Clay modeling as a learning tool for medical trainees in urology: a narrative review and pilot study.

Background and Objective: Coronavirus disease 2019 (COVID-19) necessitated a transition to virtual education which limits hands-on opportunities and student engagement. To adapt, a pilot study investigating clay modeling as an alternative educational tool for medical students was incorporated in a virtual and in-person sub-internship for prospective urology applicants. We aim to review the literature supporting the use of clay modeling in medical education as well as describe our experience with the activity as a way to engage trainees and evaluate early surgical skills. Methods: The current literature on clay modeling in medical and early surgical education was reviewed using multiple search queries in PubMed. A total of thirteen publications were identified and analyzed, with zero articles specifically discussing urological anatomy or surgery. The pilot study was conducted through the traditional in-person sub-internship as well as through a novel virtual sub-internship at a single academic U.S. Urology residency program. Students were instructed to create a three-dimensional model of a genitourinary organ using modeling clay. Anonymized surveys were collected. Responses of virtual and in-person students were compared. Key Content and Findings: Clay modeling has been shown in the literature to be beneficial in medical and early surgical education through the use of active learning. Twenty-five total virtual (N=6) and in-person (N=19) students participated in the clay modeling activity. Survey ratings were mixed, with 100% positive responses amongst the virtual group in the areas of "relevance" and "creatively challenging" compared to the in-person cohort, 31.6% of whom responded positively to "relevance" and 47.4% for "creatively challenging" respectively. Overall, students responded positively for the exercise being "creatively challenging" (n=15, 60%) and "enjoyable" (n=16, 64%). Positive results echoed the student perspectives described in the current literature on clay modeling. Conclusions: Clay modeling has previously been used in the in-person classroom setting as a learning supplement or replacement for dissection classes but has not been previously described for use in the virtual learning environment or within the field of Urology. With ongoing need to develop novel teaching modalities, clay modeling may be a unique tool to enhance learning, and evaluate technical skill, and boost engagement for medical trainees.

Feasibility of Enhanced Recovery After Surgery (ERAS) implementation in Pediatric Urology: Pilot-phase outcomes of a prospective, multi-center study.

INTRODUCTION/BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a fundamental shift in perioperative care that has consistently demonstrated an improved outcome for a wide variety of surgeries in adults but has only limited evidence in the pediatric population. OBJECTIVE: We aimed to assess the success with and barriers to implementation of ERAS in a prospective, multi-center study on patients undergoing complex lower urinary tract reconstruction. STUDY DESIGN: Centers were directed to implement an ERAS protocol using a multidisciplinary team and quality improvement methodologies. Providers completed pre- and post-pilot surveys. An audit committee met after enrolling the first 5 patients at each center. Pilot-phase outcomes included enrollment of ≥2 patients in the first 6 months of enrollment, completion of 90 days of follow-up, identification of barriers to implementation, and protocol adherence. RESULTS: A total of 40 patients were enrolled across 8 centers. The median age at surgery was 10.3 years (IQR 6.4-12.5). Sixty five percent had a diagnosis of myelomeningocele, and 33 % had a ventriculoperitoneal shunt. A bladder augmentation was performed in 70 %, Mitrofanoff appendicovesicostomy in 52 %, Monti ileovesicostomy in 15 %, and antegrade continence enema channel in 38 %. The most commonly perceived barriers to implementation on the pre-pilot survey were "difficulty initiating and maintaining compliance with care pathway" in 51 % followed by a "lack of time, money, or clinical resources" in 36 %. The pre-pilot study experience, implementation, and pilot-phase outcomes are provided in the Table. All primary and secondary outcomes were achieved. DISCUSSION: The findings of the present study were similar to several small comparative studies with regard to the importance of a multidisciplinary team, strong leadership, and continuous audit for successful implementation of ERAS. Similar barriers were also encountered to other studies, which primarily related to a lack of administrative support, leadership, and buy-in from other services. The limitations of the present study included a relatively small heterogeneous cohort and absence of a comparative group, which will be addressed in the larger exploratory phase of the trial. The findings may also not be generaziable due to the need for sustainable processes that were unique to each center as well as an absence of adequate volume or resources at smaller centers. CONCLUSIONS: ERAS was successfully implemented for complex lower urinary tract reconstruction across 8 centers through a multidisciplinary team, structured approach based on the local context, and focus on a continuous audit.

