Children’s Hospital Of Philadelphia Research Articles

Invasive Fungal Disease in Pediatric Heart Transplant Recipients

Abstract Background The epidemiology of IFD following pediatric heart transplantation (pHT) is poorly characterized. We sought to evaluate use of antifungal prophylaxis and describe the epidemiology of IFD in pHT at two large children’s hospitals. Methods We performed a retrospective cohort study of pediatric and young adult (≤21 years) patients undergoing heart transplantation at Cincinnati Children’s Hospital Medical Center (CCHMC) and Children’s Hospital of Philadelphia (CHOP) between 2012 and 2021. We recorded demographic, clinical, medication, and laboratory data for pHT patients through 12 months post-transplant. We identified use of topical (oral nystatin) and systemic antifungal prophylaxes in the peri-transplant period (7 days prior through 14 days following transplant) and analyzed if certain transplant variables were associated with the administration of systemic antifungals during this period using rank sum and chi squared tests. Applying published definitions, we quantified the incidence of proven and probable IFD and explored the characteristics of these cases. Results A total of 201 patients underwent heart transplant at CCHMC and CHOP. The majority were male (60.2%), White (66.7%), and not Hispanic or Latino (88.1%). Median age at time of transplant was 7.4 years (IQR 0.9-14.2). During the peri-transplant period, 143 (71.1%) patients received oral nystatin and 37 (18.4%) received systemic antifungal prophylaxis, not including PJP prophylaxis. 41 individuals (20.4%) were not on any antifungal prophylaxis throughout this period. Delayed chest closure was significantly associated with the administration of systemic antifungals (p<0.001) while several other variables (age, hospital, immunosuppression medication, ECMO/LVAD pre-transplant) were not. In total, 8 patients (4%) developed proven (n=5) or probable (n=3) IFD. In our cohort, the incidence rate of proven/probable IFD in the first year post-transplant was 44.8 per 1000 patient-years. The characteristics of these cases are shown in Table 1. Time from pHT to IFD ranged from 11 days to 196 days (median time = 25.5 days). All cases of proven IFD occurred within 28 days of transplant. In three cases of proven/probable IFD, patients were receiving a systemic antifungal or PJP prophylaxis in the seven days prior to IFD onset. Two cases met the definition of probable IFD but the infections resolved without directed therapies. Four patients with proven IFD died within 1 year following transplant, although in only 3 cases was IFD a contributing factor. The one-year all-cause mortality rate among pHT patients with proven/probable IFD (50%) was higher than that in pHT patients without IFD (10.3%; Fisher’s exact p=0.008). Conclusion Over a 10-year period at CCHMC and CHOP, 4% of pHT patients developed proven or probable IFD within one-year post-transplant. All proven IFD cases occurred within a month of transplant while probable cases occurred more than 100 days post-transplant. Delayed chest closure was significantly associated with the administration of systemic antifungal prophylaxis. Patients with proven IFD had poor outcomes despite receipt of appropriate antifungal treatment. Given the low incidence of IFD at these two centers, we were unable to evaluate risk factors for IFD in this population and so larger studies would be needed.

