Development of a Wound-Healing Protocol for In Vitro Evaluation of Urothelial Cell Growth.

Urethral healing is plagued by strictures, impacting quality of life and medical costs. Various growth factors (GFs) have shown promise as therapeutic approaches to improve healing, but there is no protocol for in vitro comparison between GFs. This study focuses the development of a biomimetic in vitro urothelial healing assay designed to mimic early in vivo healing, followed by an evaluation of urothelial cell growth in response to GFs. METHODS: Wound-healing assays were developed with human urothelial cells and used to compared six GFs (EGF, FGF-2, IGF-1, PDGF, TGF-ß1, and VEGF) at three concentrations (1 ng/mL, 10 ng/mL, and 100 ng/mL) over a 48 h period. A commercial GF-containing medium (EGF, TGF-α, KGF, and Extract P) and a GF-free medium were used as controls. RESULTS: There was a statistically significant increase in cell growth for IGF-1 at 10 and 100 ng/mL compared to both controls (p < 0.05). There was a statistically significant increase in cell growth for EGF at all concentrations compared to the GF-free medium control (p < 0.05). CONCLUSION: This study shows the development of a clinically relevant wound-healing assay to evaluate urothelial cell growth. It is the first to compare GFs for future use in reconstructive techniques to improve urethral healing.

Do the materials matter? A review of the literature and analysis of the materials properties of urethral stents for hypospadias repair.

INTRODUCTION: Despite the prevalence of hypospadias surgery and the common use of postoperative urethral stents, there has been no evaluation of the material properties of common stents. Our study sets out to close this gap with a literature review of recent publications comparing outcomes after hypospadias surgery for different urethral stent types and an evaluation of the material properties of four common urethral stents. STUDY DESIGN: A review of the English language literature from 2011 to 2021 was performed. Thermal analysis and mechanical analysis of the Zaontz Urethral Stent, the Firlit-Kluge Urethral Stent, the Koyle Diaper Stent, and the Bard Premature Infant Feeding Tube was also undertaken. RESULTS: Out of 165 papers, four met inclusion criteria. There was limited research on this topic, and no significant evidence that different stent materials impacted surgical complication rates. One study found improved comfort with the Zaontz stent, and another found a reduction emergency room visits with the Koyle stent. Using a foley balloon was associated with increased fistula rates, though this was likely due to the balloon design and not the material. Analysis of stents shows that all four are rubbery polymers at body temperature (Summary Table). The Zaontz and Koyle stents are thermoplastic elastomers with strong melting transitions above body temperature, but the Firlit-Kluge stent is amorphous at 37 °C and is likely covalently cross-linked to generate the network. The Bard feeding tube was the stiffest, with a Young's Modulus of 14.0 ± 0.78 (compared to 4.12 ± 0.56 for Zaontz, 4.92 ± 0.63 for Firlit-Kluge, and 4.09 ± 0.49 for Koyle). The Bard Feeding Tube is also the least extensible, fracturing at just over 300% strain compared to the other stents that can be stretched to greater than 2000% strain before fracture. Cyclic deformation studies demonstrate that the Zaontz, Firlit-Kluge, and Koyle stents are able to stretch and recover their shape more completely, a finding determined by the lower amount of plastic deformation those stents display compared to the Bard Feeding Tube. DISCUSSION: While there is little information associating urethral stent type with outcomes after hypospadias surgery, material properties may account for findings of prior studies. Stiffer stents may contribute to decreased postoperative comfort, while a stent that is too soft and extensible may have issues with dislodgement, kinking and breaking. CONCLUSION: This study provides the foundation for future work optimizing urethral stents, designing support for regenerative medicine applications, and improving hypospadias outcomes.

Contemporary Management of Urinary Tract Infections in Children.