Evaluating the role for regional analgesia in children with spina bifida: a retrospective observational study comparing the efficacy of regional versus systemic analgesia protocols following major urological surgery.

INTRODUCTION: Regional techniques are a key component of multimodal analgesia and help decrease opioid use perioperatively, but some techniques may not be suitable for all patients, such as those with spina bifida. We hypothesized peripheral regional catheters would reduce postoperative opioid use compared with no regional analgesia without increasing pain scores in pediatric patients with spina bifida undergoing major urological surgery. METHODS: A retrospective review of a multicenter database established for the study of enhanced recovery after surgery was performed of patients from 2009 to 2021 who underwent bladder augmentation or creation of catheterizable channels. Patients without spina bifida and those receiving epidural analgesia were excluded. Opioids were converted into morphine equivalents and normalized to patient weight. RESULTS: 158 patients with pediatric spina bifida from 7 centers were included, including 87 with and 71 without regional catheters. There were no differences in baseline patient factors. Anesthesia setup increased from median 40 min (IQR 34-51) for no regional to 64 min (IQR 40-97) for regional catheters (p<0.01). The regional catheter group had lower median intraoperative opioid usage (0.24 vs 0.80 mg/kg morphine equivalents, p<0.01) as well as lower in-hospital postoperative opioid usage (0.05 vs 0.23 mg/kg/day morphine equivalents, p<0.01). Pain scores were not higher in the regional catheters group. DISCUSSION: Continuous regional analgesia following major urological surgery in children with spina bifida was associated with a 70% intraoperative and 78% postoperative reduction in opioids without higher pain scores. This approach should be considered for similar surgical interventions in this population. TRIAL REGISTRATION NUMBER: NCT03245242.

Upper pole pathologies in duplex kidneys: an analysis of predictive factors for surgery and urinary tract infections from the Mid-Atlantic Pediatric Academic Consortium.

BACKGROUND/OBJECTIVE: While there is significant data on the natural history and outcomes for prenatal hydronephrosis in simplex kidneys, duplex kidneys tend to be less studied. Management can be quite variable based on provider preference. We aimed to describe practice patterns from several tertiary academic institutions, identify clinical predictors for surgical intervention and urinary tract infection (UTI) for upper pole pathology, and demonstrate the natural history of lower pole vesicoureteral reflux (VUR). METHODS: We conducted a retrospective review of patients from 4 Mid-Atlantic institutions between 2015 and 2020. Inclusion criteria included patients with a duplex kidney with upper pole pathology and/or lower pole VUR. The primary outcome was predictive factors for surgical intervention and UTI. The secondary outcome was to assess the natural history of lower pole VUR including resolution rates by grade. Linear regression identified clinical predictors for UTI events. Multivariate logistic regression identified predictors of surgical intervention, UTI, and lower pole VUR resolution. Descriptive statistics and regression modeling analyses were performed using SAS. RESULTS: Two hundred forty-two patients were included with a total of 271 duplex renal units. Hydronephrosis grade (both SFU and UTD grading) and number of prior UTI events were statistically significant predictors for surgical intervention (p = 0.03/0.001 and p = 0.002 respectively). Ectopic ureter (p = 0.004), ureterocele (p = 0.02), and obstruction (p = 0.04) were the only pathologies predictive for surgery. Male gender and circumcision were significantly associated with decreased UTI risk (p = 0.03 and p = 0.01). On linear regression modeling, antibiotic prophylaxis after the first year of life was associated with decreased risk of further UTI events (p = 0.03); however, antibiotic prophylaxis within the first year of life did not decrease UTI risk (p = 0.14). For VUR outcomes, 65.0% of grades 1-3 VUR and 52.2% of grades 4-5 had resolution/improvement at mean time of 2.1 years. There were no predictive factors for resolution/improvement of VUR. CONCLUSIONS: Hydronephrosis grade and UTI events were significant predictors for surgical intervention for upper pole pathology. Pathologies that were predictive for surgery included ectopic ureter, ureterocele and obstruction. Male gender, circumcision and antibiotic prophylaxis after the first year of life were associated with a decreased UTI risk. Roughly 58% of lower pole VUR spontaneously improved/resolved. Identification of these risk factors aids in standardization of care practices to reduce long-term UTI risk and inform counseling with families about possible need for surgical intervention and expectations for long term outcomes.

Continuous antibiotic prophylaxis in isolated prenatal hydronephrosis.