Abstract 1249: cBioPortal for Cancer Genomics

Abstract cBioPortal for Cancer Genomics is an open-source platform for interactive, exploratory analysis of large-scale clinico-genomic data. cBioPortal provides a suite of user-friendly visualizations and analyses, including OncoPrints, mutation lollipop plots, variant interpretation, group comparison, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization. The public site (https://www.cbioportal.org) is accessed by >35,000 unique visitors each month and hosts data from >390 studies spanning individual labs and large consortia. All data is available in the cBioPortal Datahub: https://github.com/cBioPortal/datahub; in 2023 we added 35 studies (~16,000 samples). In addition, >86 instances of cBioPortal are installed at academic institutions and companies worldwide. We also host a dedicated instance for AACR Project GENIE, enabling access to the GENIE cohort of >197,000 clinically sequenced samples from 19 institutions (https://genie.cbioportal.org). The GENIE Biopharma Collaborative (BPC) enables the collection of comprehensive clinical annotations including response, outcome, and treatment history, which can all be visualized in cBioPortal. BPC cohorts for non-small cell lung cancer (~2,000 samples) and colorectal cancer (~1,500 samples) are available, with more cancer types to come. This past year, we significantly enhanced existing features. Group comparison now includes a Mutations tab showing a mirrored lollipop plot and outcomes analysis now supports hazard ratios and landmark analysis. Arm-level copy number can now be compared across groups, as can any data in the generic assay format. We also enhanced the study view. Users can now add charts to summarize the copy number of a specific gene across the cohort. The option to add custom data charts now supports numerical data as well as categorical data. Filters in study view can now be manually submitted, which provides a performance improvement when applying multiple filters in a large cohort. Larger-scale performance improvements are currently underway. We continue to improve support for multimodal datasets incorporating derived data elements, including cell type counts and fractions per sample from imaging or single cell data. The MSK-SPECTRUM ovarian cancer study has samples profiled with bulk sequencing, scRNASeq, H&E and mpIF imaging. Through integrations with CELLxGENE (single cell data) and Minerva (imaging), users can explore these data modalities in detail in isolation and query them jointly in cBioPortal. cBioPortal is open source (https://github.com/cBioPortal/). Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Childrens Hospital of Philadelphia, Princess Margaret Cancer Centre, Caris Life Sciences, Bilkent University and The Hyve. We welcome open source contributions from others in the cancer research community. Citation Format: Tali Mazor, Ino de Bruijn, Rima AlHamad, Calla Chennault, Corey Dubin, Jeremy Easton-Marks, Zhaoyuan Fu, Benjamin Gross, Charles Haynes, David M. Higgins, Jason Hwee, Prasanna K. Jagannathan, Mirella Kalafati, Karthik Kalletla, James Ko, Tim Kuijpers, Sowmiyaa Kumar, Priti Kumari, Ritika Kundra, Bryan Lai, Xiang Li, James Lindsay, Aaron Lisman, Qi-Xuan Lu, Ramyasree Madupuri, Angelica Ochoa, Yusuf Z. Özgül, Oleguer Plantalech, Matthijs N. Pon, Baby A. Satravada, Jessica Singh, Selcuk Onur Sumer, Pim van Nierop, Floris Vleugels, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, Nikolaus Schultz. cBioPortal for Cancer Genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1249.

Doppler Finding, Cardiovascular Function Assessment, and Fetuses' Survival Following the Fetoscopic Laser in Twin-to-Twin Transfusion Syndrome.

Introduction: This study aimed to evaluate the effectiveness of selective laser photocoagulation of communicating vessels (SLPCV) on cardiac function in twins with twin-to-twin transfusion syndrome (TTTS). Methods: This retrospective cohort study evaluated 178 women with twin pregnancies complicated with TTTS and scheduled for SLPCV between 16 and 26 weeks of gestation. The severity of TTTS was determined by Quintero staging and the severity of cardiovascular disorders by the CHOP (Children's Hospital of Philadelphia) score. Patient survival was evaluated through a one-month-after-birth follow-up of fetuses. Results: The study revealed significant improvements in Doppler indices in both donors and recipients after SLPCV. The CHOP score also significantly decreased after the intervention. One-month-after-birth survival rates were 55.1% in donors and 56.7% in recipients. Some Doppler indexes of fetuses before SLPCV could predict survival until one month after birth. Conclusion: The study suggests that SLPCV can improve cardiac function in fetuses with TTTS and that some Doppler indexes can predict survival outcomes. Additionally, the severity of TTTS can be a powerful indicator of the severity of cardiovascular complications.

Evaluating the Utility of a New Pathogenicity Predictor for Pediatric Cardiomyopathy

Pediatric cardiomyopathy (CM) has significant childhood morbidity and mortality which is caused by both genetic and environmental factors. Previous research has focused on identifying genetic variants in pediatric CM for diagnostic purposes, but not for risk stratification. The current study was modeled after previous work which showed an association between CardioBoost-classified disease-causing variants and an increased risk for severe clinical outcomes in adults with CM to assess if the same association is true in pediatric CM. This was a retrospective, single-center cohort study that evaluated outcomes in pediatric CM patients who were evaluated by the Children’s Hospital of Philadelphia (CHOP). CardioBoost (CB) scores were generated for these patients, and scores were categorized as ≤0.1, 0.1-0.9, and ≥0.9. Composite endpoint was freedom from a major adverse cardiac event (MACE). 104 patients were included in the final analysis. 32 (31%) had DCM, 45 (43%) had HCM, and 27 (26%) had other CM. There was no significant association between CB score and clinical outcome in pediatric CM patients. Overall, this study highlights the continued deficits in variant interpretation for pediatric CM. We recommend using caution when applying this tool to stratify clinical outcomes in the pediatric population.

