Real-world treatment drop-off among recurrent or metastatic cervical cancer patients: A US community oncology-based analysis.

OBJECTIVE: Understanding real-world treatment patterns and proportions of eligible patients in each line of treatment is imperative to inform future clinical trial designs and multi-line treatment algorithm development. METHODS: We conducted a retrospective observational cohort study of adult women who received first-line (1 L) therapy for r/mCC between 01 September 2014 and 31 December 2019, using The US Oncology Network electronic health records and chart review data. Patients were followed to 31 December 2020. Patient demographic and clinical characteristics, treatment patterns, and clinical outcomes were assessed descriptively. RESULTS: A total of 262 patients with r/mCC met study inclusion criteria (mean age = 53 years). The majority of patients in 1 L received platinum-based chemotherapy doublet plus bevacizumab (66%) or chemotherapy doublet alone (24%). Nearly half the patients (48%) completing 1 L received 2 L therapy. Among these patients, there was no consistent 2 L treatment of choice. Overall median time to treatment discontinuation was 3.5 months from 1 L treatment initiation, and median overall treatment-free interval was 2.1 months from 1 L discontinuation. Besides elevated serum creatinine, abnormal BMI indicated a directional trend for lower likelihood of receiving 2 L. Other predictors may include no prior bevacizumab, worse ECOG, and earlier disease prevention. CONCLUSIONS: >50% of the patients who initiated 1 L treatment did not receive 2 L therapy, highlighting the need for novel and effective treatment options. As the treatment landscape continues to evolve, we anticipate that more patients will live longer with more treatment options across multiple lines of therapies in the r/mCC setting.

Voiding cystourethrogram: Who gets a cyclic study and does it matter?

BACKGROUND: Voiding cystourethrogram (VCUG) images the urethra and bladder during both bladder filling and emptying, as well as the ureters and kidneys when vesicoureteral reflux (VUR) is present. Given the variation in VCUG technique and reporting, the American Academy of Pediatrics Sections on Urology and Radiology published a joint standardized VCUG protocol in 2016, which included the recommendation of at least 2 voiding cycles to identify intermittent VUR and/or ureteral ectopia. STUDY DESIGN: VCUG were assessed for adherence to performance of cyclic study. Children who underwent cyclic evaluation were compared to those who underwent a single cycle VCUG. Radiation dosage was also analyzed. Studies performed on patients >18 years of age and those obtained as part of a trauma evaluation were excluded from study. RESULTS: Two hundred and eighty-four VCUGs were analyzed, 97 (34.2%) were positive for VUR on the initial cycle. Of the remaining 187 studies, 116 (62%) had multiple filling-voiding cycles while in 71 (38%) only a single cycle was performed. One hundred and sixty-one (86.1%) were negative for vesicoureteral reflux. Twenty-six (13.9%) children were diagnosed with VUR after the initial filling-voiding cycle: 6 were diagnosed with grade I, 2 grade II, 11 grade III, 2 grade IV and 5 grade V. Of the 123 total children found to have VUR, 26 (21.2%) were diagnosed after an initial negative cycle. Younger children were significantly more likely to have a cyclic study performed; mean age of patients undergoing a cyclic study was 1.09 ± 2.16 years versus 3.86 ± 4.5 years (p ≤ 0.0001). Categorically, 74.1% of children less than 1 year of age underwent a cyclic study compared to 6.9% of children older than 5 years of age (p ≤ 0.0001). There was no difference based on sex with 49.1% of males and 50.9% of females (p = 0.667) undergoing cyclic evaluation. Children undergoing a cyclic study had lower median radiation dose 2.15 microGy m2 (range 0.09-111) compared to 4.41 (range 1.3-104) [p = 0.01]. DISCUSSION: Vesicoureteral reflux may occur intermittently and cyclic VCUG is thought to enhance the ability to detect reflux. In our cohort, 26 children (9.2%) were only diagnosed after an additional cycle - ie 21.1% of reflux would have been missed had a cyclic study not been performed. The majority of these patients (69.2%, 18 of 26) were found to have dilating, and thus perhaps more clinically significant, reflux. Our study highlights the importance of obtaining as much information as possible and adhering to the standardized VCUG protocol. CONCLUSION: Younger children are more likely to undergo cyclic VCUG. While most reflux is detected with the initial filling-voiding cycle, 26 (21.2%) patients were diagnosed after an initial negative cycle with the majority being dilating VUR.

Order Set Use and Education Association With Pediatric Acute Pancreatitis Outcomes.

