Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

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.

Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

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.

Women Are Underrepresented in Prestigious Recognition Awards in the American Urological Association.

OBJECTIVE: To determine the proportion of women who received awards from the American Urological Association (AUA) and evaluate whether this has changed over time as the proportion of practicing female urologists has increased. METHODS: A retrospective review of award recipients from the AUA website was performed. Gender of award recipient, type of award and year received were collected and the trend over time was compared with the AUA census. RESULTS: Of the 622 award recipients, 43 (6.9%) were women. There was a larger proportion of women who received early career awards (15/65; 23.1%) compared to women who received more prestigious mid (1/44; 2.3%) or senior (27/513; 5.3%) career awards. Additionally, 17/43 (39.5%) of female award recipients were not clinical urologists, compared to only 33/579 (5.7%) of male award recipients. CONCLUSION: Despite increased representation by women in the field of urology, women remain underrepresented in awards given by the AUA. Although the proportion of women receiving awards over time has increased, it remains less than expected given the increased proportion of practicing female urologists. Strategic initiatives should be employed to help advance women in academic urology.

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.

Hidden consequences of patient satisfaction: A survey of pediatric surgeons.

BACKGROUND: Patient satisfaction surveys are increasingly utilized to assess patients' perceptions of their health care. Recently, these scores have been linked to payment, potentially incentivizing practices to meet certain metrics. We hypothesize that increasing pressures to receive positive reviews have led physicians to alter the delivery of their care to accommodate patient expectations over standards of care. METHODS: An 11-question REDCap™ survey was developed and emailed anonymously to all sixty-two surgeons across all surgical subspecialties at our children's hospital. Multiple-choice and open-ended questions were included. A modified Delphi method was used to acquire general consensus. RESULTS: Survey response rate for analysis was 41/62 (66%). 23 (56%) stated that they have changed their clinical practice patterns due to concerns regarding patient dissatisfaction. Examples of such changes included: requesting imaging tests or laboratory studies, performing invasive procedures, referring for second opinions, and prescribing medications. Only 2% felt that these interventions led to any significant change in outcome of a patient's condition. Several respondents expressed concerns that factors outside their control (scheduling, parking, wait times) contributed to patient dissatisfaction and affected providers' ratings, while others expressed concerns about inherent biases driving survey participants. CONCLUSIONS: As a result of patient satisfaction surveys, a significant number of surgeons reported altering their clinical practice beyond standard care to meet patient expectations. Some of these modifications included performing unnecessary interventions. Reliance on these surveys may be at odds with reducing health care costs and avoiding physician burnout. These and other unintended consequences of patient satisfaction surveys warrant further study before they are widely accepted as appropriate quality metrics. LEVEL OF EVIDENCE: Level IV, questionnaire.

Association of spina bifida with cancer.

While the worldwide incidence of newborns with spinal dysraphism is decreasing, the majority of children now survive and reach adulthood, creating new challenges in patient management and long-term care. Despite medical and surgical advances with a subsequent decline in mortality, spina bifida continues to be a major cause of chronic disability and affected individuals face increased mortality in adulthood. The majority of spina bifida patients have neurogenic bladder. Reconstructive and diverting procedures may increase the neoplastic risk in the urinary tract over time, however bladder dysfunction itself may be a risk factor, therefore patients, caregivers, and physicians must be aware of the baseline risk of cancer in patients with neurogenic bladder, in addition to routine cancer screening. Optimal treatment of myelomeningocele requires a multidisciplinary care team to prevent and manage potential sequelae that may affect function, quality of life, and survival.

A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress.

INTRODUCTION: The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity. METHODS: A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. RESULTS: There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (≤90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100%. CONCLUSION: This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions.

Interrater Reliability in Interpretation of Neuropathic Pediatric Urodynamic Tracings: An Expanded Multicenter Study.

PURPOSE: Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study. MATERIALS AND METHODS: We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement. RESULTS: The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively). CONCLUSIONS: Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes.

Modulation of the rat micturition reflex with transcutaneous ultrasound.

INTRODUCTION: Low intensity focused ultrasound has recently been identified as a novel method of stimulating targeted neurons. We hypothesized that ultrasound stimulation of the posterior tibial nerve would inhibit bladder contractions in an established rat model of rhythmic bladder contractions. METHODS: Cyclical detrusor contractions were initiated by placing a transurethral catheter in female rats and infusing saline into the bladder. Transcutaneous ultrasound pulses were then delivered to the lower extremity of a rat (overlying the posterior tibial nerve) using a single element spherically focused 250 kHz transducer. Sixty-three cycles were repeated at 2 kHz for 300 ms at peak negative pressure of 900 kPa pulsed at 0.5 Hz. RESULTS: We report successful suppression of bladder contractions using ultrasound stimulation in 10 animals. The average latency between the initiation of ultrasound and suppression of bladder contractions was 3 min 23 s (±51 s), the average time of contraction suppression was 13 min and 50 s (±2 min 25 s) and the average time from the end of ultrasound to return of contractions was 9 min 37 s (±2 min and 30 s). CONCLUSION: In this work, we demonstrate the ability of targeted transcutaneous ultrasound to inhibit rhythmic bladder contractions in anesthetized rats. Due to its non-invasive nature and ease of application, we believe ultrasound mediated suppression of the micturition reflex is potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

Interrater Reliability in Pediatric Urodynamic Tracings: A Pilot Study.

PURPOSE: Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice. MATERIALS AND METHODS: We retrospectively identified patients with neuropathic bladder who underwent urodynamics at our institution between 2014 and 2015. An anonymous electronic survey (phase I) was developed with 20 clinical scenarios, each containing a brief history, a single urodynamic tracing and an accompanying fluoroscopic image. Faculty members assessed each tracing by an online instrument developed using urodynamic reports and published literature. The primary outcome was statistical correlation across raters as measured by the Spearman correlation coefficient. In a followup study (phase II) we investigated the sources of variability in urodynamic interpretations. RESULTS: Six faculty members completed the study with a response rate of 100%. In comparing urodynamic interpretation across raters, the faculty demonstrated a weak to strong correlation (rs 0.39-0.61, p <0.001). A strong correlation was found for fluoroscopic and clinical decision making variables, while electromyography synergy and detrusor overactivity demonstrated weaker correlation across physicians. CONCLUSIONS: Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care.

Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli.

The ability to de novo synthesize purines has been associated with the intracellular survival of multiple bacterial pathogens. Uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections, undergoes a transient intracellular lifestyle during which bacteria clonally expand into multicellular bacterial communities within the cytoplasm of bladder epithelial cells. Here, we characterized the contribution of the conserved de novo purine biosynthesis-associated locus cvpA-purF to UPEC pathogenesis. Deletion of cvpA-purF, or of purF alone, abolished de novo purine biosynthesis but did not impact bacterial adherence properties in vitro or in the bladder lumen. However, upon internalization by bladder epithelial cells, UPEC deficient in de novo purine biosynthesis was unable to expand into intracytoplasmic bacterial communities over time, unless it was extrachromosomally complemented. These findings indicate that UPEC is deprived of purine nucleotides within the intracellular niche and relies on de novo purine synthesis to meet this metabolic requirement.