METB-08. GENOMIC AND MOLECULAR PROFILING OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE INSTITUTION ANALYSIS

Abstract BACKGROUND Molecular characterization has revolutionized management of pediatric central nervous system (CNS) tumors, with genomic sequencing for diagnosis and determination of actionable variants now largely considered standard of care. We report a single institution’s experience performing genomic sequencing for pediatric CNS tumors over nearly five years. METHODS Nucleic acid isolated from tumor tissue and paired normal specimens from patients at Children’s Hospital of Philadelphia (CHOP) undergoes paired next generation sequencing (NGS) and copy number analyses of 237 cancer genes and a fusion panel of more than 700 exons of 117 cancer genes (tumor only). All variants are tiered 1-4 according to known clinical significance. Descriptive statistics summarize clinical and molecular data and ensemble-based methods will be used to correlate molecular and clinical characteristics. RESULTS Between January 1, 2016 and June 30, 2020, 497 patients ≤ 21 years old with median age of 9.5 years (n=243 females; 49%) contributed to 539 cases across 25 CNS tumor subtypes. The most common diagnoses were pilocytic astrocytoma (n=118), medulloblastoma (n=49), and diffuse midline glioma (DMG; n=39). Clinically significant variants (tier 1,2) were detected in 91% of the patients. Most tumors demonstrated tier 1,2 single nucleotide variants (SNV)/insertions/deletions (n=263, 53%), most commonly in TP53>BRAF>H3F3A, and/or CNVs (n=310, 62%), most commonly gains of 7q>7p>1q. Thirty percent of tumors demonstrated tier 1,2 fusions (n=149), most commonly involving BRAF, NTRK2, or FGFR. Average tumor mutation burden in patients without germline predispositions was 3.5/Mbp (standard deviation 3.8). Germline/presumed germline pathogenic variants were found in 18% (90/497) of patients tested with most common germline alterations in TP53 followed by NF1 and APC. CONCLUSION A large, single site cohort of molecularly characterized CNS tumors demonstrate the clinical and biologic utility of real-time, institution-based genomic sequencing. Molecular findings in correlation with clinical characteristics and outcomes are underway.

Late Survival after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease in a Single-Center Cohort

Chronic granulomatous disease (CGD) is an inborn error of immunity associated with significant morbidity and mortality for which hematopoietic stem cell transplant (HSCT) is a definitive treatment. In a large single-center cohort, we examined the late survival (survival at 5 years post-HSCT) of all patients who underwent HSCT for CGD at the Children’s Hospital of Philadelphia (CHOP).

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient

A vascularized composite tissue allotransplantation (VCA) was performed at the Children’s Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at “hand areas”, reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip’s somatosensory response.

Global research trends in bone mineral density in children with diabetes: a bibliometric and visualization study

Research on bone density in children with diabetes has attracted increasing attention, and this study aims to investigate the global status and trends in this field.From the Web of Science's Science Citation Index, research papers related to bone density in children with diabetes from 1984-2022 were retrieved. Source data were studied and indexed using bibliometric methods. The visualization study used VOS viewer software for literature coupling, co-authorship, co-citation and co-occurrence analysis to analyze the publication trend of bone density in children with diabetes.A total of 1074 articles were included. Globally, the number of related research interests and publications is increasing every year. The United States contributes the most to global research, receives the most citations, and has the highest h-index. The Journal of Clinical Endocrinology and Metabolism has the highest number of publications.The university of pennsylvania,Childrens hospital of philadelphia,Pennsylvania medicine,Harvard university and university of Sydney are the largest contributors. Research can be divided into four categories: mechanistic research, animal research, clinical trials, and tissue engineering. Mechanism research is expected to be the next hot topic in this field.From the current global research trend, the number of papers on bone density in children with diabetes will continue to increase. The United States is the largest contributor in this area. Much of the effort is devoted to the mechanisms of changes in bone density in children with diabetes, which could be the next hot spot in research.

