Hospital Of Philadelphia Research Articles

BackgroundInherited hematologic disorders such as sickle cell disease (SCD), thalassemia, and hemophilia are rare but devastating conditions with high morbidity and mortality. Advances in gene therapy have opened curative prospects. The objective of the current study was to provide a comprehensive bibliometric and knowledge-mapping analysis of global research on gene therapy targeting SCD, thalassemia, and hemophilia.MethodsA Scopus-based bibliometric search was conducted for the period from 1986 to 2024. The search used title-specific queries for the target diseases and title-abstract queries for gene therapy technologies. Bibliometric indicators and network visualization maps, created by VOSviewer, were presented.ResultsA total of 1399 articles were retrieved. Publication growth revealed two phases: a steady, but slow phase (1986–2018), and mature expansion phase (2019–2024), with an average annual growth rate of 28% over the last decade. The articles had a mean of 47.6 citations/article and an H-index of 126. Research was mainly distributed across medicine (39.5%), biochemistry/genetics/molecular biology (30.7%), immunology (8.1%), and pharmacology/toxicology (7.5%), reflecting the multidisciplinary nature of the field. The most prolific journal was Blood (8.6%), followed by Hemophilia, Molecular Therapy, Human Gene Therapy, and Blood Advances. The United Stated dominated the field (n = 863; 61.7%), followed by China and the United Kingdom, with the United States showing strong intra-country collaborations, while European countries demonstrated high international collaborations, often with the United States. Leading institutions included the Children’s Hospital of Philadelphia (7.5%) and University of Pennsylvania (5.9%). Co-authorship analysis revealed robust collaboration networks, with notable clusters around AAV-based hemophilia therapy and CRISPR-mediated gene correction for hemoglobinopathies. Keyword co-occurrence highlighted themes like AAV vectors, genome editing, CRISPR-Case9, and ex vivo hematopoietic stem cell modification. Overlay visualization maps indicated a recent surge in CRISPR and clinical applications research.ConclusionsThe bibliometric findings underscore the rapid evolution of gene therapy research for SCD, thalassemia, and hemophilia, moving from experimental approaches to clinical translation. The strong interdisciplinary collaboration, rising clinical trials, and emergence of genome editing tools suggest that the field is entering a transformative era, offering real-world therapeutic solutions for previously incurable inherited blood disorders.

BackgroundObservational studies in adults suggest that incidental PTC (iPTC) and non-incidental PTC (niPTC) are distinct entities. We examine the incidence of iPTC in pediatric patients undergoing thyroidectomy for benign conditions and compare clinical and histopathologic findings, and outcomes, of iPTC with those of niPTC.MethodsA retrospective chart review was conducted at the Children’s Hospital of Philadelphia between August 2010 and February 2023 to identify pediatric patients who underwent thyroidectomy and were diagnosed with pT1a PTC.ResultsiPTC was identified in 23 of 453 (5.1%) patients undergoing thyroidectomy for benign conditions. Within a cohort of 66 patients diagnosed with pT1a PTC, 23 (34.8%) were classified as iPTC and 43 (65.2%) were classified as niPTC. Compared to niPTC, iPTC had a significantly smaller median greatest dimension (iPTC: 3 mm, niPTC: 7 mm, P < 0.001), a lower rate of lymphatic invasion (iPTC: 0%, niPTC: 60.5%, P < 0.001), and AJCC N1 disease (iPTC: 0%, niPTC: 55.8%, P < 0.001). Most iPTC (22 out of 23 (95.7%)) were classified as ATA pediatric low-risk, while six out of 43 (14.0%) niPTC were categorized as intermediate/high-risk. Patients with iPTC and niPTC were followed for a median of 3.3 and 5.7 years, respectively. There was no evidence of persistent or recurrent disease in any patient with iPTC during this time frame.ConclusionsiPTC may be found in 5.1% of pediatric patients undergoing thyroidectomy for benign conditions. Similar to adults, iPTC in pediatric patients appears to be indolent with a minimal risk for invasive features and a low risk for persistent or recurrent disease. In contrast to iPTC, niPTC exhibits the potential for invasive behavior and should be regarded as a distinct entity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease in children. Treatment with glucagon-like-peptide-1 receptor agonists (GLP-1RAs) have shown resolution of steatohepatitis with improvement in fibrosis in adults, yet pediatric studies are extremely limited. This study evaluates the impact of GLP-1RAs on pediatric MASLD, using alanine aminotransferase (ALT) reduction as a marker of improved disease activity. We conducted a single-center retrospective study in patients ≤18 years old with a diagnosis of MASLD, who were prescribed a GLP-1RA from January 2, 2018 and January 10, 2024 at the Children's Hospital of Philadelphia. Data were collected at baseline, 6 months, and at end-of-treatment (EOT). Inclusion required MASLD diagnosis per new criteria, elevated baseline ALT, and paired ALT values at baseline and EOT. Forty-two patients met inclusion criteria (mean age 15 years, 64% male, 55% White). ALT improved by a mean of 56 U/L at 6 months (p = 0.04), and by 37 U/L at EOT (p = 0.004). Patients prescribed a GLP-1RA for type 2 diabetes mellitus (T2DM) had greater reductions in ALT compared to those treated for obesity. Improvements were also observed in aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), glycated hemoglobin (HbA1C), and triglycerides. Body mass index (BMI) percentile and z-score showed no significant changes, but BMI stabilization was observed. This is the largest pediatric study on GLP-1RAs in MASLD to date. On a GLP-1RA, ALT significantly improved at 6 months and EOT, suggesting their role in improving disease activity. This should thus be considered as an adjunct to lifestyle modification in treating pediatric MASLD.

