Phoenix Children's Hospital

Contrast-enhanced echocardiography (CE-echo) is commonly used in adult patients to optimize endocardial border delineation (EBD) but there is limited experience in children. A prospective, open-label, non-randomized, multicenter study was performed to evaluate the efficacy of intravenous Optison for CE-echo in pediatric patients and determine the optimal dose of Optison. Subjects ≥ 9 and < 18years with suboptimal echocardiograms (defined as ≥ 2 contiguous segments that could not be adequately visualized) were enrolled. After a baseline non-contrast echocardiogram (NC-echo), CE-echo was performed with 2 dose levels of Optison based on patient weight. The primary endpoint was visualization of the LV wall segments (LVWS) in apical 2- and 4-chamber views. An EBD score was calculated by assigning a value from 0 (no visualization) to 3 (optimal visualization) for 12 LVWS. 37 subjects across 8 sites completed the study. 30 had complete echocardiograms at both dose levels. 2 patients had usable images at dose 2 only. Mean age was 13.4years (± 2.6) with 23 males (62%). Mean weight was 73.9kg (± 36.8) with wide distribution of weight (interquartile range of 42-102kg). There were 8 patients under 40kg. Most subjects had a prior medical/surgical history (n = 33, 89%). Both dose levels of Optison CE-echo improved the number of LVWS visualized from 3.7 ± 1.1 on NC-echo to 10.0 ± 0.1 with dose 1 (p < 0.001) and 10.5 ± 0.1 with dose 2 (p < 0.001). EBD score also improved at both dose levels from 11.9 ± 2.5 for NC-echo to 28.5 ± 1.7 for dose 1 (p < 0.001) and 30.2 ± 8.4 for dose 2 (p < 0.001). The number of suboptimal echocardiograms improved from 92.3% ± 10.7 in NC-echo to 26.2% ± 9 with dose 1 (p < 0.001) and 30.8% ± 4.5 with dose 2 (p < 0.001). CE-echo with intravenous Optison in pediatric patients improved the number of LVWS visualized, improved EBD score, and reduced the number of suboptimal echocardiograms at both dosages used in this study. Intravenous Optison can improve LV visualization in pediatric patients with suboptimal echocardiograms.

Surgeons pursuing improvement in the aesthetic outcomes of their cleft lip repairs may benefit from a granular scale evaluating individual objectives of the repair. A working group of 9 surgeons convened to develop an assessment scale for nasolabial aesthetics after unilateral cleft lip repair. The group identified objectives of the repair that could be evaluated using two-dimensional facial photographs. Scale items were developed to appraise success or failure in achieving each objective. Scale items were iteratively tested and refined. The scale was subsequently implemented as part of a Continuing Medical Education course that included self-evaluation and peer-to-peer education, culminating in the formation of individual plans for improvement. Twelve distinct objectives of unilateral cleft lip repair were identified, of which 10 could be evaluated using photographs routinely obtained in clinical practice. A comprehensive scale was developed, incorporating these 10 objectives. Each scale item takes the form of a binary (yes/no) question evaluating a specific aesthetic concept, with accompanying reference images. Intrarater reliability for each item ranged from moderate to substantial (kappa value, 0.57 to 0.81). Interrater reliability ranged from fair to substantial (kappa value, 0.27 to 0.81). When implemented in a Continuing Medical Education course, the scale enabled surgeons to identify specific opportunities for improvement in their repair and specific surgical maneuvers to adopt in pursuit of these improvements. A new scale for evaluating outcomes of unilateral cleft lip repair is presented. The scale provides specific, actionable evaluations for individual objectives of the repair.