858: THE IMPLEMENTATION OF A HEALTH EQUITY CURRICULUM IN A PEDIATRIC CRITICAL CARE FELLOWSHIP

Introduction: Bias and racism in medicine perpetuate health disparities. In response, the Accreditation Council for Graduate Medical Education has instituted program requirements to address diversity, equity, and inclusion (DEI) in training programs. Little guidance has been given regarding the structure and content of these curricula. As such, we aim to describe the structure and function of an integrated health equity curriculum at the pediatric critical care medicine (PCCM) fellowship program at the Children’s Hospital of Philadelphia (CHOP) and present our curriculum as a model for other training programs. Methods: Attendings, fellows, research assistants, and administrators serve on the Health Equity Committee (HEC). HEC is divided into three domains: education, research, and community engagement. Education topics include understanding institutional racism in medicine, mitigating bias and microaggressions, and local patterns of disparate outcomes (i.e. violence, asthma, etc). The research domain incorporates health equity into research and quality improvement projects. The community engagement domain is involved in patient education in Philadelphia and recruitment initiatives for medical students who are underrepresented in medicine. Results: Over the first 24 months, HEC has conducted nine lectures, four journal clubs, three health equity case conferences, and an interactive session regarding a structured response to microaggressions. Nationally, HEC directed a PCCM survey to assess diversity engagement across fellowship programs and identify areas for improvement; locally, HEC is working to improve the utilization of interpreters and partnering with CHOP’s Center for Health Equity to increase CPR teaching in Philadelphia. Most importantly, HEC activities are fully integrated into existing fellow education with high expectations for participation and accountability. Conclusions: The CHOP PCCM HEC is a feasible and generalizable model for implementing a DEI curriculum. HEC fosters an environment that integrates DEI into the education of pediatric critical care fellows. Integrating DEI-focused education, research, and community engagement sustainably modeled by HEC can contribute to the elimination of disparities and bias in the care of critically ill children.

Health Care as a Partner in Federal Nutrition Programs: Call for Advocacy.

Health Care as a Partner in Federal Nutrition Programs: Call for Advocacy.

Alternative technique of intrauterine myelomeningocele repair to decrease the incidence of unfavorable maternal and fetal outcomes.

The aim of the study was to determine the effectiveness of an alternative method of open fetal surgery to prevent severe unfavorable prenatal events, both for the mother and the fetus. In this study, the previously published results for a cohort of 46 patients, who had undergone intrauterine myelomeningocele repair (IUMR) at our Center by 2014, constituted the retrospective control group (CG). The MOMS protocol had been applied for hysterotomy, with an automatic uterine stapling device. The study group (SG) n = 57 was assembled during a prospective observation. IUMR was performed using an alternative method of hysterotomy, with the typical opening and closure of the uterus, without automatic stapling device, as described by Moron et al. Additionally, our single-center results were compared with the post-MOMS findings of other centers: CHOP (Children' S HOSPITAL OF PHILADELPHIA: ) and VUMC (Vanderbilt University Medical CENTER: ). No cases of delivery before 30 weeks of gestation (0%, 0/55) were observed in the study group, which is a statistically significant difference (p < 0.05) as compared to controls (15/44). Statistically significantly lower incidence of chorioamniotic separation (5.4% (3/55) vs CHOP 22.9% (22/96), p < 0.001) and contractile activity resulting in preterm labor (16.3% (9/55) vs CHOP 37.5% (36/96), p < 0.05) was found in the study group. Premature rupture of the membranes was statistically significantly less common in the study group as compared to controls, CHOP and VUMC (SG 12.7% (7/55) vs CG 52.2% (24/46), p < 0.001; vs CHOP 32.3% (31/96), p < 0.001; vs VUMC 22% (9/43), p < 0.01, respectively). The presented IUMR method is associated with improved perinatal outcomes, i.e., lower rates of preterm delivery at < 30 weeks of gestation, preterm premature rupture of membranes, and uterine contractility resulting in preterm delivery. That, in turn, results in lower prematurity rates and, consequently, more favorable neonatal outcomes.

Bone Mineral Density and Current Bone Health Screening Practices in Friedreich's Ataxia.