EEG plays an integral part in the diagnosis and management of children with genetic epilepsies. Nevertheless, how quantitative EEG features differ between genetic epilepsies and neurologic outcomes remains largely unknown. In this study, we aimed to identify quantitative EEG biomarkers in STXBP1-related, SCN1A-related, and SYNGAP1-related childhood epilepsy and associated neurologic outcomes. We retrospectively collected clinical scalp EEGs from the Children's Hospital of Philadelphia. After removing artifacts and epochs with excess noise or altered state from EEGs, we extracted spectral features. We validated our preprocessing pipeline by comparing automatically detected posterior dominant rhythm (PDR) with annotations from clinical EEG reports. Next, as a coarse measure of pathologic slowing, we compared the alpha-delta bandpower ratio between controls and patients with different genetic epilepsies. We then trained random forest models with localized spectral features to predict diagnoses of STXBP1, SCN1A, and SYNGAP1 and estimate seizure frequency and motor function across a broader cohort. We evaluated EEGs from individuals with pathogenic variants in STXBP1 (95 EEGs, n = 20; 40% female; mean age 3.98 years), SCN1A (154 EEGs, n = 68; 51% female; mean age 6.24 years), and SYNGAP1 (46 EEGs, n = 21; 57% female; mean age 6.97 years) and neurotypical controls (847 EEGs, n = 806; 55% female; mean age 7.08 years). There was strong agreement between the automatically calculated PDR and annotations from clinical EEG reports (R2 = 0.75). Individuals with STXBP1-related epilepsy had a significantly lower alpha-delta ratio than controls (median Cohen d = -0.95, p < 0.001) across all ages. Models accurately predicted a diagnosis of STXBP1 (area under the curve [AUC] = 0.92), SYNGAP1 (AUC = 0.86), and SCN1A (AUC = 0.85) against controls and each other (accuracy = 0.74). From these models, we isolated highly correlated biomarkers, including the alpha-theta ratio in frontal, occipital, and parietal electrodes associated with STXBP1, SYNGAP1, and SCN1A, respectively. Models were unable to predict seizure frequency (AUC = 0.53). Models predicted motor scores significantly better than age-based null models (p < 0.001). These results suggest that some genetic epilepsies and functional outcome measures have distinct quantitative EEG signatures. Furthermore, EEG spectral features are predictive of some functional outcome measures. Large-scale retrospective quantitative analysis of clinical EEGs has the potential to discover novel biomarkers and to quantify and track individuals' disease progression across development.