Abstract Introduction: Accurate detection and prioritization of tumor-specific somatic variants is foundational to the development of personalized immunotherapies. Traditional pipelines for neoepitope identification rely heavily on short-read next-generation sequencing (NGS) and DNA-based variant calling, followed by RNA expression filtering and HLA-binding prediction. However, this approach is limited by time-intensive workflows, potential false positives from DNA-only calls, and poor capture of complex isoforms or RNA-level editing. Moreover, the accuracy of neoepitope prediction is constrained by conventional sequence-based HLA binding algorithms that do not account for structural and biophysical features of peptide-MHC interactions, particularly across underrepresented HLA alleles. Methods: To overcome these limitations, we developed a streamlined, sequencing-to-vaccine framework that leverages long-read RNA sequencing for direct detection of expressed somatic variants, including fusions, indels, and single nucleotide variants. Using Oxford Nanopore Technologies’ cDNA-PCR approach, we enable comprehensive, full-length transcript characterization from both fresh and frozen breast tumor samples. Our bioinformatic pipeline, NeoTarget, integrates alignment, variant calling, and neoepitope inference from tumor RNA in a single, modular workflow. A core innovation of this pipeline is HLA-Inception, a deep convolutional neural network trained to predict peptide-MHC class I binding using features derived from molecular dynamics-based modeling of electrostatic potential at the peptide-HLA interface, enhancing generalizability across diverse HLA subtypes. Results: Expanding on previous results, the current NeoTarget pipeline identifies, evaluates, and prioritizes single nucleotide variants, indels, and fusions. To validate this system, we used a set of 9 human breast cancer tumors benchmarked with short read sequencing. Identified neoantigens included most variants shown by clinical short read sequencing and also novel structural variants (i.e., fusions) only revealed with long read sequencing with high confidence. Conclusion: Here, we describe the design and performance of the NeoTarget pipeline, and show proof-of-concept feasibility of applying this fast and cost-effective workflow for HLA-restricted epitope discovery in breast tumors using long-read RNA sequencing. Overall, these methods can be applied to rapidly identify and prioritize neoantigens for personalized neoantigen-based immune therapies. Citation Format: F. Batalini, S. Henry, Y. Zhang, R. Foster, J. M. Gayton, A. Hostal, E. A. Wilson, A. Singharoy, M. Gustafson, B. Pockaj, J. Park, K. S. Anderson. Somatic variant detection using long read RNA sequencing reveals HLA-restricted targets for immunotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-06-08.

Tofacitinib is a selective Janus kinase (JAK-1) inhibitor approved for the treatment of ulcerative colitis (UC) in adults. Data is limited in the pediatric population. The aim of this study was to evaluate the efficacy of tofacitinib in pediatric inflammatory bowel disease (IBD). The primary aim was to assess clinical response (categorical improvement in disease activity from baseline) after induction (8-12 weeks). The secondary aims were to assess effectiveness of tofacitinib in achieving corticosteroid-free remission and biochemical response and overall safety. We performed a retrospective multicenter study of pediatric patients with IBD at eight centers across the United States between 2018 and 2023. We collected demographic data, disease classification, prior biologic medication use, laboratory and clinical disease activity, corticosteroid use, adverse events and side effects, and surgical data. Thirty-seven patients were included in this study. Eighteen patients (52.9%) achieved a clinical response within 8-12 weeks, which increased to 20 (58.8%) by 20-28 weeks. Corticosteroid-free remission was achieved by 14 patients (41.2%) by 8-12 weeks, followed by 16 patients (47.1%) at 20-28 weeks. Improvement in albumin and C-reactive protein (CRP) occurred as early as 8-12 weeks. Surgical rate was 10.5% (4/38 patients). Infection was a common adverse effect reported with the use of tofacitinib. This is one of the largest studies evaluating the use of tofacitinib in pediatric IBD in the United States. Our results demonstrate that tofacitinib is an effective treatment for these patients.

Despite the growing use of unsedated transnasal endoscopy (uTNE) in pediatrics, no validated tool exists to assess competence in performing uTNE, hindering effective training and consistent, high-quality performance. Video-based assessment offers a scalable and reliable method for assessing and enhancing procedural skills. Using Delphi methodology, we aimed to identify key competencies and establish content validity evidence for the TransNasal Endoscopy Skills Assessment Tool (TNE-SAT), a video-based tool designed to assess clinician competence in performing uTNE. North American pediatric uTNE experts iteratively rated potential assessment items, on a 5-point scale, based on their importance as indicators of endoscopist competence in performing uTNE. After each voting round, items scoring ≤3/5 were eliminated, and the remaining items were re-sent to the panel for further rating until consensus was reached, defined as ≥80% of panelists rating all remaining items ≥4. Items meeting this threshold were included in the final TNE-SAT tool. Twenty-seven experts from 19 sites across North America participated. One hundred thirty items were generated through literature review, task deconstruction, and Delphi panelist input. Three rounds of surveys were completed before consensus was achieved, with response rates ranging from 85% to 9. Seven items reached consensus for inclusion in the final TNE-SAT. This North American Delphi study identified core competencies required for effective uTNE performance and informed the development of the TNE-SAT, a structured, video-based tool to assess clinician competence. The TNE-SAT offers a promising tool to guide training and support quality improvement in pediatric uTNE.