IntroductionFriedreich’s Ataxia (FRDA) is a progressive neurological disorder caused by mutations in both alleles of the frataxin (FXN) gene. Impaired bone health is a complication of other disorders affecting mobility, but there is little information regarding bone health in FRDA.MethodsDual energy X-ray absorptiometry (DXA) scan-based assessments of areal bone mineral density (aBMD) in individuals with FRDA were abstracted from four studies at the Children’s Hospital of Philadelphia (CHOP). Disease outcomes, including the modified FRDA Rating Scale (mFARS), were abstracted from the FRDA Clinical Outcomes Measures Study (FACOMS), a longitudinal natural history study. A survey regarding bone health and fractures was sent to individuals in FACOMS-CHOP.ResultsAdults with FRDA (n = 24) have lower mean whole body (WB) (–0.45 vs. 0.33, p = 0.008) and femoral neck (FN) (–0.71 vs. 0.004, p = 0.02) aBMD Z-scores than healthy controls (n = 24). Children with FRDA (n = 10) have a lower WB-less-head (–2.2 vs. 0.19, p < 0.0001) and FN (–1.1 vs. 0.04, p = 0.01) aBMD than a reference population (n = 30). In adults, lower FN aBMD correlated with functional disease severity, as reflected by mFARS (R = –0.56, p = 0.04). Of 137 survey respondents (median age 27 y, 50% female), 70 (51%) reported using wheelchairs as their primary ambulatory device: of these, 20 (29%) reported a history of potentially pathologic fracture and 11 (16%) had undergone DXA scans.ConclusionsLow aBMD is prevalent in FRDA, but few of even the highest risk individuals are undergoing screening. Our findings highlight potential missed opportunities for the screening and treatment of low aBMD in FRDA.

90. Deimplementation: Use of Electronic Clinical Decision Support to Reduce Unnecessary Erythrocyte Sedimentation Rate (ESR) Ordering

Abstract Background In recent years, several de-implementation initiatives have focused on diagnostic testing. One such initiative, the Choosing Wisely campaign, recommends against routine use of erythrocyte sedimentation rate (ESR) for assessment of acute undiagnosed inflammation or infection. With the development of newer biomarkers of inflammation, particularly C-reactive protein (CRP), there is a decreasing role for ESR in screening for acute-onset conditions; however, ESR continues to be commonly ordered. Methods We examined ESR and CRP ordering practices at the Children’s Hospital of Philadelphia (CHOP) from July 2019 to July 2020 and found that 80% of ESR orders were placed concurrently with an order for CRP. We aimed to reduce ESR ordering by 20% at CHOP by using electronic clinical decision support in the form of embedded order guidance for ESR orders placed in the Emergency Department (ED) and inpatient setting. We examined the effect of the clinical decision support by assessing ESR ordering rate, defined by ESR orders per monthly patient days for the inpatient setting and ESR orders per monthly ED visits for the ED setting. We then examined differences in ordering rates using a quasi-experimental model with a concurrent control (basic metabolic panel). ESR Electronic Clinical Decision Support Intervention Inpatient and ED versions of the embedded electronic clinical decision support for ESR orders. Results Prior to implementation of the electronic decision support intervention, the median monthly rate of ESR orders was 13.6 per 1000 patient days and 70.3 per 1000 ED visits. During the initial month after implementation, we found that ESR ordering was 12.5 in inpatient and 46.4 in ED, reflecting decreased rates of ordering. The median monthly rate of basic metabolic panel orders (concurrent control) was 194.5 per 1000 patient days and 110.0 per 1000 ED visits. This was unchanged after intervention. Conclusion We conclude that electronic clinical decision support is a potentially effective deimplementation method for improving diagnostic test utilization, even with non-disease specific testing such as inflammatory markers. However, continued post-implementation data monitoring and analysis is needed to determine if this is a true difference and sustainable trend. Disclosures All Authors: No reported disclosures