Adolescence is a critical period marked by rapid brain development and the onset of many mental health disorders. Brain MRI studies during adolescence, especially when paired with behavioural phenotypes and information about genetic risk factors, hold promise to advance early identification of mental health risk and spur the creation of targeted treatments to improve patient function, prognosis and quality of life. However, prospective neuroimaging is costly and time-intensive, and individuals who participate may not be reflective of the general population. These challenges are compounded when examining adolescents, as many families lack the time, energy or resources to participate in studies that use research-grade imaging. Repurposing clinical MRIs obviates many of the challenges of neuroimaging research. Here, we describe the brain-behaviour-genetics study protocol. This protocol describes procedures used to recruit participants with recent high-quality clinical brain MRIs and prospectively acquire genetic and sociobehavioural data, resulting in a highly cost-efficient design that harnesses a vast and underused neuroscientific resource. The brain-behaviour-genetics protocol aims to recruit 1000 adolescents who have clinical brain MRIs contained in Children's Hospital of Philadelphia's electronic health record. One or both parents of the adolescent proband will be recruited when possible. Parents and adolescents will complete a series of self-report scales spanning the domains of mental health, trauma, risk and resilience. Saliva samples will be collected from the adolescent and at least one biological parent, using an at-home saliva collection kit. Subsequent analysis will examine associations between brain development, genetics and behavioural measures in adolescence. Approval for the study had been obtained from the Children's Hospital of Philadelphia's institutional review board (IRB #23-0 20 851). Results will be published in peer-reviewed journals.

The polygenic risk score genetic quantitative ultrasound speed of sound (gSOS) was developed using machine learning algorithms in adults of European ancestry and associates with reduced odds of fracture in adults. We aimed to determine if gSOS was associated with bone health in children. Two observational studies of children were evaluated: (1) children enrolled in the Bone Mineral Density in Childhood Study (BMDCS) with genetic data (N = 1727); and (2) children with genetic data for research at the Children's Hospital of Philadelphia (CHOP; N = 10 301). Genetic variants were used to calculate gSOS and genetic ancestry. For the BMDCS, puberty stage, dietary calcium, physical activity and fracture accumulation (none or ≥ 1 fracture) were self-reported, height and weight were measured and BMI calculated. Areal bone mineral density (aBMD) of the lumbar spine, hip, radius, and whole body were assessed by dual energy X-ray absorptiometry and expressed as Z-scores. The CHOP study paired genetic data with documentation of fracture in the electronic health record (EHR). gSOS associated with higher aBMD Z-scores across 7 skeletal sites [eg, a 1 SD increase in gSOS associated with 0.17 (95% CI: 0.10-0.24) higher lumbar spine aBMD Z-score]. These associations were consistent for males and females, age, puberty stage, and lifestyle factors, and most consistent among children of European genetic ancestry. A 1 SD increase in gSOS associated with 24% reduced likelihood of self-reported fracture in the BMDCS (OR = 0.76, 95% CI: 0.66, 0.88) and a 12% reduced likelihood of a recorded fracture in the CHOP EHR (OR = 0.88; 95% CI: 0.82, 0.95). No sex or genetic ancestry differences were found. A higher gSOS score associated with higher aBMD at multiple skeletal sites and reduced odds of fracture in two independent pediatric samples. This genetic tool may have clinical utility to help enhance bone health in early life and protect against fracture across the lifespan.

Purpose: Graded exercise training is widely recognized as an effective treatment for reducing symptoms and improving functional capacity associated with postural orthostatic tachycardia syndrome (POTS), a type of acquired dysautonomia. Many clinicians have encountered significant challenges with practical implementation of existing POTS exercise prescription protocols, potentially limiting overall treatment efficacy and negatively affecting outcomes. The purpose of this article is to highlight key principles of exercise treatment in POTS, summarize challenges with current protocols, and describe the newly developed CHOP AADP tools and guides to improve exercise prescription and treatment effectiveness for individuals with POTS. Methods: To address these challenges, the Children's Hospital of Philadelphia (CHOP) Acquired Autonomic Dysfunction Program (AADP) developed novel evidence-based assessment tools and treatment guides using objective data to empower physical therapists in prescribing customizable cardiovascular and strength training programs for this population. Results: The clinical presentation of POTS is complex and heterogenous; using objective measures to guide exercise prescription and customize training programs is therefore imperative to improve exercise tolerance and function. Existing POTS protocols, including the Modified CHOP Protocol, lack sufficient objectivity and customizability. Conclusions: Physical therapists should use objective measures to recommend cardiovascular training duration, position and rate of progression parameters for persons with POTS, specific to individual needs and goals. The CHOP AADP Exercise Determination Tools and Recumbent and Upright Exercise Guides provide clinicians with this objectivity and flexibility.

