Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group.

BACKGROUND: The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy. METHODS: ARST1431 was a randomised, open-label, phase 3 trial conducted across 210 institutions in Australia, Canada, New Zealand, and the USA. Eligible patients were those aged 40 years or younger with non-metastatic FOXO1-positive rhabdomyosarcoma or unresected FOXO1-negative rhabdomyosarcoma disease from unfavourable sites. Two other groups of patients were also eligible: those who had FOXO1-negative disease at a favourable site (excluding orbit) that was unresected; and those who were aged younger than 10 years with stage IV FOXO1-negative disease with distant metastases. Eligible patients had to have a Lansky performance status score of 50 or higher if 16 years or younger and a Karnofsky performance status score of 50 or higher if older than 16 years; all patients were previously untreated. Patients were randomised (1:1) in blocks of four and stratified by histology, stage, and group. Patients received intravenous VAC/VI chemotherapy with a cyclophosphamide dose of 1·2 g/m2 per dose per cycle with or without a reducing dose of intravenous weekly temsirolimus starting at 15 mg/m2 or 0·5 mg/kg per dose for those who weighed less than 10 kg. The total duration of therapy was 42 weeks followed by 6 months of maintenance therapy with oral cyclophosphamide plus intravenous vinorelbine for all patients. Temsirolimus was withheld during radiotherapy and for 2 weeks before any major surgical procedure. The primary endpoint was 3-year event-free survival. Data were analysed with a revised intention-to-treat approach. The study is registered with ClinicalTrials.gov (NCT02567435) and is complete. FINDINGS: Between May 23, 2016, and Jan 1, 2022, 325 patients were enrolled. In 297 evaluable patients (148 assigned to VAC/VI alone and 149 assigned to VAC/VI with temsirolimus), the median age was 6·3 years (IQR 3·0-11·3); 33 (11%) patients were aged 18 years or older; 179 (60%) of 297 were male. 113 (77%) of 148 patients were FOXO1 negative in the VAC/VI group, and 108 (73%) of 149 were FOXO1 negative in the VAC/VI with temsirolimus group. With a median follow-up of 3·6 years (IQR 2·8-4·5), 3-year event-free survival did not differ significantly between the two groups (64·8% [95% CI 55·5-74·1] in the VAC/VI group vs 66·8% [57·5-76·2] in the VAC/VI plus temsirolimus group (hazard ratio 0·86 [95% CI 0·58-1·26]; log-rank p=0·44). The most common grade 3-4 adverse events were anaemia (62 events in 60 [41%] of 148 patients in the VAC/VI group vs 89 events in 87 [58%] of 149 patients in the VAC/VI with temsirolimus group), lymphopenia (83 events in 65 [44%] vs 99 events in 71 [48%]), neutropenia (160 events in 99 [67%] vs 164 events in 105 [70%]), and leukopenia (121 events in 86 [58%] vs 132 events in 93 [62%]). There was one treatment-related death in the VAC/VI with temsirolimus group, categorised as not otherwise specified. INTERPRETATION: Addition of temsirolimus to VAC/VI did not improve event-free survival in patients with intermediate-risk rhabdomyosarcoma defined by their FOXO1 translocation status and clinical factors. Novel biology-based strategies are needed to improve outcomes in this population. FUNDING: The Children's Oncology Group (supported by the US National Cancer Institute, US National Institutes of Health).

Pediatric urothelial cancer: a cross-sectional descriptive analysis of the National Cancer Database.