CT Trends After Minor Head Injury Guideline Implementation

Source: Corwin DJ, Durbin DR, Hayes KL, et al. Trends in emergent head computed tomography utilization for minor head trauma after implementation of a clinical pathway. Pediatr Emerg Care. 2021;37(9);437-441; doi:10.1097/PEC.0000000000001728Investigators from the Children’s Hospital of Philadelphia (CHOP), Philadelphia, PA, conducted a retrospective study to assess changes in neuroimaging among children seen in the ED for mild traumatic brain injury (TBI) following implementation of guidelines designed to reduce unnecessary CT scans. The guidelines, implemented in 2011, were adapted from guidelines published by the Pediatric Emergency Care Applied Research Network (PECARN) that included specific clinical criteria for identifying children at low risk.1 Study participants were patients ≤21 years old seen in the ED at CHOP between 2012 and 2016 with TBI (identified using ICD-9 and ICD-10 codes) with a Glasgow Coma Scale score of 13–15 who were discharged home following evaluation. Data abstracted on these children included demographics, time of day, provider type (general pediatrician, pediatrician emergency physician, or nurse practitioner), whether a CT was obtained, and Emergency Severity Index (ESI) score. ESI scores range from 1–5, with 1 being the most acute. The medical records of a random sample of 10% of patients on whom a CT was obtained were reviewed to assess the reason for obtaining the scan and to classify the child’s risk for intracranial injury based on PECARN criteria. The primary outcome was change in rate of CT utilization during the study period, assessed using Wilcoxon rank sum test for trend. Secondary outcomes included rate of ordering CT scans by provider type, using logistic regression and adjusting for ESI scores.Data were analyzed on 21,129 patients with a mean age of 6.6 years; 62% were male. Overall, CT scans were obtained on 6.3% (95% CI, 5.9%, 6.6%) of these patients. During the study period the rate of CT scan utilization fell from 8.3% in 2012 to 4.9% in 2016 (average decrease 0.9% per year; P <0.001 for trend). After adjusting for ESI score, general pediatricians were more likely to obtain a CT scan than pediatric emergency physicians (OR, 1.37; 95% CI, 1.02, 1.83); there was no difference in likelihood of ordering a CT between nurse practitioners and pediatric emergency physicians (OR, 0.63; 95% CI, 0.33, 1.17). In the 10% random sample of patients on whom CT scans were obtained, 30% met PECARN criteria for being low risk. The most common indications for ordering a CT in children <2 years old were concern for non-accidental trauma and vomiting, while for older patients the most common reasons were parental preference and presence of a scalp hematoma.The authors conclude the rate of CT scan ordering in children with mild TBI decreased after implementation of guidelines designed to reduce unnecessary neuroimaging.Dr Bechtel has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Clinical pathways (CPWs) are tools to promote evidence-based healthcare delivery and strive to standardize care for a specific clinical problem in a specific population.2 Thus, compliance with a CPW by a diverse swath of healthcare providers is ultimately the best indicator of its relevance and utility. The primary objective of the current well-done study was to assess the pattern of change in CT utilization in discharged children with mild TBI following the implementation of a CPW in a children’s ED.The authors found that for 5 years, the rate of obtaining CT in children discharged with minor TBI declined by 0.9% per year, a statistically significant decrease, without an accompanying increase of LOS in the ED. However, despite these guidelines, 30% of surveyed Electronic Health Records (EHRs) of discharged children were characterized as low risk by the guidelines and still had a CT obtained. When documented in the EHR, the most common indications for obtaining a CT in this population were age specific. For example, in children younger than 2 years, providers were more concerned about the presence of abusive trauma and vomiting, whereas, in children older than 2 years, parental preference and scalp hematomas drove CT utilization. It may be noted that updated PECARN guidelines do not use vomiting as a risk factor, while parental preference is still a consideration in choosing CT over observation.3 The other interesting finding was that general pediatricians were more likely to order a CT compared with emergency medicine providers. Thus, the dissemination of this CPW to general pediatricians would be helpful to reduce CT use further. (See AAP Grand Rounds. 2017;37[6]:68.)4A CPW for the management of minor closed head trauma in children can lead to the reduction in the utilization of head CTs in childrenAbove and beyond decreasing unnecessary use of expensive resources and decreasing length of ED stay, decreased cranial CT frequency in children with minor TBI reduces exposure to potentially harmful ionizing radiation.4

Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome

Background: Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden. Methods: Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests. Results: SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS &gt; 6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy. Conclusions: Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.

Concordance of Preprocedure Testing With Time-of-Surgery Testing for SARS-CoV-2 in Children.