BACKGROUND: The management of acute pancreatitis (AP) in children was historically derived from adult practice recommendations. Pediatric-specific recommendations for treatment of AP were recently developed by North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, but their impact on clinical outcomes has yet to be evaluated. We developed an AP order set on the basis of these recommendations to assess impact on clinical outcomes. METHODS: Patients admitted to a single center with 3 children's hospitals in 2017 and 2018 for isolated AP were included in a retrospective review. Patient demographic data, order set use, treatment variables (eg, fluid type, rate, type and timing of diet initiation, and narcotic use), and outcome variables (eg, length of stay [LOS], PICU admission, and 30-day readmission) were collected. Mixed-effects modeling was used to estimate the impact of order set use on clinical outcomes. RESULTS: There were 159 pancreatitis encounters and 137 unique patients who met inclusion criteria. In 2018, when using the log transform of LOS in a linear mixed-effects model for clustering by hospital, there was a 10% decrease in mean LOS, but this failed to reach statistical significance (P = .30). Among the 107 encounters who received at least 1 dose of narcotic, there were significantly fewer doses prescribed after implementation of the order set: mean (SD) of5.22 (2.86) vs 3.59 (2.47) (P < .001). Thirty-day readmission (P = .25) and PICU admission rates (P = .31) were not different between years. CONCLUSIONS: The implementation of a pancreatitis order set is associated with a significant decrease in narcotic use in pediatric patients with AP without increasing readmission rates or PICU admissions.

Standardized protocol for voiding cystourethrogram: Are recommendations being followed?

BACKGROUND: Voiding cystourethrogram (VCUG) images the urethra and bladder during filling and emptying, as well as ureters and kidneys when vesicoureteral reflux (VUR) is present, providing detailed information about both anatomical and functional status of the urinary tract. Given the importance of information obtained, and the varying quality depending on VCUG technique and radiology reporting, the American Academy of Pediatrics Sections on Urology and Radiology published a joint standardized VCUG protocol in 2016. OBJECTIVE: We compared VCUG reports from multiple institutions before and after publication of the protocol to determine adherence to recommendations. STUDY DESIGN: VCUG reports generated during two separate time periods were assessed - before and after publication - to evaluate impact of the protocol. Adherence to the reporting template was evaluated. Studies performed on patients >18 years of age and those obtained for trauma evaluation were excluded from study. RESULTS: A total of 3121 VCUG reports were analyzed, 989 (31.7%) were generated before and 2132 (68.3%) after protocol publication. Comparing cohorts, there was no difference in gender (62.6% female versus 61.4%; p = 0.53) though children in the post-cohort were slightly older (3.34 ± 3.82 versus 3.68 ± 4.19 years; p = 0.03). A significant increase in scout image reporting (91.5%) and cyclic studies (20.5%) were observed in the post-cohort, in comparison to 79.2% and 13.1%, respectively, in the pre-protocol cohort (p < 0.001) [Figure]. Measured PVR and recorded infused volume actually decreased between study periods (84.7% vs 72.8% and 97.2% vs 91.5%, p < 0.001). There was no statistically significant difference between VUR grade reporting (99.4 vs 98.5%, p = 0.25). Recorded volume in which reflux occurred increased between periods (0.6% vs 2.3%, p < 0.05), while reporting of filling vs voiding reflux decreased in the post-cohort (84.4% pre-vs 77.4% post-protocol, p < 0.008). DISCUSSION: The 2016 VCUG protocol recommended inclusion of various data points, however the volume at which reflux occurs remained vastly underreported. Timing of reflux has been shown to predict likelihood of spontaneous resolution and risk of breakthrough urinary tract infection; thus, its omission may limit the information used to counsel families and provide individualized care. CONCLUSION: Despite consensus on standard VCUG protocol to best perform and record data, reports remain inconsistent. While VUR grade is routinely reported, other important anatomic and functional findings which are known to impact resolution and breakthrough urinary tract infection rates, such as volume at which reflux occurs, are consistently underreported.

Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio.

