The orchestration of gene expression and the editing role of microRNA.

In this short educational communication the ESPU Research Committee presents the role of non-coding RNA and how these can affect gene expression. In particular we discuss the role of microRNA on post transcriptional changes and how these may cause pathological conditions within Pediatric Urology and how microRNA could be useful in future clinical practice.

COVID-19 and research in pediatric urology.

COVID-19 began in December 2019 then spread worldwide. Providers, including pediatric urologists, had to adapt their clinical processes, and many non-covid research activities were suspended. COVID-19 impacts how research is financed, performed, and published, and is itself the subject of intense research. We present current research and publications specifically related to the urinary tract and the pediatric population.

EBM II: How to perform a literature search.

The present article is a second part related to evidence based medicine (EBM) in a series of five by the European society for paediatric urology (ESPU) research committee. It will present the different databases/search engines available to clinicians and researchers and describe strategies to focus the search to one's particular needs. Indeed, databases/search engines used and search strategy should vary according to the goal of the research. If the aim is to address a clinical problem, the search should allow to identify a small number of most pertinent articles (high specificity); if the search is for research purposes, instead, it should ensure no meaningful articles are overlooked (high sensitivity).

Variation in the use of laparoscopy with inguinal hernia repairs in a sample of pediatric patients at children's hospitals.

INTRODUCTION/BACKGROUND: Metachronous contralateral inguinal hernias (MCH) occur in approximately 10% of pediatric patients following unilateral inguinal hernia repairs (UIHR). Laparoscopic evaluation of the contralateral internal ring is a method of identifying high-risk individuals for prophylactic contralateral exploration and repair. OBJECTIVE: The objective of this study was to assess variation in utilization of diagnostic laparoscopy, and report costs associated with the evaluation of a contralateral patent processus vaginalis during hernia repair in pediatric hospitals. STUDY DESIGN: The Pediatric Health Information System database was searched to identify outpatient surgical encounters for pediatric patients with a diagnosis of inguinal hernia during a 1-year period (2014). Records were identified that contained diagnostic codes for unilateral or bilateral inguinal hernia in combination with a procedure code for open hernia repair with or without diagnostic laparoscopy. RESULTS: After exclusions there were 3952 hernia repairs performed at 30 hospitals; median age was 4 years (IQR 1-7), 78.8% were male, and 64.9% Caucasian. Three-quarters (76.7%) had UIHR, 8.6% had unilateral repairs with laparoscopy (UIHRL), 12.2% had bilateral inguinal hernia repairs (BIHR), and 2.4% had bilateral repairs with laparoscopy (BIHRL). Where laparoscopy was used, 78% resulted in a unilateral repair and 22% in a bilateral procedure. The percent of patients undergoing laparoscopy varied from 0 to 57% among hospitals, and 0-100% among surgeons. Pediatric surgeons were more than three times more likely to perform a diagnostic laparoscopy compared with pediatric urologists. Median adjusted costs were $2298 (IQR 1659-2955) for UIHR, $2713 (IQR 1873-3409) for UIHRL, $2752 (IQR 2230-3411) for BIHR, and $2783 (IQR 2233-3453) for BIHRL. Median costs varied over two-fold among hospitals ($1310-4434), and over four-fold among surgeons ($948-5040). DISCUSSION: Data suggested that <10% of patients with clinically unilateral inguinal hernias developed MCH. A negative diagnostic laparoscopy ensured that 0.9-1.31% developed MCH. However, up to 30% of patients underwent contralateral exploration/repair when diagnostic laparoscopy was used. The current study found increased costs associated with the use of laparoscopy, with considerable variation in costs among surgeons and hospitals. These data elucidate competing financial and clinical consequences associated with the use of diagnostic laparoscopy with clinically unilateral hernias. CONCLUSIONS: Variation existed in the use of laparoscopy during inguinal hernia repairs and associated costs within the current sample from children's hospitals in the United States. The additional costs of laparoscopic evaluation must be considered against the clinical utility and therapeutic consequences of identifying individuals with a higher risk of metachronous contralateral inguinal hernia.