Background: Urothelial cancer is a rare pediatric malignancy; previous analyses suggest lower rates of recurrence and death as compared to adults. We analyzed pediatric bladder cancer information in a national database, hypothesizing that survival would be better in children than adults. Methods: We analyzed the 2004-2016 National Cancer Database (NCDB) for children and adolescents (0-18 years) with urothelial bladder cancer. Rhabdomyosarcoma patients were excluded. Assessed variables included TNM staging, pathology, tumor size, surgical procedures, and post-operative re-admissions. Overall survival was defined as months since diagnosis as of last follow-up. Results: Of 140 urothelial tumors reported to NCDB between 2004-2016, 75.7% (N=106) were stage 0 at diagnosis, 6.4% (N=9) were stage I, 2.9% (N=4) were stage II and 3.6% (N=5) were stage IV, while 11.4% cases (N=16) were unknown. From available mortality data (121 patients), no patients died after definitive surgical resection. Only 1 mortality was reported at 90 days, although cause of death was reportedly unknown. Three (2.5%) patients were lost to follow-up, and most (96.7%) were alive at 90 days. Conclusions: Short-term survival outcomes among children and adolescents with urothelial bladder tumors captured in NCDB are reassuring. Future investigations focused on long-term outcomes and appropriate surveillance in this rare patient cohort are imperative to better guide management options.

Radiation-induced Sarcoma of the Prostate After Treatment for Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is among the most common pediatric solid malignancies. Fusion-negative, embryonal RMS is the predominant histology among prostate and bladder lesions. Management strategies depend on the clinical stage and risk group. Although the optimal strategy continues to evolve, the field has transitioned from radical upfront resection to organ preservation strategies with multi-modal therapy, including chemotherapy, radiation, and surgery. Survivors frequently develop late complications, including impaired fertility and sexual function, bladder dysfunction, and secondary malignancies. Our case describes an 11-year-old male who developed a radiation-induced prostatic sarcoma. We present a novel surgical technique and highlight the importance of multidisciplinary care.

Comparing binary & ordinal definitions of urinary & stool continence outcomes: Data from the National Spina Bifida Patient Registry.

INTRODUCTION: The National Spina Bifida Patient Registry (NSBPR) assesses bladder and bowel incontinence using ordinal categories, but prior NSBPR analyses employed binary classification. Our aims were to 1) perform the first NSBPR analysis of bladder and bowel incontinence as ordinal outcomes to compare to the binary definition and subject variables; 2) explore the correlation of incontinence with undergarment usage, and 3) assess incontinence status following continence surgeries. METHODS: Data from NSBPR participants' most recent clinic visit from 2013 to 2020 were analyzed. Ordinal categories of incontinence were compared to previously used binary definitions. Incontinence surgical outcomes were analyzed for those with data at least three months post-operatively. Chi-square tests evaluated associations among categorical variables. Univariate and ordinal logistic regression models were used to test associations of ordinal incontinence status with patient and condition factors. Statistical tests were 2-sided; p values < 0.05 were considered significant. RESULTS: Analysis of 7217 individuals using ordinal incontinence outcomes showed little difference from previously used binary outcomes. The final multivariable logistic regression models with ordinal multinomial outcomes showed that associations of incontinence with age, sex, race/ethnicity, health insurance, level of lesion, and continence management technique were similar to prior studies. Among those reporting never being incontinent of both bladder and bowel, 14% reported using protective undergarments. Of the 500 individuals who had bladder outlet surgery, 38% reported never being incontinent of urine. Of 1416 individuals who had appendicostomy (ACE) bowel surgery, 48% reported never being incontinent of stool. DISCUSSION: Our current analysis showed that ordinal continence outcome classification had similar continence findings as previous studies using the binary definition of continence. Expanding the binary definition of continence to include monthly episodes of incontinence did not greatly increase the proportion of continent individuals and, therefore, would have not likely made meaningful differences in continence outcomes in prior NSBPR analyses. However, it is known that even mild incontinence can affect quality of life, therefore, capturing any level of incontiennce is of clinical importance. Confirmation of the association of continence outcomes with sociodemographic, condition-related, and interventional factors with both approaches further validates previous analyses using the binary definition of continence. CONCLUSION: The previously used binary definition of bladder and bowel continence appears robust. Undergarment choice was a poor surrogate for reported incontinence. After bladder and bowel continence surgeries, 38% and 48%, respectively, reported never being incontinent.

Causes of death among people with myelomeningocele: A multi-institutional 47-year retrospective study.