PURPOSE: The vesicoureteral reflux index is a simple, validated tool for predicting resolution of reflux. Along with likelihood of spontaneous resolution identification of children at risk for febrile urinary tract infection impacts management. We evaluated the usefulness of the vesicoureteral reflux index as a predictive factor for breakthrough febrile urinary tract infection compared to reflux grade and distal ureteral diameter ratio. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram data were identified. A 1 to 6-point index was assigned, and ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 to L3 vertebral bodies. Random forest modeling and logistic multivariable regression were employed to estimate the predictive ability of grade, ureteral diameter ratio and vesicoureteral reflux index with regard to breakthrough febrile urinary tract infection. RESULTS: We analyzed 94 girls and 45 boys with a mean±SD age of 5.4±4.7 months at diagnosis. Mean±SD length of followup was 32.1±24.5 months. A total of 13 children (9.4%) experienced breakthrough febrile urinary tract infection. On univariate analysis ureteral diameter ratio (p=0.01) and vesicoureteral reflux index (p=0.0005) were associated with breakthrough urinary tract infection, while grade (p=0.09) did not reach significance. Area under the curve was generated as a measure of accuracy for each variable and was 0.77 for the vesicoureteral reflux index, 0.71 for ureteral diameter ratio and 0.68 for grade, indicating superiority of the vesicoureteral reflux index for predicting breakthrough febrile urinary tract infection. CONCLUSIONS: Children with higher vesicoureteral reflux index are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. The vesicoureteral reflux index provides valuable prognostic information about infection risk, facilitating improved clinical decision making.

Effects of Second-Hand Smoke on Pancreatitis in Children.

OBJECTIVES: Pediatric pancreatitis incidence is increasing, but little is known about risk factors. Smoking increases the risk for adult pancreatitis and has been shown to affect CFTR function in vitro. Therefore, we evaluated passive smoke exposure effects on disease outcomes in children with various pancreatitis etiologies. METHODS: We conducted a 5-year retrospective chart review of patients admitted for pancreatitis to Children's Healthcare of Atlanta. Demographic data, etiology of pancreatitis, and number of hospitalizations with length of stay (LOS) were compared with smoking exposure, obtained through telephone query. RESULTS: Of the 134 subjects admitted for pancreatitis, 90 reported no smoke exposure (none), 33 reported outdoor smoke exposure (outside), and 11 reported exposure to indoor smoking (inside). Average hospital admissions (P = 0.038) and LOS (P = 0.004) were significantly higher among subjects with inside smoke exposure compared with those with outdoor or no exposure. Average hospital admissions were significantly higher in subjects with CFTR mutations compared with those with nongenetic or other genetic etiologies (P ≤ 0.001). CONCLUSIONS: Second-hand smoke exposure may increase hospital admission rates and LOS for pediatric pancreatitis. Children with an identifiable CFTR mutation may have increased risk for hospital admissions compared with those who do not.

Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary Tract Infection.

PURPOSE: Distal ureteral diameter ratio is an objective measure that is prognostic of spontaneous resolution of vesicoureteral reflux. Along with likelihood of resolution, improved identification of children at risk for recurrent febrile urinary tract infections may impact management decisions. We evaluated the usefulness of ureteral diameter ratio as a predictive factor for breakthrough febrile urinary tract infections. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram were identified. Ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 and L3 vertebral bodies. Demographics, vesicoureteral reflux grade, laterality, presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were tested in univariate and multivariable analyses. Primary outcome was breakthrough febrile urinary tract infections. RESULTS: We analyzed 112 girls and 28 boys with a mean ± SD age of 2.5 ± 2.3 years at diagnosis. Vesicoureteral reflux was grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%) and grade 5 in 10 (7.2%). Mean ± SD followup was 3.2 ± 2.7 years. A total of 40 children (28.6%) experienced breakthrough febrile urinary tract infections. Ureteral diameter ratio was significantly greater in children with (0.36) vs without (0.25) breakthrough febrile infections (p = 0.004). Controlling for vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to 2.26, p <0.0001). CONCLUSIONS: Children with increased distal ureteral diameter ratio are at greater risk for breakthrough febrile urinary tract infections independent of reflux grade. Ureteral diameter ratio provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making.

Hospital-acquired Urinary Tract Infections in Neonatal ICU Patients: Is Voiding Cystourethrogram Necessary?

OBJECTIVE: To evaluate the radiographic findings of neonatal intensive care unit (NICU) patients diagnosed with hospital-acquired urinary tract infection (UTI). MATERIALS AND METHODS: Children with no preexisting genitourinary anomalies undergoing a voiding cystourethrogram (VCUG) for culture-documented UTI during NICU admission were identified. Demographics, microbiology results, and imaging findings were evaluated. RESULTS: A total of 147 NICU patients underwent VCUG during the study period. Of these, the indication for VCUG was UTI in 58 children. Neonates diagnosed with UTI were born at a mean gestational age of 28 3/7 ± 4 3/7 weeks, and underwent VCUG at a mean of age of 70.3 ± 42 days. Urine culture grew Enterococcus in 32 (55.2%), Enterobacter in 6 (10.3%), coagulase negative staphylococcus in 6 (10.3%), Escherichia coli in 5 (8.7%), and other in 9 infants (15.5%). All patients underwent a retroperitoneal ultrasound, which was read as normal in 31 patients (53.4%). Fourteen children (24.1%) diagnosed with UTI were found to have vesicoureteral reflux on VCUG. On univariate analysis, no patient characteristics were associated with VCUG positivity. On multivariate analysis, the effect of age at VCUG differed by renal-bladder ultrasound results. Patients with an abnormal ultrasound were 3.6 (95% confidence interval, 1.39-9.24) times more likely to have a positive VCUG for every 1 month increase in age. CONCLUSION: Ultrasound anomalies are common in NICU patients diagnosed with UTI. The effect of age at VCUG differed by ultrasound result; the probability of vesicoureteral reflux in infants with sonographic abnormalities and UTI increases with age.