Time to resolution: A prospective evaluation from the Society for Fetal Urology hydronephrosis registry.

INTRODUCTION: The resolution rate of prenatal urinary tract dilation (UTD) has been documented in several retrospective studies. The present study analyzed prospective observational registry data, with the aim of determining time to resolution among patients prenatally identified with mild postnatal UTD. MATERIALS AND METHODS: A total of 248 subjects, from four centers, were prospectively enrolled from 2008 to 2015. Exclusion criteria included other anomalies (n = 69), fewer than two ultrasounds, and/or <3 months follow-up (n = 26). Resolution was defined as Outcome A (SFU 0) and Outcome B (SFU 0/1). Fisher's exact test, Mann-Whitney U or Kruskal-Wallis test and Kaplan-Meier were used for analysis. RESULTS/DISCUSSION: The median follow-up for 179 (n = 137 males) subjects was 15 months (IQR 7-24), range 0-56 months. VCUG was performed in 100 (57%) and VUR identified in 15 (15%). There was no association with reflux and resolution (P = 0.72). For resolution assessment (n = 153), lower grades were likely to resolve and demonstrated a higher rate in the Outcome B classification. Time to resolution also favored lower grades, with the majority resolving within 2 years (Figure). Surgical intervention was performed in 14 (8%). It is interesting to note that regardless of grade of UTD, there was no difference in frequency of US or the time that RUS was first performed. Practitioners performed the first RUS of life within a narrow window ranging from 0.27 RUS/month for Grade 1 UTD to 0.30 RUS/month for Grade 4 UTD. It was speculated that this practice pattern occurrence likely reflected the deficiency in knowledge by primary care providers, and identified a potential opportunity for education. The SFU registry substantiates that the vast majority of patients will demonstrate transient UTD and most cases that do not resolve will improve within 2 years of life. This data could be used to further an evidenced-based approach towards the evaluation and management of prenatal UTD, as outlined in the multidisciplinary consensus statement for prenatal urinary tract dilation. CONCLUSIONS: This prospective registry confirms that the majority of prenatal UTD is transient, resolution occurs within the first 3 years of life, and most patients will not need intervention. Redefining SFU 1 as normal increased the resolution rate. A large proportion of patients were not evaluated with a VCUG, therefore impact of VUR could not be determined.

Milestone assessment of minimally invasive surgery in Pediatric Urology fellowship programs.

INTRODUCTION: Minimally invasive surgery has become an important aspect of Pediatric Urology fellowship training. In 2014, the Accreditation Council for Graduate Medical Education published the Pediatric Urology Milestone Project as a metric of fellow proficiency in multiple facets of training, including laparoscopic/robotic procedures. OBJECTIVE: The present study assessed trends in minimally invasive surgery training and utilization of the Milestones among recent Pediatric Urology fellows. STUDY DESIGN: Using an electronic survey instrument, Pediatric Urology fellowship program directors and fellows who completed their clinical year in 2015 were surveyed. Participants were queried regarding familiarity with the Milestone Project, utilization of the Milestones, robotic/laparoscopic case volume and training experience, and perceived competency with robotic/laparoscopic surgery at the start and end of the fellowship clinical year according to Milestone criteria. Responses were accepted between August and November 2015. RESULTS: Surveys were distributed via e-mail to 35 fellows and 30 program directors. Sixteen fellows (46%) and 14 (47%) program directors responded. All fellows reported some robotic experience prior to fellowship, and 69% performed >50 robotic/laparoscopic surgeries during residency. Fellow robotic/laparoscopic case volume varied: three had 1-10 cases (19%), four had 11-20 cases (25%), and nine had >20 cases (56%). Supplementary or robotic training modalities included simulation (9), animal models (6), surgical videos (7), and courses (2). Comparison of beginning and end of fellowship robotic/laparoscopic Milestone assessment (Summary Fig.) revealed scores of <3 in (10) 62% of fellow self-assessments and 10 (75%) of program director assessments. End of training Milestone scores >4 were seen in 12 (75%) of fellow self-assessment and eight (57%) of program director assessments. DISCUSSION: An improvement in robotic/laparoscopic Milestone scores by both fellow self-assessment and program director assessment was observed during the course of training; however, 43% of program directors rated their fellow below the graduation target of a Milestone score of 4. CONCLUSION: The best ways to teach minimally invasive surgery in fellowship training must be critically considered.