Purpose of Review: Urinary tract infection (UTI) in children is a major source of office visits and healthcare expenditure. Research into the diagnosis, treatment, and prophylaxis of UTI has evolved over the past 10 years. The development of new imaging techniques and UTI screening tools has improved our diagnostic accuracy tremendously. Identifying who to treat is imperative as the increase in multi-drug-resistant organisms has emphasized the need for antibiotic stewardship. This review covers the contemporary management of children with UTI and the data-driven paradigm shifts that have been implemented into clinical practice. Recent Findings: With recent data illustrating the self-limiting nature and low prevalence of clinically significant vesicoureteral reflux (VUR), investigational imaging in children has become increasingly less frequent. Contrast-enhanced voiding urosonogram (CEVUS) has emerged as a useful diagnostic tool, as it can provide accurate detection of VUR without the need of radiation. The urinary and intestinal microbiomes are being investigated as potential therapeutic drug targets, as children with recurrent UTIs have significant alterations in bacterial proliferation. Use of adjunctive corticosteroids in children with pyelonephritis may decrease the risk of renal scarring and progressive renal insufficiency. The development of a vaccine against an antigen present on Escherichia coli may change the way we treat children with recurrent UTIs. Summary: The American Academy of Pediatrics defines a UTI as the presence of at least 50,000 CFU/mL of a single uropathogen obtained by bladder catheterization with a dipstick urinalysis positive for leukocyte esterase (LE) or WBC present on urine microscopy. UTIs are more common in females, with uncircumcised males having the highest risk in the first year of life. E. coli is the most frequently cultured organism in UTI diagnoses and multi-drug-resistant strains are becoming more common. Diagnosis should be confirmed with an uncontaminated urine specimen, obtained from mid-stream collection, bladder catheterization, or suprapubic aspiration. Patients meeting criteria for imaging should undergo a renal and bladder ultrasound, with further investigational imaging based on results of ultrasound or clinical history. Continuous antibiotic prophylaxis is controversial; however, evidence shows patients with high-grade VUR and bladder and bowel dysfunction retain the most benefit. Open surgical repair of reflux is the gold standard for patients who fail medical management with endoscopic approaches available for select populations.

Tissue Engineering Opportunities for Vaginal Replacement in a Pediatric Population.

Treatment for children born with vaginal agenesis remains difficult, without a clear gold standard for tissue replacement. An autologous-engineered vaginal replacement would significantly improve quality of life for people born with this condition. The aim of this study was to critically review literature on the current state of tissue engineering for vaginal reconstruction in a pediatric population. An electronic literature search was conducted using PubMed for articles describing pediatric vaginal tissue engineering from January 2003 to December 2020. Nine studies met inclusion criteria and were reviewed. The model, methods, cell type and source, scaffold type, and time of analysis and evaluation were compared. Three studies used in vitro and six used an in vivo design. Of the six in vivo studies, one was able to investigate autologous vaginal epithelial cells in human clinical trials. This review discusses the current knowledge and progress of vaginal tissue engineered replacements that can potentially be used as a basis for both future preclinical animal and clinical human studies. Impact statement The current methods of treatment for congenital vaginal anomalies leave room for improvement. The state of tissue engineering may provide a method to improve the surgical interventions provided for these patients, in hopes of providing increased vaginal functionally and quality of life.

Harnessing the epic electronic medical record to track indwelling ureteral stents in a pediatric population.

INTRODUCTION: Retention of indwelling ureteral stents due to loss to follow-up can result in significant harm to patients, often requiring multiple trips to the operating room. Despite widespread use of electronic medical records, there are few standardized options for urologists to track ureteral stents and no data on the rate of retained stents in a pediatric population. OBJECTIVE: This pilot quality improvement project aims to: 1) develop a simple process to track indwelling ureteral stents using the Epic electronic medical record and 2) determine the incidence of forgotten stents in a pediatric population. METHODS: We identified that operating room staff scan a barcode for ureteral stents at the time of surgery to log the stent as "Implanted" in the patient's medical record. The stent can later be marked as "Explanted" at the time of removal. A report was designed within Epic to identify all patients with a ureteral stent implanted from April 2014 to June 2019 at our hospital. We reviewed the records of patients whose stents had never been marked as "Explanted" to determine if any had a retained stent. A workflow was then designed to ensure staff would mark stents as "Explanted" at the time of removal and to periodically run the report within Epic to ensure that all patients with ureteral stents in place have appropriate follow-up. RESULTS: Our report identified 152 ureteral stents with a status of "Implanted". 3 patients did not have evidence of stent removal documented in their medical record. Follow up with these patients revealed stent removal at an outside location. DISCUSSION: Current approaches to stent tracking are laborious with limitations to adherence. The Epic software directly incorporates stent tracking into the individual patient chart allowing for easy implementation and follow up. Our study revealed no retained stents in our pediatric population. CONCLUSIONS: All patients with ureteral stents placed at a single institution over a 5-year period were easily identified using an automated Epic report. Through this report, we will prevent morbidity associated with stent retention. This technique could easily be implemented at other hospital systems that use Epic, and similar reporting tools could be designed within other electronic medical record systems. The incidence of ureteral stent retention in the pediatric population is likely significantly lower than for their adult counterparts.