Validation of the ureteral diameter ratio for predicting early spontaneous resolution of primary vesicoureteral reflux.

INTRODUCTION AND OBJECTIVE: Management of primary vesicoureteral reflux (VUR) remains controversial, and reflux grade currently constitutes an important prognostic factor. Previous reports have demonstrated that distal ureteral diameter ratio (UDR) may be more predictive of outcome than vesicoureteral reflux (VUR) grade. We performed an external validation study in young children, evaluating early spontaneous resolution rates relative to reflux grade and UDR. STUDY DESIGN: Voiding cystourethrograms (VCUGs) were reviewed. UDR was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between the L1 and L3 vertebral bodies (Figure). VUR grade and UDR were tested in univariate and multivariable analyses. Primary outcome was status of VUR at last clinical follow-up (i.e. resolution, persistence, or surgical intervention). Demographics, VUR timing, laterality, and imaging indication were also assessed. RESULTS: One-hundred and forty-seven children (98 girls, 49 boys) were diagnosed with primary VUR at a mean age of 5.5 ± 4.7 months. Sixty-seven (45.6%) resolved spontaneously, 55 (37.4%) had persistent disease, and 25 (17%) were surgically corrected. Patients who spontaneously resolved had significantly lower VUR grade, refluxed later during bladder filling, and had significantly lower UDR. In a multivariable model, grade of VUR (p = 0.001), age <12 months (p = 0.008), ureteral diameter (p = 0.02), and UDR (p < 0.0001) achieved statistical significance. For every 0.1 unit increase in UDR, there was a 2.6 (95% CI 1.58-4.44) increased odds of persistent VUR, whereas a 1.6 (95% CI 0.9-3.0) increased odds was observed for every unit increase in grade. DISCUSSION: Both grade of reflux and UDR were statistically significant in a multivariable model; however, UDR had a higher likelihood ratio and was more predictive of early spontaneous resolution than grade alone. Furthermore, unlike traditional VUR grading where children with grade 1-5 may outgrow reflux depending on other factors, there appears to be a consistent UDR cutoff whereby patients are unlikely to resolve. In the present study, no child with a UDR greater than 0.43 experienced early spontaneous resolution, and only three (4.5%) of those with spontaneous resolution had a UDR above 0.35. CONCLUSIONS: UDR correlates with reflux grade, and is predictive of early resolution in children with primary VUR. UDR is an objective measurement of VUR, and provides valuable prognostic information about spontaneous resolution, facilitating more individualized patient care.

Delayed upper tract drainage on voiding cystourethrogram may not be associated with increased risk of urinary tract infection in children with vesicoureteral reflux.

INTRODUCTION: Urinary stasis in the setting of obstruction provides an opportunistic environment for bacterial multiplication and is a well-established risk factor for UTI. Vesicoureteral reflux (VUR) with delayed upper tract drainage (UTD) on VCUG has been reported to correlate with increased UTI risk. We sought to determine whether delayed UTD can be reliably classified, and whether it correlates with UTI incidence, VCUG, or endoscopic findings. METHODS: Children undergoing endoscopic surgery for primary VUR (2009-2012) were identified. VUR grade, timing, and laterality were abstracted. Demographics, hydrodistention (HD) grade, reported febrile and culture-proven UTI were assessed. UTD on VCUG was graded on post-void images as 1 = partial/complete UTD or 2 = no/increased UTD. Inter-observer agreement was calculated. Patients were excluded for incomplete imaging or inability to void during VCUG. RESULTS: The cohort included 128 patients (10M, 118F), mean age 4.1 ± 2.1 years. Mean age at diagnosis was 2.8 ± 2.8 years. Mean maximum VUR grade was 3 ± 0.9: 1 (7.8%), 2 (20.3%), 3 (43%), 4 (25.8%), 5 (3.1%). UTD occurred in 45 (35%), and no drainage in 83 (65%) patients. Agreement coefficient between graders was 0.596 (p < 0.0001). Cultures were available in 100 patients (70 positive). Patients experienced a mean of 2 ± 1.2 parent-reported fUTIs and 1.2 ± 1.2 culture-proven UTIs from birth to surgery. UTI rate did not differ by UTD status for parent or culture-proven UTI (Table). On multivariate analysis, no patient characteristic was a significant predictor of UTI based on drainage status. Children diagnosed with VUR before 1 year of age had a higher verified UTI rate (p < 0.001). However, drainage was not a significant predictor of UTI rate and when testing the interaction of drainage and age. CONCLUSION: We sought to determine whether UTD was an accurate predictor of UTI risk to maximize available prognostic information from a single VCUG. Delayed UTD was not a predictor of infection in our patients, nor was it associated with previously described UTI risk factors, such as VUR timing or grade, and voiding dysfunction. Limitations included the retrospective nature of the study in patients undergoing endoscopic VUR treatment, and possible inaccurate UTI reports from parents and pediatricians. UTD can be reliably scored using a binary system with high inter-observer correlation. Our data call into question the previous finding that children with poor UTD are at increased risk of recurrent UTI. Delayed UTD is also not associated with higher HD, or VUR grade compared with those with more prompt UTD.

