Phoenix Children's Hospital is a freestanding pediatric acute care children's hospital located in Phoenix, Arizona. The hospital has 457 pediatric beds and is affiliated with the University of Arizona College of Medicine – Phoenix. Phoenix Children's also partners with Valleywise Health (formerly the Maricopa Integrated Health System) for a 3-year pediatric residency training program. The hospital provides comprehensive pediatric specialties and subspecialties including inpatient, outpatient, emergency, trauma, and urgent care to infants, children, teens, and young adults 0–21 throughout Arizona and the surrounding states. The hospital sometimes also treats older adults that require pediatric care. Phoenix Children's Hospital also features a Level 1 Pediatric Trauma Center, the only in the state. The hospital is one facility within Phoenix Children's statewide pediatric health system. Additional locations include Phoenix Children's Hospital–East Valley at Dignity Health Mercy Gilbert Medical Center, four pediatric specialty and urgent care centers, 11 community pediatric practices, 20 outpatient clinics, two ambulatory surgery centers and seven community-service-related outpatient clinics. Phoenix Children's Care Network includes more than 1,175 pediatric primary care providers and specialists who deliver care across more than 75 subspecialties.
Background:Atypical teratoid rhabdoid tumor (ATRT) is a rare pediatric central nervous system tumor with little data on the efficacy of upfront treatment strategies. This study reports prognostic factors and survival of children with newly diagnosed ATRT at high-volume centers treated as per the Children's Oncology Group trial ACNS0333. Methods:Data were collected retrospectively from 13 institutions. Included subjects were children with newly diagnosed ATRT, treated as per ACNS0333, a single-arm phase III trial of intensive chemotherapy and radiation therapy (RT). Data were analyzed to assess the prognostication of clinical variables and estimates of event-free survival (EFS) and overall survival (OS). Results:Eighty subjects were included, with a median age at diagnosis of 18 months, 70% had localized disease, and 53% underwent complete tumor resection at the time of diagnosis. Fifty patients (63%) completed all therapy phases, while 12 patients (15%) experienced progression during treatment. Fifty-three patients (66%) received post-induction consolidation with high-dose chemotherapy and stem cell rescue (HDC/SCR), and 55 (69%) received RT. The 4-year EFS and OS for the entire cohort were 49% and 53%, respectively. Patients completing all therapy phases had superior outcomes (4-year EFS: 63%; OS: 67%). Absence of disease post-induction correlated with improved outcomes (4-year EFS: 64%; OS: 70%), and patients with primary spinal cord tumors had poor outcomes despite intensive therapy. Conclusions:Children with ATRT treated as per ACNS0333 with multi-modal therapy, including HDC/SCR and RT, have improved survival compared to those treated without RT and is higher than previously reported on study.
Introduction Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies ( N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. Objective FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. Design FIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m 2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021–002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. Conclusion FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. Trial registration ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.
BACKGROUND:Approved pharmacologic therapies for pediatric hypertrophic cardiomyopathy are lacking, and surgical intervention may be indicated in patients with left ventricular outflow tract obstruction. The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents. METHODS:We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving symptomatic adolescents (12 to <18 years of age) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy. The patients were randomly assigned in a 1:1 ratio to receive mavacamten or placebo. The primary end point was the change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver. RESULTS:A total of 44 patients underwent randomization; 23 patients (8 [35%] of whom were female) were assigned to mavacamten group, and 21 (5 [24%] of whom were female) were assigned to the placebo group. The mean (±SD) age of the patients was 14.7±1.7 years in the mavacamten group and 14.6±1.7 years in the placebo group, and the mean Valsalva left ventricular outflow tract gradient at baseline was similar in the two groups (78.4±34.1 mm Hg and 80.8±47.4 mm Hg, respectively). At week 28, the least-squares mean change in the Valsalva left ventricular outflow tract gradient was -48.5 mm Hg in the mavacamten group and -0.5 mm Hg in the placebo group (difference, -48.0 mm Hg; 95% confidence interval, -67.7 to -28.3; P<0.001). The incidence of adverse events was similar in the two groups. Two patients in each group had serious adverse events; in the mavacamten group, 1 patient had two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter-defibrillator; in the placebo group, 1 patient had chest pain, and another had depression with suicidal ideation. No patient had a reduction in the left ventricular ejection fraction to less than 50%. No deaths occurred during the trial. CONCLUSIONS:Among adolescent patients with obstructive hypertrophic cardiomyopathy, the reduction in left ventricular outflow tract obstruction was significantly greater with mavacamten than with placebo over a 28-week period. (Funded by Bristol Myers Squibb; SCOUT-HCM ClinicalTrials.gov number, NCT06253221.).
To characterize national patterns of ocular trauma related to pickleball, dodgeball, and kickball in the United States, with emphasis on incidence, demographics, injury mechanisms, and diagnoses. Data from the U.S. Consumer Product Safety Commission’s National Electronic Injury Surveillance System (2014–2023) were reviewed. Injury cases were identified using body part codes for the eye, face, and head combined with product code 3235 (“Other Ball Sports”). Trauma narratives were subsequently manually reviewed to confirm sport involvement alongside ocular and/or orbital injury. National injury estimates were calculated using the NEISS-provided sample weights. Annual incidence per million people was calculated using data from the U.S. Census Bureau and American Community Survey. Statistical analyses included descriptive statistics and inferential testing using chi-square tests, ANOVA, and linear regression. A total of 120 confirmed cases were identified, corresponding to an estimated 7974 ocular injuries (95
Background The Kasai portoenterostomy (KPE) is the only option to achieve native liver survival for patients with biliary atresia and yet technical variations exist. We surveyed members of three American pediatric surgery research consortia regarding their approach to the KPE. Methods Members from the Eastern Pediatric Surgery Network (EPSN), Midwestern Pediatric Surgery Consortium (MWPSC), and Western Pediatric Surgery Research Consortium (WPSRC) developed the survey which was distributed via REDCap to consortia member institutions. Results The survey was completed by 44/45 institutions. KPE is performed by pediatric surgeons at 41 sites (93%), a transplant surgeon at one (2%), and both at two (5%). Twenty-six sites (59%) transected into the liver capsule, 10 (23%) into the liver, two (5%) into the fibrous cord, and 6 (14%) reported variance. One site (2%) reported use of cautery in addition to sharp dissection for porta hepatis transection. The most common length for the Roux limb was 25-35 cm (16, 36%), with 14 sites (32%) creating a Roux limb < 25 cm, eight sites (18%) > 35 cm, and 6 sites (14%) responding that length varies between surgeons. Surgical diagnosis with intraoperative cholangiogram (IOC) was always performed at 33 sites (75%), and twenty-eight sites (64%) obtain both preoperative percutaneous and intraoperative biopsies. Two sites (5%) offer partially laparoscopic KPE. Conclusion In the first survey of American surgical practices for KPE, we found consensus regarding some technical aspects of the operation. However, the responses to most questions demonstrated variability. Future studies will analyze how technical variations impact national KPE outcomes.