PURPOSE: This study aimed to analyze organ system-based causes and non-organ system-based mechanisms of death (COD, MOD) in people with myelomeningocele (MMC), comparing urological to other COD. METHODS: A retrospective review was performed of 16 institutions in Canada/United States of non-random convenience sample of people with MMC (born > = 1972) using non-parametric statistics. RESULTS: Of 293 deaths (89% shunted hydrocephalus), 12% occurred in infancy, 35% in childhood, and 53% in adulthood (documented COD: 74%). For 261 shunted individuals, leading COD were neurological (21%) and pulmonary (17%), and leading MOD were infections (34%, including shunt infections: 4%) and non-infectious shunt malfunctions (14%). For 32 unshunted individuals, leading COD were pulmonary (34%) and cardiovascular (13%), and leading MOD were infections (38%) and non-infectious pulmonary (16%). COD and MOD varied by shunt status and age (p < = 0.04), not ambulation or birthyear (p > = 0.16). Urology-related deaths (urosepsis, renal failure, hematuria, bladder perforation/cancer: 10%) were more likely in females (p = 0.01), independent of age, shunt, or ambulatory status (p > = 0.40). COD/MOD were independent of bladder augmentation (p = >0.11). Unexplained deaths while asleep (4%) were independent of age, shunt status, and epilepsy (p >= 0.47). CONCLUSION: COD varied by shunt status. Leading MOD were infectious. Urology-related deaths (10%) were independent of shunt status; 26% of COD were unknown. Life-long multidisciplinary care and accurate mortality documentation are needed.

Critical elements of pediatric rhabdomyosarcoma surgery.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, requires multimodal therapy which is determined by risk group stratification. Local control may be achieved by surgical resection, radiation, or both. Resection may occur upfront or following induction chemotherapy as a delayed primary excision. An R1 resection may allow a reduction in radiation exposure; however, debulking is not indicated nor is excision of residual masses at the end of therapy. Regional lymph node assessment is an important component of surgical care, as positive nodal basins require radiation. Depending on the tumor site and biology, sentinel lymph node biopsy vs biopsy of clinically or radiographically concerning nodes is indicated. Therapeutic lymph node dissection is never indicated. Familiarity with site-specific oncologic principles for RMS and participation in a multidisciplinary team including Pediatric Oncology and Radiation Oncology are necessary components of surgical care to ensure optimal outcomes.

Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of "persistency" in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex.

The Persistency Index: a novel screening tool for identifying myofascial pelvic floor dysfunction in patients seeking care for lower urinary tract symptoms.

BACKGROUND: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome. Despite a high influence on quality of life, low awareness of this condition combined with no objective diagnostic testing leads to the frequent misdiagnosis or underdiagnosis of myofascial urinary frequency syndrome. OBJECTIVE: This study aimed to develop a screening measure to identify patients with myofascial urinary frequency syndrome (bothersome lower urinary tract symptoms secondary to myofascial pelvic floor dysfunction) from patient-reported symptoms. STUDY DESIGN: A population of patients with isolated myofascial urinary frequency syndrome was identified by provider diagnosis from a tertiary urology practice and verified by standardized pelvic floor myofascial examination and perineal surface pelvic floor electromyography. Least Angle Shrinkage and Selection Operator was used to identify candidate features from the Overactive Bladder Questionnaire, Female Genitourinary Pain Index, and Pelvic Floor Distress Index predictive of myofascial urinary frequency syndrome in a pooled population also containing subjects with overactive bladder (n=42), interstitial cystitis/bladder pain syndrome (n=51), and asymptomatic controls (n=54) (derivation cohort). A simple, summated score of the most discriminatory questions using the original scaling of the Pelvic Floor Distress Index 5 (0-4) and Genitourinary Pain Index 5 (0-5) and modified scaling of Female Genitourinary Pain Index 2b (0-3) had an area under the curve of 0.75. As myofascial urinary frequency syndrome was more prevalent in younger subjects, the inclusion of an age penalty (3 points added if under the age of 50 years) improved the area under the curve to 0.8. This score was defined as the Persistency Index (possible score of 0-15). The Youden Index was used to identify the optimal cut point Persistency Index score for maximizing sensitivity and specificity. RESULTS: Using a development cohort of 215 subjects, the severity (Pelvic Floor Distress Index 5) and persistent nature (Female Genitourinary Pain Index 5) of the sensation of incomplete bladder emptying and dyspareunia (Female Genitourinary Pain Index 2b) were the most discriminatory characteristics of the myofascial urinary frequency syndrome group, which were combined with age to create the Persistency Index. The Persistency Index performed well in a validation cohort of 719 patients with various lower urinary tract symptoms, including overactive bladder (n=285), interstitial cystitis/bladder pain syndrome (n=53), myofascial urinary frequency syndrome (n=111), controls (n=209), and unknown diagnoses (n=61), exhibiting an area under the curve of 0.74. A Persistency Index score ≥7 accurately identified patients with myofascial urinary frequency syndrome from an unselected population of individuals with lower urinary tract symptoms with 80% sensitivity and 61% specificity. A combination of the Persistency Index with the previously defined Bladder Pain Composite Index and Urge Incontinence Composite Index separated a population of women seeking care for lower urinary tract symptoms into groups consistent with overactive bladder, interstitial cystitis/bladder pain syndrome, and myofascial urinary frequency syndrome phenotypes with an overall diagnostic accuracy of 82%. CONCLUSION: Our study recommends a novel screening method for patients presenting with lower urinary tract symptoms to identify patients with myofascial urinary frequency syndrome. As telemedicine becomes more common, this index provides a way of screening for myofascial urinary frequency syndrome and initiating pelvic floor physical therapy even before a confirmatory pelvic examination.