Effectiveness of red blood cell exchange, partial manual exchange, and simple transfusion concurrently with iron chelation therapy in reducing iron overload in chronically transfused sickle cell anemia patients.

BACKGROUND: Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%. STUDY DESIGN AND METHODS: Medical records of SCA patients on CTT and deferasirox (≥25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group. RESULTS: Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (-17 to +45), +38 (+24 to +105), and -91 (-141 to -48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (-1.6 to +4.3), +2.3 (-6.5 to +8.9), and -5.7 (-10.7 to -0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups. CONCLUSION: We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%.

Vesicoureteral Reflux Index: 2-Institution Analysis and Validation.

PURPOSE: The vesicoureteral reflux index is a novel tool designed to predict spontaneous reflux resolution in infants younger than 2 years. We performed a multi-institutional validation study to confirm the discriminatory power of the vesicoureteral reflux index to predict the vesicoureteral reflux resolution rate in young children. MATERIALS AND METHODS: We identified patients diagnosed with primary vesicoureteral reflux before age 24 months who had 2 or more voiding cystourethrograms available. Demographics, vesicoureteral reflux grade and timing, ureteral anomalies and radiographic outcomes were evaluated. The C-index was estimated for time to event model assessment. RESULTS: A total of 219 girls and 150 boys met study inclusion criteria. Mean ± SD age at diagnosis was 4.7 ± 4.9 months. Of the patients 101 (27.4%) had early to mid filling, 214 (58%) had late filling and 54 (14.6%) had voiding only vesicoureteral reflux. High grade reflux was present in 87 patients (23.6%) and ureteral anomalies were observed in 50 (13.6%). A vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater showed an improvement/resolution rate of 88.2%, 77.3%, 62.3%, 32.1% and 14.3%, respectively. On time to event analysis children with filling phase vesicoureteral reflux (p <0.001), grade 4-5 reflux (p <0.001) and ureteral anomalies (p = 0.003) had significantly longer median time to resolution. Median time to spontaneous resolution was 12.6, 12.7, 15.1, 25.6 and 31 months or greater for a vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater, respectively (C-index 0.305, 95% CI 0.252-0.357). During the study period 65 patients (17.6%) underwent surgical intervention. CONCLUSIONS: The vesicoureteral reflux index is a simple tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in patients diagnosed at younger than 2 years. The index provides valuable prognostic information, facilitating individualized patient care.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Emergency Hospital Admissions for Initial Febrile Urinary Tract Infection: Do Patient Demographics Matter?

BACKGROUND: In 2011, the American Academy of Pediatrics revised practice parameters regarding febrile urinary tract infection (fUTI) in children aged 2-24 months. The Section on Urology opposed the omission of voiding cystourethrogram (VCUG), and expressed concern that potential untoward consequences of deferring VCUG may be most felt by children on Medicaid. OBJECTIVE: We ascertained imaging and characteristics of children presenting to the Emergency Department (ED) with initial fUTI to determine the impact of patient demographics on admissions for pyelonephritis. METHODS: Children aged 2-24 months presenting to the ED with initial fUTI were identified. Demographics, insurance status, laboratory studies, renal-bladder ultrasound (RBUS), VCUG, and hospital admission status were evaluated. RESULTS: Three-hundred fifty patients met inclusion criteria; 88 (25.1%) were admitted. Admitted patients were significantly (p < 0.001) younger (mean 0.31 ± 0.33 years) than those managed as outpatients (mean 0.91 ± 0.7 years). On univariate analysis, male gender (p < 0.001), Medicaid insurance (p < 0.05), and non-Hispanic race (p < 0.05) were associated with admission. Race retained significance on multivariate analysis; Caucasian children were 2.35 times (95% confidence interval [CI] 0.79-7.23) and African-American children 3.8 times more likely to be admitted than Hispanic patients (95% CI 1.88-7.63). Children with abnormal RBUS were 12.8 times more likely to require admission (95% CI 4.44-37.0). Medicaid was also independently predictive of admission; such patients were 2.6 times more likely to be admitted than those with private insurance (95% CI 1.15-5.88). CONCLUSIONS: Abnormal ultrasound, non-Hispanic race, and public insurance were strongly associated with hospital admission in children presenting to the ED with initial febrile urinary tract infection.