Abstract Aims To assess the potential for artificial intelligence-enabled electrocardiogram (AI-ECG) to serve as a long-term cardiac surveillance tool and predict left ventricular systolic dysfunction in childhood cancer patients. Methods and Results We assessed performance of our previously established AI-ECG model to predict left ventricular ejection fraction (LVEF) ≤50% and ≤40% in patients with childhood cancer during internal testing (Boston Children’s Hospital) and external validation (Children’s Hospital of Philadelphia). The internal test cohort comprised 447 patients (57% male; age at cancer diagnosis 11.2 [5.4-15.7] years; 1,553 ECG-echo pairs at median age 13.5 [IQR, 7.7-17.9] years; 6.4% with LVEF ≤50%; 1.3% with LVEF ≤40%), 28% with leukemia, 16% with lymphoma, 8% with neuroblastoma, 8% with sarcoma, 2% with gastrointestinal cancers, 3% with genitourinary cancers, 6% with central nervous system cancers, 11% with other/unspecified cancers, and 18% with missing/unknown cancer labels. Treatment strategies included anthracyclines (35%), bone marrow transplant (7%), and radiation (1%). The external test cohort comprised 2,964 patients (55.4% male; 7,054 ECG-echo pairs at median age 11.6 [IQR 6.8-15.1] years; 2.5% with LVEF ≤50%; 0.9% with LVEF ≤40%). Similar AUROCs (0.80-0.85), sensitivities (0.75-0.82), NPVs (0.986-0.996), and percent predicted negative (51-65%) were obtained across institutions to predict LVEF ≤50%, outperforming a biomarker-based model benchmark. Patients with high AI-ECG risk scores for LVEF ≤50% had higher rates of mortality (HR 3.1 [95% 1.8-5.3], p&amp;lt;0.001) compared to patients with low AI-ECG risk scores. Conclusion AI-ECG shows promise as a digital biomarker for cardiac surveillance in the vulnerable childhood cancer survivor population.

Abstract Background Normal Prothrombin Time (PT) and activated partial thromboplastin time (aPTT) values fluctuate in infants &amp;lt;6 months of age due to developmental hemostasis. Because of early alterations in vitamin K levels, PT and aPTT levels that are abnormal in adults could be within the expected range for an infant. PT and aPTT are not harmonized, results can vary among manufacturer platforms, thus instrument specific reference intervals are needed. The objective of this study was to establish reference intervals in infants for PT and aPTT on the Werfen ACL-TOP platform. Methods Results were established using the ACL-TOP instrument with Werfen reagents. Using the electronic medical records, historical patient results were evaluated using ± 2SD to determine a reference interval. Inclusion criteria included age &amp;lt;6 months with available coagulation testing. Exclusion included anticoagulation, congenital heart disease and significant systemic illness. Patient results were sorted by age at time of collection (&amp;lt;6 months) and by year to establish a range for Children’s Hospital of Philadelphia for each year starting in 2021. One hundred patient results were included per year for a total n of 400. All of the data was then combined to establish a total range from 2021-2024 and compared to available reference intervals in the published literature.1-3 Results See attached Jpeg Conclusion Infant reference intervals for the central 95% of the population were determined to be 8.9-16.1 seconds for PT and 24.6-50.1 seconds for aPTT from the years 2021-2024 using historical CHOP data. These data were comparable to data by other instrumentation in other published literature.1-3

Functional ability profiles in beta-propeller protein-associated neurodegeneration (BPAN).

Abstract Corresponding Author Andrew Mudreac, MD, Division of General, Thoracic and Fetal Surgery, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA, (773) 706-1972, mudreaca@chop.edu Funding This work did not receive any funding. Conflict(s) of Interest None of the authors have any conflicts of interest to disclose. Background Perioperative antibiotic use for children undergoing surgical procedures for esophageal and airway disorder treatment (EAT) is highly variable. We developed institutional antimicrobial guidelines for EAT procedures to optimize antibiotic use and reduce variability, but we had not previously evaluated adherence to these guidelines. Methods We conducted a single-center retrospective cohort study to evaluate perioperative antibiotic use for all EAT procedures from 08/2022-11/2024. Procedures were categorized as primary or staged repair of esophageal atresia (EA) or complex EAT procedures (e.g., Aortopexy, Esophageal stricture excision, Esophagectomy, Esophagoplasty, Esophagostomy, Tracheopexy, or Tracheoplasty). The primary outcome was optimal antibiotic choice and duration based on alignment with antimicrobial stewardship recommendations (Table 1). Antibiotics for treatment of a diagnosed infection (e.g., UTI, pneumonia), or surgical complication, such as esophageal leak, or prophylaxis for another condition (e.g., UTI prophylaxis) were considered appropriate. Results Ninety-two cases were included in this study. Of those, 35 (38.0%) were primary EA repair, 24 (26.1%) were staged EA repair, and 33 (35.9%) were complex EAT procedure. Median postoperative antibiotic duration across all groups was 2 days [IQR 1, 6] (Fig. 1). Overall, antibiotic choice and duration was optimal in 45.7% of cases (45.7% in primary repair, 50.0% in staged repair, and 42.4% in complex EAT) (Fig. 2). Pre-operative regimens were more commonly optimal than post-operative: 94.3% vs. 48.6% in primary repair, 70.8% vs. 58.3% in staged repair and 90.9% vs. 42.4% in complex EAT cases. Appropriate intraoperative antibiotics were utilized in 51.1% of cases; piperacillin/tazobactam was selected in the other 48.9% of cases (Table 2). The most common reasons for suboptimal antibiotic selection and/or duration were concern for sepsis without a diagnosed infection and prolonged postoperative surgical prophylaxis. Postoperative infectious complications were rare: one patient developed an SSI and there were no confirmed cases of mediastinitis or postoperative abscess. Conclusion Despite development of an institutional consensus antimicrobial guideline for EAT procedures, there is significant variability in perioperative antibiotic use, particularly during the postoperative period. A targeted multidisciplinary effort to reduce inappropriate perioperative antibiotic usage in EAT patients may be beneficial.