The Use of Social Media in Pediatric Urology-Forging New Paths or Crossing Boundaries?

PURPOSE OF REVIEW: There has been a remarkable change in how people connect, access, and share professional and medical information over social media. This perspective article describes opportunities, potential pitfalls, and guidelines for social media use by pediatric urology providers. RECENT FINDINGS: Pediatric urologists have effectively used social media to connect and share expertise, augment scientific conference participation, promote themselves and their research, disseminate guidelines and best practices, participate in virtual journal clubs, and engage with patients and their families. Information shared over social media is not protected by copyright law, not confidential, not regulated, permanent, and subjected to public domain and scrutiny. Despite these potential pitfalls, social media is a useful tool if best practices are observed and online communication adheres to professional guidelines and organizational policy. Social media use in healthcare is here to stay and pediatric urologists have online visibility whether or not they choose to actively participate. Despite new legal, ethical, and professional considerations that social media introduces, a well-executed social media presence provides pediatric urologists a wealth of new opportunities for networking, research, and disseminating high-quality medical information online.

Predicting anatomical urological abnormalities in children who present with their first urinary tract infection.

OBJECTIVES: Classically, presence of fever≥38.0°C is used to distinguish pyelonephritis from cystitis. We analyzed whether this is an appropriate marker to initiate further workup and whether temperature is correlated with urological abnormalities and further surgical or pharmacological intervention. METHODS: Children who presented for their first workup of urinary tract infection between October 1, 2008, and September 30, 2009 were retrospectively selected from our institution. Demographics and clinical details were correlated with the diagnosis of urological abnormalities and requirement for intervention. RESULTS: Age was the most important variable to predict urological abnormalities. The temperature value of 38.3°C maximized the balance between sensitivity (90%) and specificity (46%) for predicting the need to intervene and the presence of anatomical urological abnormalities. CONCLUSION: Young age (≤2 years) and temperature are the best factors to predict further intervention and urological abnormalities, with a temperature value of 38.3°C being a better predictive value than the currently used 38.0°C.

A novel method of evaluating ureteropelvic junction obstruction: dynamic near infrared fluorescence imaging compared to standard modalities to assess urinary obstruction in a swine model.

PURPOSE: Dynamic near infrared fluorescence imaging of the urinary tract provides a promising way to diagnose ureteropelvic junction obstruction. Initial studies demonstrated the ability to visualize urine flow and peristalsis in great detail. We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic junction obstruction, renal involvement and the anatomical detail provided compared to conventional imaging modalities. MATERIALS AND METHODS: Ten swine underwent partial or complete unilateral ureteral obstruction. Groups were survived for the short or the long term. Imaging was performed with mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic junction obstruction were developed for magnetic resonance urogram and near infrared imaging. Physicians and medical students graded ureteropelvic junction obstruction based on magnetic resonance urogram and near infrared imaging results. RESULTS: Markers of vascular and urinary dynamics were quantitatively consistent among control renal units. The same markers were abnormal in obstructed renal units with significantly different times of renal phase peak, start of pelvic phase and start of renal uptake. Such parameters were consistent with those obtained with mercaptoacetyltriglycine diuretic renography. Near infrared imaging provided live imaging of urinary flow, which was helpful in identifying the area of obstruction for surgical planning. Physicians and medical students categorized the degree of obstruction appropriately for fluorescence imaging and magnetic resonance urogram. CONCLUSIONS: Near infrared imaging offers a feasible way to obtain live, dynamic images of urine flow and ureteral peristalsis. Qualitative and quantitative parameters were comparable to those of conventional imaging. Findings support fluorescence imaging as an accurate, easy to use method of diagnosing ureteropelvic junction obstruction.