* Abbreviations: CHOP — : Children’s Hospital of Philadelphia COVID-19 — : coronavirus disease 2019 RT-PCR — : reverse transcriptase polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Surgery in patients with coronavirus disease 2019 (COVID-19) is associated with increased mortality and complications.1 Procedures may generate aerosols or require endotracheal intubation, increasing risk of occupational exposure of health care workers. As medical centers navigate aerosol-generating procedures, preprocedure testing is important for patient and provider safety. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immediately before the procedure would yield the most accurate results. However, scheduling logistics and inadequate turnaround times often necessitate preprocedure testing several days in advance. Thus, patients may have negative preprocedure testing results, yet have active viral replication at the time of surgery. Although patients are instructed to monitor for symptoms after testing, symptom reporting is likely to be insensitive in children because most have mild or no … Address correspondence to Audrey R. Odom John, MD, PhD, 907C ARC/Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318. E-mail: johna3{at}email.chop.edu

Assessing Regional Ventilatory Function in Thoracic Insufficiency Syndrome Patients via Dynamic MRI

Background: Free tidal breathing dynamic MRI (dMRI) is useful for practical clinical application in patients with thoracic insufficiency syndrome (TIS). Methods: Volumetric parameters were derived via 129 dMRI images from 51 normal children and 39 TIS patients for left and right lungs, hemi-diaphragms, and hemi-chest walls during tidal breathing. Pairwise t-testing was performed to compare the parameters from TIS patients before and after surgery. Mahalanobis distances (MDs) utilizing parameters of TIS patients and age-matched normal children were assessed to evaluate the closeness of patient lung function to normality. Linear regression was performed to serve as a reference to estimate volume deviations from normality in TIS patients. Findings: Average MDs for right hemi-diaphragm tidal volume (RDtv) were -1.32+1.04 and -0.05+1.11 pre-operatively and post-operatively, respectively, (p=0.004). Average MDs for the ratio of bilateral hemi-diaphragm tidal volume to bilateral lung tidal volume (BDtv/BLtv) were -1.68+1.21 and -0.04+1.10 pre-operatively and post-operatively, respectively (p = 0.001). MDs decreased after treatment suggesting decreased deviations from normality. Regression results showed that all volumes and tidal volumes significantly increased after treatment (p < 0.001), and that increases were greater than those expected from normal growth for RDtv, RLtv, BDtv, and BLtv. Interpretation: Post-operative tidal volumes of bilateral lungs and bilateral hemi-diaphragms of TIS patients came closer to those of normal children indicating positive treatment effects from surgery. QdMRI facilitates assessment of regional effects of surgery to treat TIS. Funding Statement: This research is supported by a grant 1R01HL150147-01 from the National Institutes of Health. This research is also supported in part by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania through a grant by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001878. Declaration of Interests: There is no conflict of interest or industry support. Ethics Approval Statement: All normal children’s data were acquired under an ongoing prospective research study protocol and all TIS patient data were retrieved from a retrospective study protocol. Both protocols were approved by the Institutional Review Board at the Children’s Hospital of Philadelphia (CHOP) and University of Pennsylvania, along with Health Insurance Portability and Accountability Act waiver.

91. Development of an Electronic Algorithm to Identify Inappropriate Antibiotic Prescribing for Pediatric Otitis Media

BackgroundAntibiotic stewardship (AS) interventions have primarily focused on acute care settings. The majority of antibiotic use, however, occurs in outpatients. The electronic health record (EHR) might provide an effective and efficient tool for outpatient AS. We aimed to develop and validate an electronic algorithm to identify inappropriate antibiotic use for pediatric outpatients with acute otitis media (AOM).MethodsWithin the Children’s Hospital of Philadelphia (CHOP) Care Network, we used ICD-10 diagnostic codes to identify patient encounters for AOM at any CHOP practice between 3/15/17 – 3/14/18. Exclusion criteria included underlying immunocompromising condition, comorbidities, and concurrent infections that might influence antibiotic use. We randomly selected 450 eligible subjects (150 each from academic practices, non-academic practices, and urgent care). Inappropriate antibiotic use based on CHOP and professional society guidelines were assessed via chart review and served as the basis for assessment of the electronic algorithm which was constructed using only data in the electronic health record (EHR). Criteria for appropriateness focused on the decision to prescribe, the choice of antibiotic, and duration of therapy.ResultsOf 450 subjects, median age was 2, 46% were female, and 88% were evaluated by a physician (vs. advanced practice provider). On chart review, the prescribing decision was correct in 438 (97%), of which 25 appropriately received no antibiotics. Of the 413 subjects who were appropriately prescribed an antibiotic, the choice of antibiotic was appropriate in 37 (9%). Finally, of the 413 patients who were appropriately treated, 412 (99.7%) received the correct duration. Test characteristics of the EHR algorithm (compared to chart review) are noted in the Table.ConclusionFor children with AOM, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. This algorithm can also highlight for which elements of prescribing the impact of an intervention might be greatest (i.e., choice of agent). Future work should validate this approach in other health systems and geographic regions and evaluate the impact of an audit and feedback intervention based on this tool.Table. Test Characteristics of Electronic Algorithm for Inappropriate Prescribing, Agent, and Duration Disclosures All Authors: No reported disclosures