Children with inflammatory bowel diseases (IBD) have limited access to the available advanced therapies, given the lengthy gap between adult and pediatric approval. We aimed to review key hurdles for pediatric trials and recommend practical solutions. This position paper was developed jointly by the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN and NASPGHAN), in consultation with patient representatives. A systematic review was performed for identified topics, and two voting rounds with two group meetings led to agreement on 24 statements. The systematic review (reviewing 4366 manuscripts, of which 123 were included in tables of evidence and 213 in support of 23 statements) found similar biologic pathogenesis, and similar or better effectiveness and safety in children older than 2 years compared to adults. Pharmacokinetics were similar in adolescents but dissimilar in younger children. The review also found sufficiently accurate noninvasive endpoints to reflect post-induction treatment response. There was no significant added benefit for ileocolonoscopy over sigmoidoscopy in ulcerative colitis. Drugs should be approved in children >12 years and ≥40 kg based on extrapolation from adult and real-world data. While efficacy may be extrapolated to children <40 kg, pharmacokinetics cannot and thus one open-label single-arm study should be performed to establish a dose that matches adult exposure-response from the adult trial in which adolescents may be enrolled if not exposed to placebo. Full colonoscopies should be minimized in the pediatric dosing trial. Efficacy in patients with infantile IBD cannot be extrapolated from adult data.

Nephropathic cystinosis is a rare lysosomal storage disorder characterized by cellular cystine accumulation and progressive multiorgan damage. Before advances in diagnostics, transplantation, and disease-modifying therapy, cystinosis was considered a fatal pediatric disease, with most patients reaching kidney failure by approximately 10 years of age. Life expectancy has now expanded into the 50s and beyond, and the disease has been transformed into a chronic condition with a predominantly extrarenal phenotype in adulthood. Traditionally, nephrologists have played a central role as cystinosis “care quarterbacks” in pediatric settings, and patients often expect this to continue after transitioning to adult care. As such, nephrologists are increasingly tasked with monitoring for and addressing complications in organs other than the kidneys, in addition to coordinating referrals to clinicians within the nephrology clinic (e.g., nurses, advanced practice providers, pharmacists, dietitians, social workers, care coordinators, and transplant specialists) and across multiple specialties (e.g., neurologists, gastroenterologists, endocrinologists, ophthalmologists, and orthopedists). Although recently published expert guidance offers recommendations for the multidisciplinary management of cystinosis, gaps in the literature exist around strategies to reduce care fragmentation, overcome collaboration challenges, and enhance patient/family and clinician experiences. This review aimed to explore various approaches for care delivery optimization across the lifespan of patients with cystinosis as well as improve the current understanding of disease-, patient-, provider-, and system-related factors that influence treatment adherence, engagement, and long-term outcomes.

In the early 1960s, the newborn screening (NBS) program in the United States began with testing for phenylketonuria. Since that time, the NBS program has greatly expanded the number of disorders tested in all newborns. This article reviews the importance of NBS from a public health perspective as well as in the clinical setting to detect, diagnose, and manage conditions early. Current practices vary across the United States as well as internationally. While there have been several advancements in NBS over the past several decades, multiple challenges and limitations remain. Some of these challenges include false-positive and false-negative results, the ethical dilemma of consent, and optimal timing of NBS in the neonatal intensive care unit. Future directions of NBS, both nationally and internationally, include the implementation of next-generation sequencing testing and artificial intelligence.

Minimally invasive repair of pectus excavatum (MIRPE) is among the most painful elective procedures in pediatric patients and is frequently managed with both inpatient and outpatient opioids. However, opioid prescribing practices vary, and evidence-based discharge guidelines are lacking. This study aimed to evaluate outpatient opioid prescribing patterns following MIRPE across multiple institutions. A multicenter retrospective review was performed of patients (<21 years) who underwent MIRPE from 2022 to 2023 across 10 hospitals in the Western Pediatric Surgery Research Consortium. Demographic, operative, inpatient, and outpatient opioid data were collected. All opioid doses were converted to oral morphine equivalents (OME) using standardized conversion factors. Associations between inpatient opioid use and discharge prescriptions were assessed with linear regression. Among 532 patients (85.9 % male; median age 15.5 years [IQR 14.5-17.1]; median Haller index 4.5 [3.8-5.7]), 91 % received intercostal nerve cryoablation. Median hospital length of stay was 1 day [1-2]. Patients were discharged with a median of 10 opioid doses [8-16.5], equivalent to 75 OME [45-120] or 1.32 OME/kg [0.85-2.12]. Discharge prescriptions varied substantially by institution, ranging from 0 [0-10] to 20 [10-20] doses. Discharge OME correlated with inpatient opioid use (β = 0.35, 95%CI 0.26-0.44) and length of stay (β = 20.9, 95%CI 13.4-28.3). Outpatient opioid prescriptions following MIRPE varied widely across hospitals and were positively associated with inpatient opioid use and hospital stay. These findings underscore the need for standardized discharge analgesia guidelines to reduce variability and minimize excess opioid prescribing in pediatric surgical care.