Recurrent Papillary Bladder Tumors in a Boy With Lynch Syndrome.

Lynch syndrome (LS) is an autosomal dominant genetic disorder defined by germline mutations in one of four mismatch repair genes including PMS2, MLH2, MSH1, MSH2, or deletion in the EPCAM gene.1 The most common urologic manifestation of LS is upper tract urothelial carcinoma, which occurs in up to 20% of patients with LS.2 While data are scarce, there is growing evidence of an increased relative risk of bladder malignancy in patients with LS.3,4 Bladder tumors in children are a rare entity and the link between pediatric bladder tumors and LS has not been previously reported to our knowledge.

Myofascial Frequency Syndrome: A novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

Background: Patients presenting with lower urinary tract symptoms (LUTS) are historically classified to several symptom clusters, primarily overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Accurate diagnosis, however, is challenging due to overlapping symptomatic features, and many patients do not readily fit into these categories. To enhance diagnostic accuracy, we previously described an algorithm differentiating OAB from IC/BPS. Herein, we sought to validate the utility of this algorithm for identifying and classifying a real-world population of individuals presenting with OAB and IC/BPS and characterize patient subgroups outside the traditional LUTS diagnostic paradigm. Methods: An Exploratory cohort of 551 consecutive female subjects with LUTS evaluated in 2017 were administered 5 validated genitourinary symptom questionnaires. Application of the LUTS diagnostic algorithm classified subjects into controls, IC/BPS, and OAB, with identification of a novel group of highly bothered subjects lacking pain or incontinence. Symptomatic features of this group were characterized by statistically significant differences from the OAB, IC/BPS and control groups on questionnaires, comprehensive review of discriminate pelvic exam, and thematic analysis of patient histories. In a Reassessment cohort of 215 subjects with known etiologies of their symptoms (OAB, IC/BPS, asymptomatic microscopic hematuria, or myofascial dysfunction confirmed with electromyography), significant associations with myofascial dysfunction were identified in a multivariable regression model. Pre-referral and specialist diagnoses for subjects with myofascial dysfunction were catalogued. Findings: Application of a diagnostic algorithm to an unselected group of 551subjects presenting for urologic care identified OAB and IC/BPS in 137 and 96 subjects, respectively. An additional 110 patients (20%) with bothersome urinary symptoms lacked either bladder pain or urgency characteristic of IC/BPS and OAB, respectively. In addition to urinary frequency, this population exhibited a distinctive symptom constellation suggestive of myofascial dysfunction characterized as "persistency": bothersome urinary frequency resulting from bladder discomfort/pelvic pressure conveying a sensation of bladder fullness and a desire to urinate. On examination, 97% of persistency patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. We therefore classified this symptom complex "myofascial frequency syndrome". To confirm this symptom pattern was attributable to the pelvic floor, we confirmed the presence of "persistency" in 68 patients established to have pelvic floor myofascial dysfunction through comprehensive evaluation corroborated by symptom improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming that myofascial frequency syndrome is a distinct LUTS symptom complex. Interpretation: This study describes a novel, distinct phenotype of LUTS we classified as myofascial frequency syndrome in approximately one-third of individuals with urinary frequency. Common symptomatic features encompass elements in other urinary syndromes, such as bladder discomfort, urinary frequency and urge, pelvic pressure, and a sensation of incomplete emptying, causing significant diagnostic confusion for providers. Inadequate recognition of myofascial frequency syndrome may partially explain suboptimal overall treatment outcomes for women with LUTS. Recognition of the distinct symptom features of MFS (persistency) should prompt referral to pelvic floor physical therapy. To improve our understanding and management of this as-yet understudied condition, future studies will need to develop consensus diagnostic criteria and objective tools to assess pelvic floor muscle fitness, ultimately leading to corresponding diagnostic codes. Funding: This work was supported by the AUGS/Duke UrogynCREST Program (R25HD094667 (NICHD)) and by NIDDK K08 DK118176 and Department of Defense PRMRP PR200027, and NIA R03 AG067993.