BACKGROUND: Prenatal hydronephrosis (PNH) is one of the most common congenital anomalies and can increase the risk of developing a urinary tract infection (UTI) in the first two years of life. Continuous antibiotic prophylaxis (CAP) has been recommended empirically to prevent UTI in children with PNH, but its use has been controversial. OBJECTIVE: We describe the incidence of UTI in children with isolated PNH of the renal pelvis without ureteral dilation. Our objective was to compare patients receiving and not receiving CAP and determine whether CAP is beneficial at preventing UTI in children with isolated PNH. STUDY DESIGN: Children with confirmed PNH were enrolled between 2008 and 2020 into the Society for Fetal Urology Hydronephrosis Registry. Children with isolated dilation of the renal pelvis without ureteral or bladder abnormality were included. The primary outcome was development of a UTI, comparing patients who were prescribed and not prescribed CAP. RESULTS: In this cohort of 801 children, 76% were male, and 35% had high grade hydronephrosis (SFU grades 3-4). CAP was prescribed in 34% of children. The UTI rate among all children with isolated PNH was 4.2%. Independent predictors of UTI were female sex (HR = 13, 95% CI: 3.8-40, p = 0.0001), intact prepuce (HR = 5.1, 95% CI: 1.4-18, p = 0.01) and high grade hydronephrosis (HR = 2.0, 95% CI: 0.99-4.0, p = 0.05; Table) on multivariable analysis. For patients on CAP, the UTI rate was 4.0% compared to 4.3% without CAP (p = 0.76). The risk of UTI during follow-up was not significantly different between patients who received CAP and patients who were not exposed to CAP; adjusting for sex, circumcision status and hydronephrosis grade (HR = 0.72, 95% CI: 0.34-1.5, p = 0.38). In sub-group analysis of patients at higher risk of UTI (uncircumcised males, females and high grade hydronephrosis), CAP use was not associated with a statistically significant reduction in UTI. CONCLUSIONS: The overall UTI rate in children with isolated PNH is very low at 4.2%. In the overall population of patients with isolated PNH, CAP was not associated with reduction in UTI risk, although the limitations in our study make characterizing CAP effectiveness difficult. Clinicians should consider risk factors prior to placing all patients with isolated PNH on CAP.

Risk of urinary tract infection in patients with hydroureter: An analysis from the Society of Fetal Urology Prenatal Hydronephrosis Registry.

BACKGROUND: Prenatal hydronephrosis is one of the most common anomalies detected on prenatal ultrasonography. Patients with prenatal hydronephrosis and ureteral dilation are at increased risk of urinary tract infection (UTI) and continuous antibiotic prophylaxis (CAP) is recommended. However, current guidelines do not define the minimum ureteral diameter that would be considered a dilated ureter in these patients. OBJECTIVE: We evaluate the definition of clinically relevant hydroureter, its association with UTI, and the impact of CAP. STUDY DESIGN: Patients with prenatal hydronephrosis from seven centers were enrolled into the Society for Fetal Urology Prenatal Hydronephrosis Registry from 2008 to 2020. Patients with ureteral measurement on ultrasound were included. Patients with ureterocele, ectopic ureter, neurogenic bladder, posterior urethral valves, horseshoe or solitary kidney, known ureteropelvic junction obstruction, or follow-up less than one month were excluded. Primary outcome was UTI. Analyses were performed using Cox regression. RESULTS: Of the 1406 patients enrolled in the registry, 237 were included. Seventy-six percent were male, ureteral diameter ranged from 1 to 34 mm, and median follow-up was 2.2 years. Patients with ureters 7 mm or greater had nearly three times the risk of UTI adjusting for sex, circumcision status, antibiotic prophylaxis and hydronephrosis grade (HR = 2.7, 95% CI: 1.1-6.5, p = 0.03; Figure). In patients who underwent voiding cystourethrogram (VCUG; 200/237), ureteral dilation of 7 mm or more identified patients at increased UTI risk controlling for sex, circumcision status, vesicoureteral reflux and hydronephrosis grade (HR = 2.3, 95% CI: 0.97-5.6, p = 0.06). CAP was significantly protective against UTI (HR = 0.50 (95% CI: 0.28-0.87), p = 0.01). Among patients who underwent VCUG and did not have vesicoureteral reflux, ureteral dilation 7 mm or greater corresponded with higher UTI risk compared to ureteral diameter less than 7 mm on multivariable analysis (HR = 4.6, 95% CI: 1.1-19.5, p = 0.04). CONCLUSIONS: This is the first prospectively collected, multicenter study to demonstrate that hydroureter 7 mm or greater identifies a high-risk group for UTI who benefit from antibiotic prophylaxis. In contrast, patients with prenatal hydronephrosis and non-refluxing hydroureter less than 7 mm may be managed more conservatively.

