Identification of novel genes expressed during metanephric induction through single-cell library screening

Identification of novel genes expressed during metanephric induction through single-cell library screening.BackgroundDevelopment of the mature kidney is dependent on a series of inductive events between a portion of the epithelial bud at the distal end of the nephric duct and a neighboring domain of committed metanephric mesenchyme. Several genes have been identified to date that are critical in the inductive process. For example, the deletion of Bmp7 from the mouse genome results in dysgenesis or agenesis of the kidney. These findings suggest that Bmp7 controls the expression of genes important for nephrogenesis, but the identity of these genes has remained largely undetermined.MethodsSingle cells were isolated from mouse metanephric mesenchyme during the time of induction (between E11.0 and E11.5) and cDNA libraries constructed from induced and uninduced tissue. Subtractive hybridization was performed to isolate genes that were expressed during E11.5 but not E11.0.ResultsUsing this approach, we identified eight previously known genes, three of which were known to be involved in metanephric induction, thus validating our approach, and nine novel genes. Eight of these genes were completely novel, whereas one was similar to a member of the yeast Anaphase Promoting Complex.ConclusionsThrough subtractive hybridization of mouse E11.0 and E11.5 metanephric mesenchyme single-cell cDNA libraries, we have identified novel genes that are candidates for involvement in nephrogenesis through their up-regulation during the inductive process

Vesicoamniotic Shunting Improves Outcomes in a Subset of Prune Belly Syndrome Patients at a Single Tertiary Center

Objective: Review outcomes of Prune Belly Syndrome (PBS) with the hypothesis that contemporary management improves mortality.Methods: A retrospective chart review of inpatient and outpatient PBS patients referred between 2000 and 2018 was conducted to assess outcomes at our institution. Data collected included age at diagnosis, concomitant medical conditions, imaging, operative management, length of follow-up, and renal function.Results: Forty-five PBS patients presented during these 18 years. Prenatal diagnoses were made in 17 (39%); 65% of these patients underwent prenatal intervention. The remaining patients were diagnosed in the infant period (20, 44%) or after 1 year of age (8, 18%). Twelve patients died from cardiopulmonary complications in the neonatal period; the neonatal mortality rate was 27%. The mean follow-up among patients surviving the neonatal period was 84 months. Forty-two patients had at least one renal ultrasound (RUS); of the 30 patients with NICU RUSs, 26 (89%) had hydronephrosis and/or ureterectasis. Of the 39 patients who underwent voiding cystourethrogram (VCUG), 28 (62%) demonstrated VUR. Fifty-nine percent had respiratory distress. Nine patients (20%) were oxygen-dependent by completion of follow up. Thirty-eight patients (84%) had other congenital malformations including genitourinary (GU) 67%, gastrointestinal (GI) 52%, and cardiac 48%. Sixteen patients (36%) had chronic kidney disease (CKD) of at least stage 3; three patients (7%) had received renal transplants. Eighty-four percent of patients had at least one surgery (mean 3.4, range 0–6). The most common was orchiopexy (71%). The next most common surgeries were vesicostomy (39%), ureteral reimplants (32%), abdominoplasty (29%), nephrectomy (25%), and appendicovesicostomy (21%). After stratifying patients according to Woodard classification, a trend for 12% improvement in mortality after VAS was noted in the Woodard Classification 1 cohort.Conclusions: PBS patients frequently have multiple congenital anomalies. Pulmonary complications are prevalent in the neonate while CKD (36%) is prevalent during late childhood. The risk of CKD increased significantly with the presence of other congenital anomalies in our cohort. Mortality in childhood is most common in infancy and may be as low as 27%. Contemporary management of PBS, including prenatal interventions, reduced the neonatal mortality rate in a subset of our cohort

Evaluating Natural History and Follow Up Strategies for Non-obstructive Urolithiasis in Pediatric Population

Objective: While small non-obstructive stones in the adult population are usually observed with minimal follow-up, the same guidelines for management in the pediatric population have not been well-studied. We evaluate the clinical outcomes of small non-obstructing kidney stones in the pediatric population to better define the natural history of the disease.Methods: In this IRB-approved retrospective study, patients with a diagnosis of kidney stones from January 2011 to March 2017 were identified using ICD9 and ICD10 codes. Patients with ureteral stones, obstruction, or stones >5 mm in size were excluded. Patients with no follow-up after initial imaging were also excluded. Patients with a history of stones or prior stone interventions were included in our population. Frequency of follow-up ultrasounds while on observation were noted and any ER visits, stone passage episodes, infections, and surgical interventions were documented.Results: Over the 6-year study period, 106 patients with non-obstructing kidney stones were identified. The average age at diagnosis was 12.5 years and the average stone size was 3.6 mm. Average follow-up was 17 months. About half of the patients had spontaneous passage of stones (54/106) at an average time of 13 months after diagnosis. Stone location did not correlate with spontaneous passage rates. Only 6/106 (5.7%) patients required stone surgery with ureteroscopy and/or PCNL at an average time of 12 months after initial diagnosis. The indication for surgery in all 6 cases was pain. 17/106 (16%) patients developed febrile UTIs and a total of 43 ER visits for stone-related issues were noted, but no patients required urgent intervention for an infected obstructing stone. Median interval for follow-up was every 6 months with renal ultrasounds, which then was prolonged to annual follow up in most cases.Conclusions: The observation of pediatric patients with small non-obstructing stones is safe with no episodes of acute obstructive pyelonephritis occurring in these patients. The sole indication for intervention in our patient population was pain, which suggests that routine follow-up ultrasounds may not be necessary for the follow-up of pediatric non-obstructive renal stones ≤5 mm in size