Single-port hidden incision endoscopic (HIdES) pediatric nephrectomy via pfannenstiel incision.

Laparoendoscopic single-site surgery (LESS) and hidden incision endoscopic surgery techniques are increasingly used in pediatric urology. For pediatric nephrectomy, access through a single Pfannenstiel incision is novel and may offer cosmetic benefit. In this retrospective study, we describe this approach and assess operative outcomes associated with this technique. Patients who underwent LESS nephrectomy through a single Pfannenstiel incision had minimal blood loss, short length of stay, low risk of surgical complications, and satisfactory wound healing. The Pfannenstiel approach to LESS nephrectomy is feasible, versatile, and achieves excellent operative and cosmetic outcomes, although direct comparison to other approaches is warranted.

Red CdSe/ZnS QDs' Intracellular Trafficking and Its Impact on Yeast Polarization and Actin Filament.

Quantum dots are nanoparticles (2-10 nm) that emit strong and tunable fluorescence. Quantum dots have been heavily used in high-demand commercialized products, research, and for medical purposes. Emerging concerns have demonstrated the negative impact of quantum dots on living cells; however, the intracellular trafficking of QDs in yeast cells and the effect of this interaction remains unclear. The primary goal of our research is to investigate the trafficking path of red cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) in Saccharomyces cerevisiae and the impact QDs have on yeast cellular dynamics. Using cells with GFP-tagged reference organelle markers and confocal microscopy, we were able to track the internalization of QDs. We found that QDs initially aggregate at the exterior of yeast cells, enter the cell using clathrin-receptor-mediated endocytosis, and distribute at the late Golgi/trans-Golgi network. We also found that the treatment of red CdSe/ZnS QDs resulted in growth rate reduction and loss of polarized growth in yeast cells. Our RNA sequence analysis revealed many altered genes. Particularly, we found an upregulation of DID2, which has previously been associated with cell cycle arrest when overexpressed, and a downregulation of APS2, a gene that codes for a subunit of AP2 protein important for the recruitment of proteins to clathrin-mediated endocytosis vesicle. Furthermore, CdSe/ZnS QDs treatment resulted in a slightly delayed endocytosis and altered the actin dynamics in yeast cells. We found that QDs caused an increased level of F-actin and a significant reduction in profilin protein expression. In addition, there was a significant elevation in the amount of coronin protein expressed, while the level of cofilin was unchanged. Altogether, this suggests that QDs favor the assembly of actin filaments. Overall, this study provides a novel toxicity mechanism of red CdSe/ZnS QDs on yeast actin dynamics and cellular processes, including endocytosis.

Medical management of neurogenic bladder in patients with spina bifida: A scoping review.