Varenicline limits ischemia reperfusion injury following testicular torsion in mice.

BACKGROUND: Torsion of the spermatic cord and the resulting testicular ischemia leads to the production of inflammatory cytokines and cell death due to impaired aerobic metabolism. Following reperfusion of the testis, a robust innate inflammatory response furthers tissue injury due to the production of reactive oxygen species and disruption of normal capillary function. Blunting the innate immune response with antioxidants, anti-inflammatory medications and targeted genetic interventions reduces long term testicular injury in animal models of torsion, however these approaches have limited clinical applicability. Mediated via α7 nACh receptors, the cholinergic anti-inflammatory pathway limits NFKB signaling and prevents renal fibrosis following warm renal ischemia. We identified varenicline as an FDA approved α7 nAChR agonist and hypothesized that varenicline administration would decrease long-term testicular atrophy and fibrosis in a murine model of testicular torsion. METHODS: Using an established model, unilateral testicular torsion was induced in mature male CD1 mice by rotating the right testicle 720° for 2 h. In the treatment group, 4 doses of varenicline (1mg/grm) were administered via intraperitoneal injection every 12 h, with the first dose given 1 h after the creation of testicular torsion. The acute inflammatory response was evaluated 48 h following reperfusion of the testis. Long term outcomes were evaluated 30 days following testicular perfusion. RESULTS: 48 h following reperfusion, the testis of animals treated with varenicline demonstrated a significant reduction in the inflammatory response as measured by the acute immune cell infiltrate, myeloperoxidase activity, concentration of reduced glutathione and expression of downstream NF-KB targets. 30 days following reperfusion, animals treated with varenicline, demonstrated decreased testicular atrophy (Summary Figure), fibrosis and expression of pro-fibrotic genes. CONCLUSION: Activation of a central immunosuppressive cascade with varenicline after the onset of testicular torsion reduces ischemia reperfusion injury and prevents long term testicular atrophy and fibrosis. Further studies are needed to define the optimum dose and varenicline administration regimen. Our results suggest that varenicline offers a novel, FDA approved, adjunct to the current management of testicular torsion.

Design and development of the Pediatric Urology Recovery After Surgery Endeavor (PURSUE) multicentre pilot and exploratory study.

INTRODUCTION: Lower urinary tract reconstruction in paediatric urology represents a physiologically stressful event that is associated with high complication rates, including readmissions and emergency room visits. Enhanced recovery after surgery (ERAS) protocol is a set of multidisciplinary, perioperative strategies designed to expedite surgical recovery without adversely impacting readmission or reoperation rates. Early paediatric urology data demonstrated ERAS reduced complications in this population. METHODS AND ANALYSIS: In 2016, a working group of paediatric urologists and anaesthesiologists convened to develop an ERAS protocol suitable for patients undergoing lower urinary tract reconstruction and define study process measures, patient-reported outcomes and clinically relevant outcomes in paediatric and adolescent/young adult patients. A multicentre, prospective, propensity-matched, case-control study design was chosen. Each centre will enrol five pilot patients to verify implementation. Subsequent enrolled patients will be propensity matched to historical controls. Eligible patients must be aged 4-25 years and undergoing planned operations (bladder augmentation, continent ileovesicostomy or appendicovesicostomy, or urinary diversion). 64 ERAS patients and 128 controls will be needed to detect a decrease in mean length of stay by 2 days. Pilot phase outcomes include attainment of ≥70% mean protocol adherence per patient and reasons for protocol deviations. Exploratory phase primary outcome is ERAS protocol adherence, with secondary outcomes including length of stay, readmissions, reoperations, emergency room visits, 90-day complications, pain scores, opioid usage and differences in Quality of Recovery 9 scores. ETHICS AND DISSEMINATION: This study has been registered with authors' respective institution review boards and will be published in peer-reviewed journals. It will provide robust insight into the feasibility of ERAS in paediatric urology, determine patient outcomes and allow for iteration of ERAS implementations as new best practices and evidence for paediatric surgical care arise. We anticipate this study will take 4 years to fully accrue with completed follow-up. TRIAL REGISTRATION NUMBER: NCT03245242; Pre-results.