Does augmentation cystoplasty with continent reconstruction at a young age increase the risk of complications or secondary surgeries?

INTRODUCTION AND OBJECTIVE: Lower urinary tract reconstruction with augmentation cystoplasty (AC) is an effective strategy for achieving urinary continence in children with neurogenic or severely compromised bladder. We compared complications and need for secondary surgeries in children 3-5 years of age undergoing AC with continent reconstruction to those ≥ 6 years old. STUDY DESIGN: Medical charts of children undergoing AC with continent urinary diversion between 2003 and 2011 were reviewed. Complications and secondary surgeries were analyzed according to patient age. Patient demographics, etiology of bladder dysfunction, bowel segment used, and concomitant procedures were also assessed. RESULTS: One hundred and eight children underwent AC with continent urinary diversion. Mean age at augmentation was 8.5 years (range 3-20). Twenty-eight children (25.9%) were 3-5 years old and 80 (74.1%) were ≥ 6 years. Mean follow-up was 6.93 years (range 1.6-10 years). Bowel segment used included ileum in 59 (54.6%), sigmoid in 33 (30.6%), cecum in 4 (3.7%) and composite in 12 (11.1%). Major complications included bowel obstruction in 6 (5.6%), bladder perforation in 3 (2.8%) and fistula in 2 (1.9%). There was no difference in major complications based on bowel segment utilized (p = 0.804, OR 0.894) or age (p = 0.946, OR 0.969). Fifty children (46.3%) required no additional surgeries; the remaining 58 underwent 137 procedures post-augmentation. Surgeries included urolithiasis management (58/137, 42.3%), appendicovesicostomy revision including stoma revision or redo for persistent leakage between catheterizations in (34/137, 24.8%), bladder neck procedures (26/137, 19%) and revision of MACE (19/137, 13.9%) [Figure]. Incidence of stones in patients 3-5 years (32.1%) was not significantly different than children ≥ 6 years of age (25%, p = 0.463, OR 0.704). Mean number of secondary surgeries for those 3-5 years was 1.21 ± 1.34, which was not statistically different than those ≥ 6 (1.3 ± 1.82, p = 0.154). Children with myelomeningocele (MMC) were statistically more likely to require secondary surgeries than those with other bladder pathology (p = 0.01). DISCUSSION: Augmentation enterocystoplasty with cutaneous continent catheterizable channel is performed both to protect the upper urinary tract and afford the patient the option of social continence. Continent lower urinary tract reconstruction has been proven technically feasible and safe in preschool-aged children however, the ideal age for augmentation remains unknown. Urolithiasis accounted for over 40% of additional procedures in our series, with 26.9% of patients requiring one or more surgeries for stone disease. The incidence of stone disease in patients 3-5 years of age at the time of augmentation was comparable to that seen in older children. The overall need for additional post-augment procedures was not influenced by patient age or bowel segment utilized, however children with MMC were significantly more likely to require future surgeries than those with a different underlying etiology of bladder dysfunction. Our study has several limitations that warrant mention. Children with neurogenic bladder represent a heterogeneous population, and their surgical outcomes are inherently influenced by underlying disease processes and severity. Complications and secondary surgeries were assessed; however success rates were not evaluated in the current study. Patient and caregiver adherence with CIC and daily bladder irrigation was not assessed; whether noncompliance affected complication rates (i.e. stone formation) is unknown. CONCLUSION: Whether performed at a young or older age, families must be adequately counseled regarding the daily management responsibilities and potential risks associated with lower urinary tract reconstruction including bladder augmentation. Augmentation with continent urinary diversion in selected patients 3-5 years of age confers complication and secondary surgery risk equal to that observed in their older counterparts.

Is routine voiding cystourethrogram necessary following double hit for primary vesicoureteral reflux?