151. An Electronic Algorithm to Better Target Antimicrobial Stewardship Program (ASP) Efforts for Children Hospitalized with Community-Acquired Pneumonia (CAP)

BackgroundPediatric antibiotic stewardship programs (ASPs) have been successful in decreasing inappropriate antibiotic use. However, they require considerable time and effort. Approaches to increase ASP efficiency are urgently needed. We developed and validated an electronic algorithm to identify inappropriate antibiotic use in children hospitalized with community-acquired pneumonia (CAP).MethodsAt Children’s Hospital of Philadelphia (CHOP), we used ICD-10 diagnostic codes to identify inpatient patient encounters for pneumonia between 3/15/17 – 3/14/18 for which patients received a systemic antibiotic in the first 48 hours of hospitalization. Exclusion criteria included transfer from another facility, intensive care unit admission or death in first 48 hours, immunocompromising condition, or specific comorbidities. We randomly selected 150 subjects. Inappropriate antibiotic use based on chart review served as the basis for assessment of the electronic algorithm which was constructed using only data in the electronic health record (EHR). Criteria for appropriate prescribing, choice of antibiotic, and duration of therapy were based on established CHOP and IDSA/PIDS guidelines.ResultsOf 148 eligible subjects, median age was 3.8, 48% were female, and 129 (86%) were admitted to a general pediatrics service. On chart review, 147 (99%) subjects were correctly diagnosed with CAP. Of these subjects, the choice of initial antibiotic(s) was appropriate in 133 (90%). Of the 147 subjects, 137 (93%) had an appropriate duration of therapy. Test characteristics of the EHR algorithm (compared to chart review) are noted in the Table.ConclusionIn pediatric patients hospitalized with CAP, the electronic algorithm for identifying inappropriate prescribing, antibiotic choice, and duration was highly accurate. This algorithm could have considerable utility in targeting ASP initiatives. The impact of interventions based on this algorithm should be tested in the futureTest Characteristics of Electronic Algorithm for Inappropriate Prescribing, Agent, and Duration Disclosures All Authors: No reported disclosures

Peripheral blood transcriptomic sub-phenotypes of pediatric acute respiratory distress syndrome

BackgroundAcute respiratory distress syndrome (ARDS) is heterogeneous and may be amenable to sub-phenotyping to improve enrichment for trials. We aimed to identify subtypes of pediatric ARDS based on whole blood transcriptomics.MethodsThis was a prospective observational study of children with ARDS at the Children’s Hospital of Philadelphia (CHOP) between January 2018 and June 2019. We collected blood within 24 h of ARDS onset, generated expression profiles, and performed k-means clustering to identify sub-phenotypes. We tested the association between sub-phenotypes and PICU mortality and ventilator-free days at 28 days using multivariable logistic and competing risk regression, respectively.ResultsWe enrolled 106 subjects, of whom 96 had usable samples. We identified three sub-phenotypes, dubbed CHOP ARDS Transcriptomic Subtypes (CATS) 1, 2, and 3. CATS-1 subjects (n = 31) demonstrated persistent hypoxemia, had ten subjects (32%) with immunocompromising conditions, and 32% mortality. CATS-2 subjects (n = 29) had more immunocompromising diagnoses (48%), rapidly resolving hypoxemia, and 24% mortality. CATS-3 subjects (n = 36) had the fewest comorbidities and also had rapidly resolving hypoxemia and 8% mortality. The CATS-3 subtype was associated with lower mortality (OR 0.18, 95% CI 0.04–0.86) and higher probability of extubation (subdistribution HR 2.39, 95% CI 1.32–4.32), relative to CATS-1 after adjustment for confounders.ConclusionsWe identified three sub-phenotypes of pediatric ARDS using whole blood transcriptomics. The sub-phenotypes had divergent clinical characteristics and prognoses. Further studies should validate these findings and investigate mechanisms underlying differences between sub-phenotypes.