High incidence of abnormal imaging findings in circumcised boys diagnosed with urinary tract infections.

BACKGROUND: The American Academy of Pediatrics guidelines recommend delaying voiding cystourethrogram (VCUG) until the second febrile urinary tract infection (UTI). Similarly, the NICE Guidelines do not recommend VCUG after the first febrile UTI in infants and children under three years of age. Currently, there is no good clinical indicator to determine which patients would benefit from an earlier cystogram. Here, we sought to identify clinical and bacteriologic findings that are associated with an increased risk of urinary tract anatomic anomalies in pediatric males presenting to the Emergency Department with a UTI. METHODS: A retrospective review was performed of all urine cultures from the Emergency Department at our institution between 2006 and 2015. Males under 18 years of age with ≥50,000 CFU/mL of Proteus, Klebsiella, Escherichia coli, Staphylococcus, Streptococcus and Enterococcus were included. Clean catch, catheterized and suprapubic aspiration specimens were included. Bagged specimens and specimens from patients on intermittent catheterization were excluded. Ultrasound and cystogram images were reviewed when available. Univariate and multivariable Poisson regression with robust variance was used to calculate and compare prevalence ratios. Statistical analysis was performed with Stata software, version 15.1 MP (Stata Corporation, College Station, Texas, USA). RESULTS: We reviewed 1585 urine cultures, of which 812 met eligibility criteria including 619 (76.2%) E. coli, 84 (10.3%) Proteus, 55 (6.8%) Klebsiella, 29 (3.6%) Staphylococcus, 13 (1.6%) Enterococcus and 12 (1.5%) Streptococcus. Median age was six months (2.4-36 months IQR). After adjusting for age, ethnicity and bacterial species, the prevalence of dilating vesicoureteral reflux (VUR, defined as grades III-V) was 5.3 times higher in circumcised males compared to uncircumcised males (95% CI: 2.4-11.4, p = 0.001). Circumcised males had a 3.1 times increased prevalence of high-grade hydronephrosis (defined as SFU grades 3 and 4) compared to uncircumcised males (prevalence ratio: 3.1, 95% CI: 1.0-10.0, p = 0.05). Among bacterial pathogens, no patients with Proteus UTI had high-grade hydronephrosis or dilating VUR. In contrast, Staphylococcal infections were associated significantly with dilating VUR (prevalence ratio 10.1, 95% CI: 2.3, 44.8; p = 0.002) and high-grade hydronephrosis (prevalence ratio 8.1, 95% CI: 1.7, 39.7; p = 0.010). CONCLUSIONS: Circumcision status is an independent predictor of structural urinary anomalies of the bladder and upper tracts in pediatric males with UTI, therefore circumcised males should be considered for early imaging, including VCUG, after their first UTI. Furthermore, Staphylococcal infections were associated with an even higher prevalence of high-grade hydronephrosis and dilating VUR and therefore warrant early investigation with VCUG. In contrast, none of the Proteus infections, which were seen almost exclusively in uncircumcised males, were associated with dilating VUR or hydronephrosis, making initial observation more appropriate in these patients.

IPSE, a parasite-derived host immunomodulatory protein, is a potential therapeutic for hemorrhagic cystitis.

Chemotherapy-induced hemorrhagic cystitis is characterized by bladder pain and voiding dysfunction caused by hemorrhage and inflammation. Novel therapeutic options to treat hemorrhagic cystitis are needed. We previously reported that systemic administration of the Schistosomiasis hematobium-derived protein H-IPSEH06 (IL-4-inducing principle from Schistosoma mansoni eggs) is superior to three doses of MESNA in alleviating hemorrhagic cystitis (Mbanefo EC, Le L, Pennington LF, Odegaard JI, Jardetzky TS, Alouffi A, Falcone FH, Hsieh MH. FASEB J 32: 4408-4419, 2018). Based on prior reports by others on S. mansoni IPSE (M-IPSE) and additional work by our group, we reasoned that H-IPSE mediates its effects on hemorrhagic cystitis by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation, and translocating to the nucleus to modulate expression of genes implicated in relieving bladder dysfunction. We speculated that local bladder injection of the S. hematobium IPSE ortholog IPSEH03, hereafter called H-IPSEH03, might be more efficacious in preventing hemorrhagic cystitis compared with systemic administration of IPSEH06. We report that H-IPSEH03, like M-IPSE and H-IPSEH06, activates IgE-bearing basophils in a nuclear factor of activated T-cells reporter assay, indicating activation of the cytokine pathway. Furthermore, H-IPSEH03 attenuates ifosfamide-induced increases in bladder wet weight in an IL-4-dependent fashion. H-IPSEH03 relieves hemorrhagic cystitis-associated allodynia and modulates voiding patterns in mice. Finally, H-IPSEH03 drives increased urothelial cell proliferation, suggesting that IPSE induces bladder repair mechanisms. Taken together, H-IPSEH03 may be a potential novel therapeutic to treat hemorrhagic cystitis by basophil activation, attenuation of allodynia, and promotion of urothelial cell proliferation.