INTRODUCTION: Neurogenic bladder is a common source of morbidity in patients with spina bifida and can cause renal damage. Medical management may include imaging, urodynamic studies (UDS), laboratory testing, clean intermittent catheterization (CIC), and medication. There is ongoing debate regarding the optimal management regimen. Approaches are described by two paradigms: proactive and expectant management. In a proactive approach, invasive interventions like CIC and UDS are initiated before the onset of renal abnormalities. In expectant management, UDS, CIC, and medications are started after abnormalities are identified. In this scoping review, we aim to comprehensively review existing literature on outcomes of proactive and expectant management of neurogenic bladder in patients with spina bifida. METHODS: We searched multiple databases and screened articles for inclusion using PRISMA-ScR guidelines. Included studies reported clinical outcomes of any aspect of proactive or expectant neurogenic bladder management in patients with spina bifida. RESULTS: Ultimately, 74 articles were included for review including 67 cohort studies, 4 cross-sectional studies, 2 sequential cohort studies, and 1 randomized control trial. Eleven studies directly compared management strategies. There was substantial heterogeneity in study designs, management protocols, and reported outcomes. Most studies addressed multiple simultaneous aspects of management without specifically analyzing individual aspects. However, some commented on individual aspects of management including UDS (13), CIC (32), imaging (7), and medication (5). Although there was no consensus about optimal management, all direct comparisons of paradigms supported a proactive approach. CONCLUSION: Our review identified a broad body of literature about optimal management of neurogenic bladder. Existing studies vary greatly in terms of treatment protocols, measured outcomes, and management recommendations. Overall, studies that directly compare management are scarce but favor proactive management. Given the implications on clinical outcomes, it is crucial to focus future work on directly comparing management strategies and isolating the effects of different individual management elements.

Robot-assisted laparoscopic anterior urethral diverticulectomy.

INTRODUCTION AND HYPOTHESIS: A 31-year-old patient with a history of fetal sacrococcygeal teratoma requiring tumor resection and pelvic reconstruction in infancy presented with a 3-year history of recurrent vulvar abscesses and voiding dysfunction. Magnetic resonance imaging demonstrated a fluid collection posterior to the pubic bone and inferior to the bladder. The objective was to demonstrate the key steps in the resection and repair of an anterior urethral diverticulum via robot-assisted laparoscopic approach. METHODS: Cystoscopy followed by robot-assisted laparoscopic retropubic dissection was used for resection of an anterior urethral diverticulum followed by urethral reconstruction. RESULTS: Cystoscopy revealed a large anterior cavity at the midpoint of the urethra consistent with an anterior urethral diverticulum. This likely tracked inferiorly toward her vulva during repeated episodes of infection expressing through her recurrent abscesses. Retropubic space exploration revealed dense fibrotic tissue adherent to the underside of the pubic tubercule contiguous with the anterior urethral diverticulum, which was successfully resected. CONCLUSIONS: Female anterior urethral diverticulum is a rare entity. A robot-assisted laparoscopic approach can be safely utilized to identify and resect an anterior urethral diverticulum. Key points include optimization of port placement, use of a council-tip catheter to facilitate bladder drainage in the setting of distorted pelvic anatomy, and multi-layered tension-free urethral closure with flap placement.

Framing the picture: Impact of radiographic imaging on parental vesicoureteral reflux management preferences.