Common Problems in Pediatric Urology

xviii, 485 p. : il.; 21 cm

Surgical antibiotic practices among pediatric urologists in the United States

Purpose: We hypothesized that there are practice variations in the use of surgical antibiotics by pediatric urologists in the United States. Materials and methods: A 31-question online survey was distributed to members of the Society of Pediatric Urology. The questionnaire examined physician preferences for surgical antibiotic use, including indications, antibiotic selection, timing of administration, and duration. Results: 189 pediatric urologists responded to the survey. \u3e85% of responders give antibiotics before open pyeloplasty, after hypospadias repair (when a urethral catheter is left in place), or perioperative or postoperative antibiotics for open neoureterocystostomy or bladder reconstructive surgery. \u3e90% of responders do not give postoperative antibiotics to children who have undergone circumcisions, simple chordee repairs, herniorrhapies, or hydrocelectomies. For all other open, laparoscopic, and endoscopic operations, use of antibiotics varied significantly. Diverse opinions exist regarding antibiotic use, including the importance of costs, potential adverse reactions, reduction in infection risk, and antibiotic resistance. There are major differences in gentamicin dosing and timing of administration of perioperative antibiotics. Conclusions: Perioperative and postoperative antibiotics are widely used by pediatric urologists. However, there is significant practice variation in surgical antibiotic administration with regards to most areas of pediatric urology, in particular laparoscopic, endoscopic and hypospadias surgery. © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved

Ex-premature infant boys with hypospadias are similar in size to age-matched, ex-premature infant boys without hypospadias

Objective: Studies have postulated that hypospadias, prematurity, and low birth weight are linked by defects in androgen signaling. To determine whether premature, hypospadiac boys are small and remain so, we compared their size at birth and at hypospadias repair to premature boys who underwent post-neonatal circumcision. Methods: We identified premature boys admitted to Texas Children\u27s Hospital who underwent either hypospadias repair or circumcision after 4 months of age. Age, weight, and height at birth and surgery were recorded. Results: Fifty-four boys had hypospadias and 34 did not. For hypospadiac boys, the mean birth weight and age, height, and weight at surgery were lower than for boys without hypospadias. More importantly, length-for-age and weight-for-age percentiles were also lower for hypospadiac boys. When subset analysis was performed on boys younger than 2 years at surgery, however, there were no significant differences in height or weight between hypospadiac and non-hypospadiac boys. Conclusion: Our series suggests that premature, hypospadiac boys are born smaller than age-matched, non-hypospadiac controls. However, there were no age-corrected size differences between hypospadiac and non-hypospadiac boys at surgery. This implies that hypospadiac boys exhibit post-neonatal \u27rebound\u27 growth. Global growth deficits, if any, do not persist in hypospadiac boys. © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved

Factors associated with delayed treatment of acute testicular torsion - Do demographics or interhospital transfer matter?

Purpose: Testicular torsion is a true urological emergency. We determined whether a delay in treatment due to hospital transfer or socioeconomic factors would impact the orchiectomy rate in children with this condition. Materials and Methods: We retrospectively evaluated the records of boys seen at a single institution emergency department who proceeded to surgery for a diagnosis of acute testicular torsion from 2003 to 2008. Charts were reviewed for transfer status, symptom duration, race, insurance presence or absence and distance from the hospital. Orchiectomy specimens were evaluated for histological confirmation of nonviability. Results: We reviewed 97 records. The orchiectomy rate in patients who were vs were not transferred to the emergency department was 47.8% vs 68.9%, respectively (p = 0.07). Symptom duration was greater in the orchiectomy group with a mean difference of 47.9 hours (p \u3c0.01). The mean transfer delay was 1 hour 15 minutes longer in the orchiectomy group (p = 0.01). Boys who underwent orchiectomy were 2.2 years younger than those who avoided orchiectomy (p = 0.01). Multivariate analysis showed that symptom duration and distance from the hospital were the strongest predictors of orchiectomy. Conclusions: Data suggest that torsion is a time dependent event and factors that delay time to treatment lead to poorer outcomes. These factors include distance from the hospital and the time delay associated with hospital transfer. © 2010 American Urological Association Education and Research, Inc

Cross-sectional evaluation of parental decision making factors for vesicoureteral reflux management in children

Purpose: Parental decision making in children with vesicoureteral reflux has potentially become more complex with the evolution of ethnic diversity in the United States the Internet the publication of contradictory clinical data and the emergence of minimally invasive surgery. We performed a cross-sectional study of parental management for pediatric vesicoureteral reflux. Materials and Methods: We administered a 26-item questionnaire to parents of children with vesicoureteral reflux seen at Texas Children\u27s Hospital urology offices or undergoing antireflux surgery at that institution. Univariate and multivariate analysis was done on patient disease characteristics, demographics, predicted reflux duration, surgery success rate, antibiotic cessation, complication risk, financial considerations, urologist recommendations, Internet information, friend recommendations, and postoperative voiding cystourethrography, renal ultrasound and recovery. Results: Enrolled in the study were 15 boys and 49 girls with a mean age of 3.5 years and a mean reflux grade of 2.8. Of the cases 37 were bilateral. Parents chose endoscopic treatment in 38 children, open ureteroneocystostomy in 9, antibiotic prophylaxis in 14 and observation without antibiotics in 3. Univariate analysis suggested that Hispanic parents rated ultrasound and financial considerations as more important than white parents (p \u3c0.05). Multivariate analysis revealed that differences seen on univariate analysis may have been due to an association between race and income. Finally, 93.6% of parents rated urologist opinion as very or extremely important. Conclusions: Data indicate that the parents of our patients highly value the opinion of the pediatric urologist when choosing treatment for their children with vesicoureteral reflux. Despite social changes the physician-parental relationship remains critical. Differences in parental decision making may be linked to associations between race and income. © 2010 American Urological Association Education and Research, Inc