Robotic-assisted laparoscopic MACE.

INTRODUCTION: The creation of a Malone antegrade continence enema (MACE) channel is an option to treat patients with neurologic conditions that result in fecal soiling or intractable constipation. It is typically performed in an open fashion through a midline incision or laparoscopically. The laparoscopic technique typically involves bringing the tip of the appendix to the skin whereas the open technique allows for imbrication of the cecum around the channel, which may improve continence and decrease the risk of perforation. Herein, we demonstrate a technique to create a MACE using both robotic-assisted and laparoscopic techniques that allows for imbrication of the channel without requiring an open incision. MATERIALS AND METHODS: Three robotic ports are placed in the midline and a fourth port is placed in the right lower quadrant at the location of the MACE stoma. Two mesenteric fenestrations are made along the appendix in order to imbricate the cecum around the channel. The tip of the appendix is then brought to through the laparoscopic port in the right lower quadrant, and matured to the skin. DISCUSSION: The MACE procedure can safely be performed using a robotic-assisted technique that allows for imbrication of the cecum around the channel and improved cosmesis.

A practice pattern assessment of members of the Society of Pediatric Urology for evaluation and treatment of urinary tract dilation.

INTRODUCTION: Over the last decade the literature, including a multidisciplinary consensus statement, has supported a paradigm shift in management of urinary tract dilation, yet the impact on practice patterns has not been well documented. OBJECTIVE: This study aims to elucidate specific practice patterns for treatment of prenatal unilateral urinary tract dilation and to assess surgical intervention patterns for ureteropelvic junction obstruction. STUDY DESIGN: An online survey was distributed to 234 pediatric urologists through the Society of Pediatric Urology. The survey was composed of five clinical case scenarios addressing evaluation and management of unilateral urinary tract dilation. RESULTS: The response rate was 71% (n = 168). Circumcision status, gender, and grade were significant factors in recommending prophylactic antibiotics for newborn urinary tract dilation. Prophylactic antibiotic use in the uncircumcised male and female was twice that of a circumcised male for grade 3 (Table). This difference was minimized for grade 4. Use of VCUG was high for circumcised males with grade 3 or 4 (Table). The choice of minimally invasive surgery for ureteropelvic junction repair increased with age from 19% for a 5-month-old, 49% for a 2-year-old, and 85% for a 10-year-old. Notably, 44% of respondents would observe a 10-year-old with intermittent obstruction. Retrograde pyelography was recommended in conjunction with repair in 65% of respondents. Antegrade stent placement was the most common choice (38-47%) for urinary diversion after pyeloplasty. Regarding postoperative imaging, only 5% opted for routine renal scan whereas most would perform renal ultrasound alone. DISCUSSION: Practice patterns seen for use of prophylactic antibiotics are in agreement with the literature, which promotes selective use in those at highest risk for urinary tract infections. Interestingly, use of aggressive screening was not concordant with this literature. Several studies have indicated an increased usage of robotic pyeloplasty; however, results indicate that minimally invasive surgery is not preferred in those younger than 6 months. Study limitations include use of clinical case scenarios as opposed to actual clinical practice. CONCLUSION: Practice patterns for prophylactic antibiotic use for neonatal urinary tract dilation are dependent on gender, circumcision status, and grade. The use of minimally invasive surgery for ureteropelvic junction repair increased with patient age, with 50% preferring this modality at 2 years.

Urinary tract infections in children with prenatal hydronephrosis: A risk assessment from the Society for Fetal Urology Hydronephrosis Registry.