Abstract Corresponding Author Krista Stacey, MD; staceyk@chop.edu Funding None. Conflict(s) of Interest None. Background The optimal antibiotic treatment duration for acute mastoiditis is unknown, with 2-4 weeks recommended by the American Academy of Pediatrics. Methods We performed a comparative effectiveness study of short versus long antibiotic duration in children aged 6 months to 18 years with acute mastoiditis admitted to Children’s Hospital of Philadelphia (CHOP) between January 2016 and December 2023. Children with an ICD-10 diagnosis code for acute mastoiditis were included if they received at least 7 days of antibiotics for clinician-diagnosed mastoiditis and had both clinical and radiographic findings of acute mastoiditis based on physician chart review. Children with severe immunodeficiencies, cochlear implants, chronic mastoiditis (symptoms &amp;gt;1 month), non-bacterial causes of mastoiditis, and those with epidural or subdural abscesses were excluded. The primary exposure was short-course antibiotics, defined as an antibiotic duration of approximately 2 weeks (up to 17 days). The primary outcome was treatment failure, defined as a composite of mastoiditis-related readmission, reoperation, or antibiotic re-treatment within 30 days of completing antibiotic treatment. Antibiotic-associated adverse events were assessed as a secondary outcome. Propensity scores were derived to estimate the probability of receiving short-course antibiotics, then used to generate inverse probability of treatment weights (IPTW). Covariate balance was assessed using standardized mean differences (SMD), with SMD less than 0.1 considered balanced. Weighted logistic regression was then used to calculate odds of treatment failure. Results A total of 126 children were included. Median age was 4 years (IQR, 2, 8 years), 104 (85%) were previously healthy, 53 (43%) had a subperiosteal or subcutaneous abscess, and 66 (52%) underwent a surgical procedure. Sixty-two (49%) received a short duration of antibiotics (median, 14 days; IQR 11, 15 days) and 64 (51%) received a long duration of antibiotics (median 24 days; IQR 21, 28 days). The composite outcome was observed in 7 children (6%), including 2 children (3%) in the short-course group and 5 children (8%) in the long antibiotic duration group (p=.25). Following propensity score weighting, baseline covariates were well-balanced across treatment groups (Fig. 1). The odds of treatment failure with short-course antibiotics in the weighted cohort was 0.49 (95% confidence interval, 0.08-2.96). Antibiotic-associated adverse events occurred more often in the long antibiotic duration group, but this difference did not reach statistical significance (8% versus 16%, p=.18). Conclusion A short duration of antibiotics of approximately 2 weeks was not associated with increased odds of treatment failure relative to a longer duration in children with acute mastoiditis without intracranial complications.

