23 (14-199) μmol/L in boys without extravasation, and it was above the normal range in 14 boys. The incidence of elevated nadir creatinine was significantly different in the two groups (p<0.025). One of the 12 patients with extravasation developed chronic renal failure (CKD 3). In the group of 48 patients without extravasation, 20 (42%) had chronic renal failure grade 2-5, and among these, 5 patients have had a renal transplant (CKD grade 5). The prevalence of CKD grade 2-5 was statistically different in the two groups (p=0.03). These findings are presented in the summary figure. Extravasation of urine was found in 12 of 60 (20%) boys with PUV. These patients had significantly lower prevalence of CKD at the last follow-up than patients without extravasation. This finding is important in prenatal counseling. It also indicates that prenatal decompression of the bladder and upper tract is beneficial in patients with PUV, which is relevant to the discussion of prenatal intervention in these fetuses.

Night-time diuresis pattern in children with and without primary monosymptomatic nocturnal enuresis

Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor overactivity and high arousal thresholds as alternatives. An earlier finding of night-time polyuria in 12% of healthy non-enuretic schoolchildren underscores that excessive night-time diuresis per se is unlikely the major cause of PMNE. The objective of this study was to compare the night-time diuresis pattern in children with and without PMNE and to evaluate the role of night-time polyuria in provoking enuretic episodes in children with PMNE. Night-time diuresis pattern was recorded in 27 children with PMNE, aged 6-15 years, and 29 non-enuretic children, aged 6-13 years. Using a portable ultrasound recorder, the bladder volume was estimated at 15-min intervals for at least three nights with the child sleeping in its own bed at home. The volume of enuretic episodes was controlled using preweighed diapers. All voids were registered by time and volume. Diuresis during night time was estimated from the slope of regression lines fitted to ultrasound recording points. Mean night-time diuresis was calculated from total urine production during the night and time interval from the last void before bedtime to the first morning void. Night-time bladder filling pattern was recorded from 189 nights, giving 149 interpretable patterns for analysis (77 children with PMNE and 72 dry children). The night-time diuresis pattern was similar for children with or without PMNE, showing large variability between different nights of the same child. Most nights displayed a smooth bladder filling at constant low rate, whereas other nights showed an early phase with high diuresis followed by a longer period of low diuresis with no difference between the two groups. Night-time diuresis has been non-invasively monitored in children while asleep in their own beds at home. The pattern of night-time diuresis varies considerably between different nights of the same child, with no obvious differences in any diuresis parameters between children with or without PMNE. Non-enuretic children have similar diuresis pattern and maximal night-time diuresis values as children with PMNE, making it unlikely that PMNE is caused by night-time polyuria per se (Summary figure). Delayed maturation of sleep mechanisms such as decreased arousability or sleep inhibition of the micturition reflex is more likely to be the main etiology for enuresis.

The Role of Optokinetic Nystagmus in Vection Illusion

Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic destructive granulomatous inflammation of the kidney. It was first described in 1916, and is thought to affect 6/1000 cases of pyelonephritis. Its manifestations are varied, and with a limited number of cases in the literature, the optimal diagnosis and management of XGP in the paediatric cohort is still unknown.The medical records of children who were diagnosed and treated for XGP at the current unit during the period 1963–2016, inclusive, were retrospectively reviewed. Information pertaining to each patient was recorded, including: demographic data, past medical history, clinical and biochemical characteristics, diagnostic procedures, treatment methods, histopathologic diagnosis of the removed specimen, and outcome.A total of 66 children with a median age of 4.84 years (range 1.1–14.81), with an M:F ratio 1.35:1 underwent nephrectomy for XGP and had a median follow-up of 7.19 years (range 0.11–17.45). The most common presentations were systemic illness (62.1%), pain (60.6%), urinary tract infections (54.5%) and an abdominal mass (39.4%); pyrexia was present in 53%. Biochemical abnormalities included anaemia (86.3%), thrombocytosis (80.3%) and hypomagnesemia (65.1%). There was an 83.3% concordance between intraoperative cultures and positive mid-stream urines. Index kidneys were significantly larger than the contralateral side (mean 1.32 cm; P = 0.002). Staging of XGP demonstrated extension beyond the kidney in 79% of kidneys. Computed tomography (CT) was performed in 11 cases (Summary figure). Dimercaptosuccinic acid (DMSA) scan showed 0–10% function in 90.47% of cases. Surgical procedures included nephrectomy (n = 63) and partial nephrectomy (n = 3). Perioperative complications included colonic resections (n = 5) and abscess formation in 18%.This is the largest series to date of XGP in a paediatric cohort. XGP should be included in the differential diagnosis of all children presenting with perirenal or psoas abscesses, renal masses and/or non-functioning kidneys with/or without associated urolithiasis. Clinical awareness and a high index of suspicion is required to achieve the correct pre-operative diagnosis and appropriate management.

Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012

Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes.

Influence of BMI in nephrolithiasis in an Appalachian pediatric population: A single-center experience

The prevalence of pediatric nephrolithiasis has increased significantly in the past 20 years. Metabolic abnormalities predisposing adults to nephrolithiasis in obese patients include increased urinary sodium and uric acid excretion as well as low urine pH; however, limited data are available in the pediatric population. The aim was to investigate whether obese pediatric patients presenting with nephrolithiasis have a unique metabolic profile similar to reported findings in obese adults with nephrolithiasis. A retrospective chart review was performed in children aged 1-18 years seen at Kentucky Children's Hospital between 2010 and 2016. Inclusion criteria included all patients with documented stones confirmed by ultrasonography or computed tomography. A total of 111 patient charts were reviewed in the study with a mean age of 11.8±4.2 years. Seventy patients (63%) had a normal BMI and 41 patients (37%) were considered overweight/obese. There was no statistically significant relationship between BMI and stone recurrence. Obese patients had significantly decreased levels of urinary citrate, oxalate, magnesium, and potassium with significant elevations of urinary urea nitrogen, ammonia, and low urine pH compared with normal weight patients (Summary Figure). Several groups have reported on metabolic findings within obese and non-obese pediatric patients. A Turkish study reported increased oxalate excretion and hypocitraturia in obese patients while a Korean study also reported increased rates of hypocitraturia in recurrent stone formers. Similar to these studies, we did find significant differences in citrate within our study population; however, we found significantly lower levels of urinary oxalate in obese patients. The majority of these studies do not report an association with BMI and urine pH although this has been reported in the adult population and our findings support an inverse relationship between body mass index (BMI) and pH. Our group found a higher level of calcium phosphate stones, supporting of Eisner's findings that high BMI is associated with increased supersaturation of calcium phosphate. Limitations of our study include being a single center and retrospective in nature. Our study demonstrates differences in types of stones and urinary metabolites in an obese pediatric population suggestive of different metabolic profiles contributing to stone disease. We report similar association between BMI and urine pH, urinary potassium, and citrate. This study confirmed our primary hypothesis that obese pediatric patients would have a different urinary mineral profile as evidenced by lower levels of citrate and potassium and low urine pH; however, obese patients did not exhibit significantly elevated urinary sodium and uric acid when normalized to weight, as described in the adult population. Our study did not confirm our secondary hypothesis that stone composition would be associated with BMI status or stone recurrence.

The association between continuous antibiotic prophylaxis and UTI from birth until initial postnatal imaging evaluation among newborns with antenatal hydronephrosis

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). 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. 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. 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<0.001). There was no difference in CAP based on sex, insurance, or circumcision status (among 260/365 males with known circumcision status). Overall, seven infants (1.4%) developed UTI prior to imaging: six (1.8%) without CAP vs one (0.64%) with CAP (P=0.44). The median age at UTI was 59 days (range 2-84); among those with UTI, initial imaging occurred significantly later (66 vs 28 days; P=0.001). The propensity score adjusted odds of developing UTI with CAP (vs without) was 0.93 (95% CI 0.10-8.32; P=0.95). The Summary Figure describes the infants with UTI. The incidence of UTI prior to initial neonatal imaging in newborns with AUTD was low. Use of CAP was not associated with UTI incidence after adjusting for UTD severity. Routine use of CAP in newborns with AUTD prior to initial imaging may be of limited benefit in most patients.