Trends in treatment and in-hospital mortality for neonates with congenital diaphragmatic hernia.

OBJECTIVE: We performed a retrospective cohort study in order to examine recent trends in use of post-partum treatments and in-hospital mortality for congenital diaphragmatic hernia (CDH). STUDY DESIGN: Included were infants with CDH, born in 2003 to 2012 and hospitalized at ⩽7 days of age at one of 33 United States tertiary referral children's hospitals with extracorporeal membrane oxygenation (ECMO) programs. In-hospital mortality as well as use of ECMO, surfactant and a variety of vasodilators were examined for trends during the study period. RESULT: Inclusion criteria were met by 3123 infants with CDH. Among 2423 term or near-term infants, odds of death decreased annually for those with isolated or complex CDH. For 700 premature or low-birth weight infants with CDH, in-hospital mortality did not change. Among treatments for CDH, increasing with time in the study cohort were use of milrinone and sildenafil individually, and use of multiple vasodilators during the hospitalization. CONCLUSION: Survival improved in large subgroups of term or near-term infants with CDH in this 10-year multicenter cohort, temporally associated with increasing use of multiple vasodilators. Use of vasodilators for infants with CDH is increasing despite a lack of evidence supporting efficacy or safety. Prospective research is needed to clarify specific causal effects contributing to improving survival in these infants.

Objective pain assessment after ureteral reimplantation: comparison of open versus robotic approach.

INTRODUCTION: While open ureteral reimplantation is the gold standard of surgical intervention for vesicoureteral reflux (VUR), minimally invasive approaches offer the potential benefits of decreased postoperative pain, improved cosmesis, and shorter hospital stay and convalescence. Studies comparing open and minimally invasive surgery with respect to postoperative pain in children have been inconclusive. OBJECTIVE: We sought to compare postoperative pain in children undergoing open versus robotic ureteral reimplantation by using age-appropriate, validated pain assessment scales. METHODS: A prospective cohort of all patients enrolled in an Institutional Review Board-approved VUR surgery registry between July 2010 and February 2013 was analyzed. Patients who underwent endoscopic treatment or who received caudal or epidural anesthesia were excluded. Age-appropriate, validated pain scales ranging from 0 to 10 were utilized for pain assessment. Pain scores and narcotic doses administered on the first postoperative day were analyzed. RESULTS: Of the 34 subjects included, 11 underwent open intravesical reimplantation, while 23 patients underwent robotic extravesical reimplantation. Table 1 displays patient characteristics and results of pain assessment. Robotic surgery was associated with lower narcotic requirement compared to open surgery (P < 0.05). The difference in pain scores between the two cohorts approached, but did not reach, statistical significance (P = 0.12). However, the percentage of patients with mild or no pain (57% robotic, 27% open) versus severe pain (9% robotic, 45% open) was notably different between the two cohorts. DISCUSSION: Previous studies addressing the effect of surgical modality on pediatric postoperative pain are limited by their reliance on narcotic administration as an indirect surrogate for measuring pain. In the present study, postoperative pain was assessed with narcotic requirements and consistently collected validated pain scores, which more accurately reflect a patient's perceived pain. Although there was no significant difference in subjective pain scores between patients undergoing open versus robotic reimplantation, the percentage of patients with mild or no pain (57% robotic, 27% open) versus severe pain (9% robotic, 45% open) was notably different between the two cohorts. This study was limited by a lack of randomization as well as small sample size, which did not allow for age sub-group analysis or small differences to be statistically significant. CONCLUSIONS: In the present study, robotic ureteral reimplantation was associated with lower narcotic requirement compared to open surgery, and lower intensity of postoperative pain according to a direct pain assessment tool. Larger sample sizes are necessary to strengthen statistical comparisons.