Pediatric cancer and its treatment can negatively affect nutritional status, impacting treatment tolerance, survival, and overall well-being. Poorly managed side effects often lead to lasting poor dietary habits. Caregivers, who bear the psychosocial burden of these effects, are also at risk for diminished health. Interventions that support caregivers' capacity to provide quality care while maintaining their own health are critically needed. Culinary medicine interventions have shown promise in improving cooking confidence, dietary quality, and symptom management. We developed an 8-week culinary medicine intervention, including caregiver coaching, to support pediatric cancer patients and their caregivers. Let's Cook Together is designed to increase caregivers' knowledge of a whole foods dietary approach, improve caregiving preparedness, and boost self-efficacy in managing treatment side effects. Caregivers with children undergoing cancer treatment will be recruited from the Children's Hospital of Philadelphia. The program includes four remote, biweekly cooking sessions led by a medical chef educator and a registered dietitian nutritionist, along with alternating coaching calls focused on caregiving goals and challenges. Participants will also receive written nutrition and cooking resources. This is a single-arm, explanatory sequential mixed-methods feasibility study. Quantitative assessments will be conducted at baseline, post-intervention, and 3-month post-intervention; qualitative interviews will follow the intervention. The primary objective is to assess feasibility and acceptability. Secondary objectives include collecting exploratory outcome data on caregiving preparedness, caregiver self-efficacy, pediatric feeding behaviors, and dietary intake to inform the design and sample size calculations for a future trial and to identify potential signals of intervention effect. Results will inform refinement of the intervention and study design and guide the development of a future trial. Findings may be relevant to oncology and allied health professionals involved in supportive care for families navigating pediatric cancer treatment. ClinicalTrials.gov, NCT06523322, Registered 22 July 2024, https://clinicaltrials.gov/study/NCT06523322 .

Abstract We are pleased to present abstracts from the 15th Annual International Pediatric Antimicrobial Stewardship Conference, held May 29-30, 2025, in St. Louis, Missouri. We hosted nearly 200 attendees, virtually and in-person, including pediatricians, pharmacists, advanced practice providers, and trainees. Our speakers discussed a variety of topics, from diagnostics and treatment of challenging pediatric infectious syndromes to the latest literature in antimicrobial stewardship. We came together to learn how we can best communicate, collaborate and advocate for the health of children. We were fortunate to again welcome our international and fellow awardees as they shared their research and experience in antimicrobial stewardship across the world. We offer our sincerest thanks to those who continue to support us each year, including Cindy Terrill, Lori Barganier, our conference planning committee, Michelle Padgett and the WashU CME team, our sponsors and The Pediatric Infectious Diseases Society. The 16th Annual International Pediatric Antimicrobial Stewardship Conference will be held May 27-29, 2026, in St. Louis, Missouri. We look forward to seeing you then! Evan E. Facer, DO, MS, St. Louis Children’s Hospital, St. Louis, MO; Rebecca G. Same, MD, Children’s Hospital of Philadelphia, PA.

Many refugee children arrive in the USA from regions with higher risks of health conditions such as elevated blood lead or latent tuberculosis, making comprehensive health screening on arrival crucial for child health. Despite Centers for Disease Control and Prevention (CDC) screening guidance, clinical implementation challenges persist. To address this, we developed a clinical decision support (CDS) toolkit to support screening within the Children's Hospital of Philadelphia's refugee health programme. This quality improvement project evaluated the CDS toolkit's effectiveness in improving clinician adherence to screening guidance for newly arrived refugee children across two Plan-Do-Study-Act (PDSA) cycles. We retrospectively evaluated health screening for refugee children aged 6 months to 21 years seen in a primary care-based refugee child health programme from 1 January 2011 to 30 September 2023. We assessed completion of recommended screenings for elevated blood lead level (EBLL), tuberculosis, hepatitis B, anaemia, HIV and eosinophilia. The CDS toolkit was updated during the second PDSA cycle to streamline order sets and align with updated CDC guidance. Screening rates were compared across three periods: baseline, first PDSA cycle and second PDSA cycle. Among 830 refugee children, initial screening completion remained high at 90.12%. Follow-up lead testing improved from 21.46% at baseline to 36.92% in the second PDSA cycle, though 43.08% of eligible children still missed timely follow-up. EBLL prevalence at arrival increased from 7.43% to 15.69%, reflecting changes in screening thresholds and demographics. These findings demonstrate the CDS toolkit's effectiveness in maintaining high initial screening rates while highlighting persistent challenges in follow-up care. The updated CDS toolkit maintained high completion rates for initial screening, and after two PDSA cycles, it correlated with improvements in follow-up testing for EBLL. This project underscores the need for further interventions to improve follow-up care and supports the potential of CDS toolkits to enhance refugee health screening.