INTRODUCTION AND OBJECTIVE: Current AUA guidelines recommend voiding cystourethrogram (VCUG) following endoscopic treatment of vesicoureteral reflux (VUR). We evaluated the clinical and radiographic outcomes of children undergoing Double HIT (hydrodistention implantation technique) for primary VUR to determine success rates and the necessity of postoperative VCUG. STUDY DESIGN: Children with a history of febrile urinary tract infection (fUTI) undergoing Double HIT for primary VUR between 2009 and 2012 were identified. Patients were prospectively classified as high or low clinical and radiographic risk. Children were categorized as high clinical risk if they had ≥ 3 fUTIs or documented bladder bowel dysfunction (BBD). High radiographic risk included those <2 years of age or with grade 4-5 VUR. Initially, all children underwent postoperative VCUG ("routine" group), while only those with an indication (high radiographic risk or clinical failure) did so during the latter portion of the study ("indicated" group). Clinical success was defined as no postoperative fUTI and radiographic success as negative postoperative VCUG. Average clinical follow-up was 34.7 ± 17.2 months. RESULTS: Two hundred and twenty-two children (198 girls, 24 boys) underwent Double HIT at a mean age of 4.1 ± 2.7 years. Mean maximum VUR grade was 3 ± 0.8. Sixty-eight children (30.6%) had documented BBD. Fourteen children (6.3%) experienced postoperative fUTI, for a clinical success rate of 93.7%. One hundred and fourteen patients (51.4%) underwent postoperative VCUG; 76 were "routine" and 38 were "indicated" [Figure]. Of children classified as low clinical/radiographic risk, 96.6% did not have a postoperative fUTI, compared to 91.1% for high risk patients (P = 0.771). Odds of clinical success for routine VCUG group were 9.9 times higher than for the indicated VCUG group (95% CI, 2-50). Odds of radiographic success for the routine cohort were 13 times higher than for the indicated group (95% CI, 4.2-40). Nine children (4.1%) underwent additional procedures. DISCUSSION: We found no difference in clinical success among the different risk groups; the number of children with postoperative fUTI was relatively few so there was not statistical power to discern any differences between patients who experienced clinical success versus clinical failure. However, children with an "indicated" VCUG (i.e. those less than 2 years of age, grade 4-5 VUR or those with a fUTI) were 13 times more likely to experience a radiographic failure. This cohort of 38 patients had a 50% radiographic cure rate and a 78.9% clinical cure rate, compared to the overall long-term clinical success rate of 93.7%. Our data demonstrates that we can predict failures with relatively high sensitivity, and it may therefore be prudent to selectively obtain postoperative VCUG rather than recommend it for all children undergoing dextranomer hyaluronic acid co-polymer (Dx/HA) injection. Our study has several limitations that warrant consideration. Not all children underwent a postoperative VCUG, so the true radiographic success rate is unknown. Incidence of fUTI may also be artificially low, as some radiographic failures proceeded directly to another injection or reimplantation. While we were able to demonstrate that children undergoing an "indicated" VCUG were more likely to experience radiographic failure, a larger patient cohort is necessary to determine whether age or VUR grade is more predictive of failure. Finally all patients underwent endoscopic Dx/HA injection, therefore the incidence "spontaneous resolution" is unknown. CONCLUSION: Long-term clinical success following Double HIT for the endoscopic correction of primary VUR is high, and the majority of children avoid additional procedures. Unless indicated by high-grade, young age, clinical failure, or family/surgeon preference, consideration should be given to making postoperative VCUG an option rather than a recommendation in children undergoing endoscopic treatment of primary VUR using the Double HIT method.

Further analysis of the Glans-Urethral Meatus-Shaft (GMS) hypospadias score: correlation with postoperative complications.