A comparative direct cost analysis of pediatric urologic robot-assisted laparoscopic surgery versus open surgery: could robot-assisted surgery be less expensive?

BACKGROUND AND PURPOSE: Cost in healthcare is an increasing and justifiable concern that impacts decisions about the introduction of new devices such as the da Vinci(®) surgical robot. Because equipment expenses represent only a portion of overall medical costs, we set out to make more specific cost comparisons between open and robot-assisted laparoscopic surgery. MATERIALS AND METHODS: We performed a retrospective, observational, matched cohort study of 146 pediatric patients undergoing either open or robot-assisted laparoscopic urologic surgery from October 2004 to September 2009 at a single institution. Patients were matched based on surgery type, age, and fiscal year. Direct internal costs from the institution were used to compare the two surgery types across several procedures. RESULTS: Robot-assisted surgery direct costs were 11.9% (P=0.03) lower than open surgery. This cost difference was primarily because of the difference in hospital length of stay between patients undergoing open vs robot-assisted surgery (3.8 vs 1.6 days, P<0.001). Maintenance fees and equipment expenses were the primary contributors to robotic surgery costs, while open surgery costs were affected most by room and board expenses. When estimates of the indirect costs of robot purchase and maintenance were included, open surgery had a lower total cost. There were no differences in follow-up times or complication rates. CONCLUSIONS: Direct costs for robot-assisted surgery were significantly lower than equivalent open surgery. Factors reducing robot-assisted surgery costs included: A consistent and trained robotic surgery team, an extensive history of performing urologic robotic surgery, selection of patients for robotic surgery who otherwise would have had longer hospital stays after open surgery, and selection of procedures without a laparoscopic alternative. The high indirect costs of robot purchase and maintenance remain major factors, but could be overcome by high surgical volume and reduced prices as competitors enter the market.

Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis.

UNLABELLED: Study Type - Aetiology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Genetic linkage to distinguish loci for VUR has been previously described in several autosomal chromosomes. Although there are numerous explanations for the dissimilar findings, e.g. multifactorial etiology of VUR and hereditary miscellany among studied populations, clinical diversity between males and females may indicate a central gender-specific genetic susceptibility. Early studies suggested the presence of modified VUR gene(s) on the X-chromosome, accounting for the higher incidence of this disorder among female members in the pedigrees studied. On the other hand male-to-male transmission and a higher ratio of females to males argued against X-linked inheritance. More recently, additional chromosomal regions (i.e. chromosomes 1-7, 10-13, and 18-22) have been identified for VUR by using single nucleotide polymorphism-genome-wide linkage analysis. This is the first study to show that there is autosomal difference in VUR expression in males and females. This genotype variability may be the basis for the clinical differences between genders in children with VUR. OBJECTIVE: To assess gender-specific genetic differences in the susceptibility loci for vesico-ureteric reflux (VUR) in families who have two or more affected children. PATIENTS AND METHODS: A genome-wide linkage analysis of VUR with high-density single nucleotide polymorphisms was conducted in 98 families with two or more affected children. A total of 221 affected offspring (123 sibling pairs) were included in the analysis. Genomic DNA was extracted from blood or saliva from all the patients. Data was stratified and analysed according to clinical presentation and gender of the proband and affected siblings. RESULTS: Using the affected sib-pair method, statistically significant peaks were found on chromosomes 1 (logarithm of odds, base10 [LOD] 4.4) and 5 (LOD 3.7) in males and on chromosomes 3 (LOD 3.5), 13 (LOD 4.5), and 15 (LOD 3.4) in females. CONCLUSION: This genotype variability might be the basis for the clinical differences between genders in children with VUR. Our data might be the first step to understanding the genetic background behind the gender-specific differences of VUR and more clearly defining the genetically different subgroups of VUR.