Fever following hemispheric disconnection surgery is a well-known, although poorly understood, phenomenon resulting in frequent infectious workups. Prior studies have identified univariate relationships between post-hemispherotomy fever, seizure etiology, and use of an external ventricular drain for temporary CSF diversion. The aim of this study was to examine multivariate relationships between the occurrence of post-hemispherotomy fever, clinical characteristics, and CSF parameters. A retrospective chart review was conducted for all patients who underwent hemispherotomy performed by a single surgeon at the Children's Hospital of Philadelphia from May 2017 to July 2024. Clinical characteristics, including seizure etiology, operative duration, estimated blood loss, age and weight at the time of surgery, and case chronology (i.e., surgeon experience) were abstracted. The daily maximum temperature (Tmax), antipyretic medication dosages, steroid regimen, and all blood and CSF laboratory values were recorded. Fever was defined as Tmax > 38.5°C on postoperative days 0-14. Associations between postoperative fever, clinical characteristics, and CSF parameters were assessed via multivariate logistic regression analysis. Seventy patients (35 male and 35 female, mean age 7.2 years) were included in the analysis. Postoperative fever occurred in 30 patients (42.9%). Fever was more common among patients with Rasmussen's encephalitis (RE; 8/11, 72.7%) and hemimegalencephaly (HME; 5/9, 55.6%), although neither etiology was significant in the multivariate analysis (p = 0.069 and p = 0.097, respectively). Fevers occurred more frequently at the beginning of the surgeon's career and declined with case chronology (OR 0.96, p = 0.047). Among patients for whom CSF laboratory testing was performed (52/70, 74.3%), a significant association was observed between the CSF protein level and postoperative fever (OR 1.002, p = 0.045). The likelihood of fever following hemispherotomy declined with surgeon experience and was positively associated with an elevated CSF protein level. Fevers might also be more common in patients with certain seizure etiologies, specifically RE and HME.

Cerebrovascular pressure autoregulation (CAR) maintains adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. CAR is disrupted after cardiac arrest, making the brain vulnerable to inadequate perfusion and oxygen delivery at population-derived guideline-recommended blood pressures. A metric of CAR can be used to determine the mean arterial pressure (MAP) at which CAR is most preserved, termed the optimal MAP (MAPopt). Our objective was to determine whether deviations above or below personalized CAR-derived MAPopt after pediatric cardiac arrest are associated with outcomes. We conducted a retrospective analysis of prospectively collected data of patients aged 18 years or younger admitted to the pediatric intensive care unit at Children's Hospital of Philadelphia between October 2018 and December 2023 for post-cardiac arrest care. We computed cerebral oximetry index (COx), a metric of CAR, using a moving, linear correlation between time-synchronized brain tissue oxygenation (StO2) from near-infrared spectroscopy and MAP. A multiwindow weighted algorithm determined each patient's MAPopt over time. We compared each patient's MAP with their CAR-derived MAPopt during the first 72 hours after arrest. Unfavorable outcome was defined as a Pediatric Cerebral Performance Category score of 4-6 at hospital discharge with change of ≥1 from baseline. We tested association between burden (combining magnitude and duration) of MAP < MAPopt-5 mm Hg and unfavorable outcome, and between duration of MAP > MAPopt and favorable outcomes using logistic regression models adjusted for age, prearrest developmental disability, and measures of arrest severity. Among 147 patients included (median age 4.5 years, interquartile range [IQR] 1.1-11.7 years, 59% male), 52% had unfavorable outcomes. The median time from return of circulation to data collection was 4 (IQR 2.1-8.3) hours. The median burden of MAP < MAPopt-5 mm Hg was greater for the unfavorable outcome group compared with the favorable outcome group (192 [IQR 114-310] vs 147 [IQR 86-199] mm Hg·min/h, p = 0.002). A 1 SD higher burden of MAP < MAPopt-5 was associated with 2.4 times increased odds of unfavorable outcomes (95% CI 1.24-4.51). Patients with favorable outcomes had a longer duration of MAP > MAPopt than patients with unfavorable outcomes (48% [IQR 38-56] vs 40% [IQR 28-52], p = 0.011). One SD higher duration of MAP > MAPopt was associated with 2.5 times increased odds of favorable outcomes (95% CI 1.20-5.13). Greater burden of MAP < MAPopt-5 mm Hg in the first 72 hours after pediatric cardiac arrest was associated with increased odds of unfavorable outcomes after controlling for potential confounders, and longer duration of MAP > MAPopt was associated with increased odds of favorable outcomes.