INTRODUCTION AND OBJECTIVE: The Glans-Urethral Meatus-Shaft (GMS) score is a concise and reproducible way to describe hypospadias severity. We classified boys undergoing primary hypospadias repair to determine the correlation between GMS score and postoperative complications. STUDY DESIGN: Between February 2011 and August 2013, patients undergoing primary hypospadias repair were prospectively scored using the GMS classification. GMS scoring included a 1-4 scale for each component: G - glans size/urethral plate quality, M - meatal location, and S - degree of shaft curvature, with more unfavorable characteristics assigned higher scores [Figure]. Demographics, repair type, and complications (urethrocutaneous fistula, meatal stenosis, glans dehiscence, phimosis, recurrent chordee and stricture) were assessed. Total and individual component scores were tested in uni- and multivariate analysis. RESULTS: Two-hundred and sixty-two boys (mean age 12.3 ± 13.7 months) undergoing primary hypospadias repair had a GMS score assigned. Mean GMS score was 7 ± 2.5 (G 2.1 ± 0.9, M 2.4 ± 1, S 2.4 ± 1). Mean clinical follow-up was 17.7 ± 9.3 months. Thirty-seven children (14.1%) had 45 complications. A significant relationship between the total GMS score and presence of any complication (p < 0.001) was observed; for every unit increase in GMS score the odds of any postoperative complication increased 1.44 times (95% CI, 1.24-1.68). Urethrocutaneuous fistula was the most common complication, occurring in 21 of 239 (8.8%) of single-stage repairs. Patients with mild hypospadias (GMS 3-6) had a 2.4% fistula rate vs. 11.1% for moderate (GMS 7-9) and 22.6% for severe (GMS 10-12) hypospadias (p < 0.001). Degree of chordee was an independent predictor of fistula on multivariate analysis; S4 (>60° ventral curvature) patients were 27 times more likely to develop a fistula than S1 (no curvature) boys (95% CI, 3.2-229). DISCUSSION: The GMS score is based on anatomic features (i.e. glans size/urethral plate quality, location of meatus, and degree of chordee) felt to most likely impact functional and cosmetic outcomes following hypospadias repair. We demonstrated a statistically significant increase in the likelihood of any postoperative complication with every unit increase in total GMS score. The concept that factors aside from meatal location affect hypospadias repair and outcomes is not novel, and degree of ventral curvature and urethral plate quality are often cited as important factors. In our series, boys with greater than 60° of ventral curvature undergoing a single-stage repair were 27 times more likely to develop a fistula than those without chordee on multivariate analysis, making severe curvature an independent predictor of urethrocutaneous fistula formation. That meatal location did not retain significance on multivariate analysis highlights the importance of considering the entire hypospadias complex when determining severity, rather than just evaluating the position of the meatus. Our study has several limitations that warrant consideration. While GMS scores were assigned prospectively, the data was collected retrospectively, subjecting it to flaws inherent with such study design. Furthermore, type of repair is influenced by surgeon preference and subjective assessment of hypospadias characteristics not incorporated in our scoring system (i.e. tissue quality, urethral hypoplasia, penoscrotal transposition). Despite these limitations, our study demonstrates a strong correlation between the GMS classification and surgical complications, furthering supporting its potential as a tool to standardize hypospadias severity and gauge postoperative complications. CONCLUSION: The Glans-Urethral Meatus-Shaft (GMS) classification provides a means by which hypospadias severity and reporting can be standardized, which may improve inter-study comparison of reconstructive outcomes. There is a strong correlation between complication risk and total GMS score. Degree of chordee (S score) is independently predictive of fistula rate.

Early effect of American Academy of Pediatrics Urinary Tract Infection Guidelines on radiographic imaging and diagnosis of vesicoureteral reflux in the emergency room setting.

PURPOSE: In 2011 the AAP revised practice parameters on febrile urinary tract infection in infants and children 2 to 24 months old. New imaging recommendations invigorated the ongoing debate regarding the diagnosis and management of vesicoureteral reflux. We compared evaluations in these patients with febrile urinary tract infection before and after guideline publication. MATERIALS AND METHODS: During 2 separate 6-month periods 350 patients 2 to 24 months old were evaluated in the emergency room setting. Demographics, urine culture, renal-bladder ultrasound, voiding cystourethrogram and admission status were assessed. RESULTS: A total of 172 patients presented with initial febrile urinary tract infection in 2011, of whom 47 (27.3%) required hospitalization, while 42 of 178 (23.6%) were admitted in 2012. Admission by year did not significantly differ (p = 0.423). After guideline revision 41.2% fewer voiding cystourethrograms were done (72.1% of cases in 2011 vs 30.9% in 2012, p <0.001). A 17.2% decrease in renal-bladder ultrasound was noted (75.6% in 2011 vs 58.4% in 2012, p <0.001). Of 55 voiding cystourethrograms 21 (38.2%) were positive in 2012 compared to 36.3% in 2011 (p = 0.809). Mean ± SD maximum vesicoureteral reflux grade was unchanged in 2011 and 2012 (2.9 ± 1.2 and 2.5 ± 0.93, respectively, p = 0.109). There was no association between abnormal renal-bladder ultrasound and voiding cystourethrogram positivity (p = 0.116). CONCLUSIONS: AAP guidelines impacted the treatment of infants and young children with febrile urinary tract infection. We found no relationship between renal-bladder ultrasound and abnormal voiding cystourethrogram, consistent with previous findings that call ultrasound into question as the determinant for additional imaging. Whether forgoing routine voiding cystourethrogram results in increased morbidity is the subject of ongoing study.