INTRODUCTION: Risk factors for urinary tract infection (UTI) in children with prenatal hydronephrosis (PNH) are not clearly defined. Our study aim was to describe incidence and identify factors associated with UTI among a cohort of children diagnosed with PNH. MATERIAL AND METHODS: Patients with confirmed PNH from four medical centers were prospectively enrolled in the Society for Fetal Urology (SFU) hydronephrosis registry between 9/2008 and 10/2015. Exclusion criteria included enrollment because of UTI, associated congenital anomalies, and less than 1-month follow-up. Univariate analysis was performed using Fisher's Exact test or Mann-Whitney U. Probability for UTI was determined by Kaplan-Meier curve. RESULTS: Median follow-up was 12 (IQR 4-20) months in 213 patients prenatally diagnosed with hydronephrosis. The majority of the cohort was male (72%), Caucasian (77%), and 26% had high grade (SFU 3 or 4) hydronephrosis. Circumcision was performed in 116/147 (79%) with known status, 19% had vesicoureteral reflux (VUR), and 11% had ureteral dilatation. UTI developed in 8% (n = 18), 89% during their first year of life. Univariate analysis found UTI developed more frequently in females (p < 0.001), uncircumcised males (p < 0.01), and the presence of parenchymal renal cyst (p < 0.05). Logistic regression found renal cyst to no longer be significant, but female gender a significant risk factor for development of UTI (p < 0.001). Regression analysis stratified by gender found neither hydronephrosis grade nor parenchymal renal cyst to be significant risk factors for UTI development among females. However, hydronephrosis grade and circumcision status were significant risk factors for development of UTI among males (p < 0.05 and p < 0.01, respectively). CONCLUSION: Identification of factors associated with UTI in patients with PNH is still progressing; however, several observational studies have identified groups that may be at increased risk of UTI. Use of prophylactic antibiotics (PA), degree of kidney dilation, gender, and circumcision status all have been reported to have some degree of impact on UTI. A previous study identified risk factors for UTI as female gender, uncircumcised status, hydroureteronephrosis, and VUR, and reported that prophylaxis provided a protective effect on prevention of UTI. Our data mirror those in some respect, identifying an association of UTI with female gender and, among males, uncircumcised status, and high grade hydronephrosis. However, we were unable to demonstrate an association between UTI and the use of PA, presence of VUR, dilated ureter, or renal duplication in this observational registry.

Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis.

Here we demonstrate a new paradigm in redox signaling, whereby oxidants resulting from metabolic stress directly alter protein palmitoylation by oxidizing reactive cysteine thiolates. In mice fed a high-fat, high-sucrose diet and in cultured endothelial cells (ECs) treated with high palmitate and high glucose (HPHG), there was decreased HRas palmitoylation on Cys181/184 (61±24% decrease for cardiac tissue and 38±7.0% in ECs). This was due to oxidation of Cys181/184, detected using matrix-assisted laser desorption/ionization time of flight (MALDI TOF)-TOF. Decrease in HRas palmitoylation affected its compartmentalization and Ras binding domain binding activity, with a shift from plasma membrane tethering to Golgi localization. Loss of plasma membrane-bound HRas decreased growth factor-stimulated ERK phosphorylation (84±8.6% decrease) and increased apoptotic signaling (24±6.5-fold increase) after HPHG treatment that was prevented by overexpressing wild-type but not C181/184S HRas. The essential role of HRas in metabolic stress was made evident by the similar effects of expressing an inactive dominant negative N17-HRas or a MEK inhibitor. Furthermore, the relevance of thiol oxidation was demonstrated by overexpressing manganese superoxide dismutase, which improved HRas palmitoylation and ERK phosphorylation, while lessening apoptosis in HPHG treated ECs.

Redox regulation of sirtuin-1 by S-glutathiolation.

Sirtuin-1 (SIRT1) is an NAD(+)-dependent protein deacetylase that is sensitive to oxidative signals. Our purpose was to determine whether SIRT1 activity is sensitive to the low molecular weight nitrosothiol, S-nitrosoglutathione (GSNO), which can transduce oxidative signals into physiological responses. SIRT1 formed mixed disulfides with GSNO-Sepharose, and mass spectrometry identified several cysteines that are modified by GSNO, including Cys-67 which was S-glutathiolated. GSNO had no effect on basal SIRT1 deacetylase activity, but inhibited stimulation of activity by resveratrol (RSV) with an IC(50) of 69 microM. These observations indicate that S-glutathiolation of SIRT1 by low concentrations of reactive glutathione can modulate its enzymatic activity.