INTRODUCTION/OBJECTIVE: Given the variety of treatment options for vesicoureteral reflux (VUR), shared decision making between clinicians and parents is essential. Despite its importance, shared decision making is limited by the framing effect - people process the same information differently depending on how it is presented. Studies have also demonstrated that showing patients their radiology images can impact behaviors. In this pilot study, we sought to determine if showing parents radiographic images could serve as a framing tool that impacts the decision of whether to pursue surgery, endoscopic intervention, or conservative management for VUR. METHODS: We designed a survey instrument which provided background on VUR and a hypothetical scenario of a 2-year-old child with VUR who had a breakthrough febrile urinary tract infection (UTI). Guideline-concordant management options were presented: (1) change antibiotics, (2) endoscopic management, or (3) open or laparoscopic surgery. All options were similarly presented regarding risks, benefits, and length of stay. Respondents were randomized into a group with no image accompanying the clinical scenario or a group which had a labeled image of a voiding cystourethrogram (VCUG) demonstrating unilateral VUR. Respondents also answered demographic and health experience questions. The instrument was published on Amazon's Mechanical Turk online work interface which provides reliable and validated results in VUR experiments. Parents aged 18-60 years old were eligible. Responses with failed attention questions, duplicate internet addresses, or submission times <1 or >30 min were disqualified. Data were analyzed using t-test, chi-square, and multinomial logistic regression. Sensitivity analyses were performed after excluding all responses submitted under 2, 3, and 5 min. RESULTS: There were a total of 914 responses, 426 met inclusion criteria. The presence or absence of a VCUG image did not result in a statically significant difference in the management decision (p = 0.081). Multinomial logistic regression demonstrated that prior UTI experience influenced the management decision (p = 0.027). Sensitivity analyses revealed a significant difference in the management decision when excluding responses <5 min (p = 0.039). CONCLUSION: In this analysis, there was no statistically significant framing effect by radiographic images on parental management decision for VUR. Multinomial analyses suggested that prior experience with UTI has an impact on VUR management decisions. These results need to be considered within the limitations of this pilot study - the respondents were given a hypothetical clinical scenario and the survey instrument cannot replace an in-office discussion. Further analyses on framing and its role in pre-operative counseling is warranted.

Variation in care between pediatric and adult patients presenting with nephrolithiasis to tertiary care pediatric emergency departments in the United States (2009-2020).

BACKGROUND: Individuals with nephrolithiasis frequently present to the Emergency Department (ED). Safety and quality principles are often applied in pediatric EDs to children presenting with nephrolithiasis, such as limiting ionizing radiation exposure and opioid analgesics. However, it is unknown whether pediatric EDs apply these same principles to adult patients who present with nephrolithiasis. We hypothesized that adult patients would be associated with higher use of radiation-based imaging and opioid analgesics. OBJECTIVE: To assess variations in diagnostic and treatment interventions and hospital utilization between pediatric and adult patients presenting to the pediatric ED with nephrolithiasis. STUDY DESIGN: A retrospective cohort study was conducted, examining outcomes for pediatric (<18-years-old) versus adult (≥18-years-old) patients in 42 pediatric EDs from 2009 to 2020 using the Pediatric Health Information System (PHIS) database. Patients with an ICD-9/10 principal diagnosis code of nephrolithiasis with no nephrolithiasis-related visits within the prior 6 months were included. Primary outcomes were imaging, medications, and surgical interventions. Secondary outcomes were hospital admissions, 90-day ED revisits, and 90-day readmissions. Generalized linear mixed models with random effects were used to adjust for confounding and clustering. RESULTS: In total, 16,117 patients with 17,837 encounters were included. Most hospitals were academic (95.2%), and a plurality were located in the South (38.1%). Most patients were <18-years-old (84.4%, median (interquartile range): 15 (12-17)-years-old), female (57.9%), and White (76.3%), and 17.1% were Hispanic/Latino. Most had no complex chronic conditions (89.2%) and no chronic disease per pediatric medical complexity algorithm (51.5%). For the primary outcome, adults, relative to pediatric patients, who presented to the pediatric ED with nephrolithiasis had higher adjusted odds of receiving computerized tomography (CT) scans (Odds Ratio [OR] 1.43 [95% Confidence Interval [CI] 1.29-1.59]) and opioid analgesics (OR 1.45 [95%CI 1.33-1.58]) (Summary Figure). Secondary outcomes showed that adults, relative to pediatric patients, had lower adjusted odds of hospital admissions, 90-day ED revisits, and 90-day readmissions. DISCUSSION: Our results suggest that certain pediatric safety and quality principles, such as limiting ionizing radiation exposure and opioid analgesic prescriptions, are not being equally applied to pediatric and adult patients who present to pediatric EDs with nephrolithiasis. The mechanism of these findings remains to be elucidated. CONCLUSIONS: Variations in care for individuals with nephrolithiasis reflect an opportunity for quality improvement in pediatric EDs and inform work exploring optimal care pathways for all patients presenting to the pediatric ED with nephrolithiasis.