In March of 2025, 145 attendees convened at the Hub for Clinical Collaboration of the Children's Hospital of Philadelphia for the inaugural International Society for Magnetic Resonance in Medicine (ISMRM) Body MRI Study Group workshop entitled "Body MRI: Unsolved Problems and Unmet Needs." Approximately 24% of the attendees were MD or MD/PhD's, 45% were PhD's, and 30% were early-career trainees and postdoctoral associates. Among the invited speakers and moderators, 28% were from outside the United States, with a 40:60% female-to-male ratio. The 2.5-day program brought together a multidisciplinary group of scientists, radiologists, technologists, and trainees. Session topics included quantitative imaging biomarkers, low- and high-field strengths, artifact and motion correction, rapid imaging and focused protocols, and artificial intelligence. Another key session focused on the importance of team science and allowed speakers from academia and industry to share their personal experiences and offer advice on how to successfully translate new MRI technology into clinical practice. This article summarizes key points from the event and perceived unmet clinical needs within the field of body MRI.

BackgroundTransitioning from pediatric to adult sickle cell disease (SCD) care is challenging for emerging adults (aged 17-25 years). This period is marked by a 7-fold increase in mortality rates and has the highest rates of hospitalizations, emergency room visits, and hospital readmissions compared with children living with SCD. These challenges are exacerbated by fragmented care coordination, difficulty navigating adult health care systems, and increased self-management responsibilities.ObjectiveThis study aims to compare the effectiveness of 2 interventions designed to support emerging adults living with SCD during this transition: a mobile health (mHealth) app and community health worker (CHW) support to standard care.MethodsThe Community Health Workers and Mobile Health for Emerging Adults Transitioning Sickle Cell Disease Care (COMETS) trial is an ongoing multicenter, 3-arm, open-label randomized controlled trial; 375 emerging adults (aged 17-25 years) are being enrolled and randomized 1:1:1 to (1) a 6-month CHW intervention focused on self-management skills, symptom tracking, care coordination, and transition planning; (2) a 6-month mHealth self-management program (enhanced iManage application) with tailored SMS text messaging (THRIVE [Texting Health-Related Resources to Inform, Motivate, and Engage] 2.0); or (3) enhanced usual care (control). Participants are followed for 18 months. The primary outcome is the change in self-reported health-related quality of life assessed using the PedsQL SCD module. Secondary outcomes include acute care use (hospitalizations and emergency department visits), patient activation, self-management behavior, and successful transfer to adult hematology care.ResultsThe institutional review board at Children’s Hospital of Philadelphia approved this study in June 2018. Recruitment began in January 2019 and ended in December 2022; we completed data collection in November 2024. We have enrolled a total of 405 participants.ConclusionsThis trial addresses a critical gap in transition intervention research for young adults with SCD. It will provide evidence on the comparative effectiveness of 2 promising interventions (CHW and mHealth) and inform the development of scalable and sustainable transition support programs. Findings will have implications for improving health-related quality of life, reducing acute care use, and promoting successful transition to adult-centered SCD care for this vulnerable population.Trial RegistrationClinicalTrials.gov NCT03648710; https://clinicaltrials.gov/study/NCT03648710International Registered Report Identifier (IRRID)DERR1-10.2196/69239

Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in infancy. Caregivers often experience significant challenges in caring for these medically complex children. The purpose of this study was to determine feasibility of administering an electronic social determinants of health (SDoH) screening tool and to determine if caregiver social needs correlate with respiratory outcomes in children with BPD. An SDoH screening tool was completed by caregivers of children seen in BPD pulmonary clinics at the Children's Hospital of Philadelphia (2022-2025). Subject characteristics and respiratory health outcomes were obtained by chart review and questionnaires. Approximately 1/3 of caregivers (34.7%) endorsed a social need, with difficulty paying utility bills the most expressed need. Children of caregivers who endorsed at least one social need were more likely to have lower birth weights, earlier gestational ages, and caregivers who self-report as Nonwhite. For every social need identified, there was a 32% increased risk of an emergency department visit and a 38% increased risk of rehospitalization (unadjusted). When analyzed by self-reported race, children of White but not Nonwhite caregivers, had twice the likelihood of an ED visit/rehospitalization with each social need endorsed. Social need endorsement is high in caregivers of children with BPD. An association between social need endorsement and ED visits/re-hospitalizations was found in children of self-reported White but not Nonwhite caregivers, suggesting that other systemic issues not identified by the SDoH tool account for the high acute care events in children of Nonwhite caregivers.