Faculty Bibliography

IMPORTANCE/UNASSIGNED:Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. OBJECTIVE/UNASSIGNED:To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. EXPOSURE/UNASSIGNED:Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. RESULTS/UNASSIGNED:Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

BACKGROUND:Current methods to predict height potential are inaccurate. Predicting height by using MRI of the physeal cartilage has shown promise but the applicability of this technique in different imaging setups has not been well-evaluated. PURPOSE:To assess variability in diffusion tensor imaging of the physis and metaphysis (DTI-P/M) of the distal femur between different scanners, imaging parameters, tractography software, and resolution. STUDY TYPE:Prospective. POPULATION/SUBJECTS:Eleven healthy subjects (five males and six females ages 10-16.94). FIELD STRENGTH/SEQUENCE:3 T; DTI single shot echo planar sequences. ASSESSMENT:Physeal DTI tract measurements of the distal femur were compared between different scanners, imaging parameters, tractography settings, interpolation correction, and tractography software. STATISTICAL TESTS:Bland-Altman, Spearman correlation, linear regression, and Shapiro-Wilk tests. Threshold for statistical significance was set at P = 0.05. RESULTS:) did not significantly affect DTI values (bias = 1.4 [LOA -5.7 to 8.4], P = 0.35) but maintained a strong correlation (ρ = 0.82). Gap size (0 mm vs. 0.6 mm) significantly affects tract volume (bias = 1.8 [LOA -5.4 to 1.8]) but maintains a strong correlation (ρ = 0.93). Comparison of tractography algorithms generated significant differences in tract number, length, and volume while maintaining correlation (ρ = 0.86, 0.99, 0.93, respectively). Comparison of interobserver variability between different tractography software also revealed significant differences while maintaining high correlation (ρ = 0.85-0.98). DATA CONCLUSION:DTI of the pediatric physis cartilage shows high reproducibility between different imaging and analytic parameters. EVIDENCE LEVEL:2 TECHNICAL EFFICACY: Stage 1.

Background Commonly used pediatric lower extremity growth standards are based on small, dated data sets. Artificial intelligence (AI) enables creation of updated growth standards. Purpose To train an AI model using standing slot-scanning radiographs in a racially diverse data set of pediatric patients to measure lower extremity length and to compare expected growth curves derived using AI measurements to those of the conventional Anderson-Green method. Materials and Methods This retrospective study included pediatric patients aged 0-21 years who underwent at least two slot-scanning radiographs in routine clinical care between August 2015 and February 2022. A Mask Region-based Convolutional Neural Network was trained to segment the femur and tibia on radiographs and measure total leg, femoral, and tibial length; accuracy was assessed with mean absolute error. AI measurements were used to create quantile polynomial regression femoral and tibial growth curves, which were compared with the growth curves of the Anderson-Green method for coverage based on the central 90% of the estimated growth distribution. Results In total, 1874 examinations in 523 patients (mean age, 12.7 years ± 2.8 [SD]; 349 female patients) were included; 40% of patients self-identified as White and not Hispanic or Latino, and the remaining 60% self-identified as belonging to a different racial or ethnic group. The AI measurement training, validation, and internal test sets included 114, 25, and 64 examinations, respectively. The mean absolute errors of AI measurements of the femur, tibia, and lower extremity in the test data set were 0.25, 0.27, and 0.33 cm, respectively. All 1874 examinations were used to generate growth curves. AI growth curves more accurately represented lower extremity growth in an external test set (n = 154 examinations) than the Anderson-Green method (90% coverage probability: 86.7% [95% CI: 82.9, 90.5] for AI model vs 73.4% [95% CI: 68.4, 78.3] for Anderson-Green method; χ² test, P < .001). Conclusion Lower extremity growth curves derived from AI measurements on standing slot-scanning radiographs from a diverse pediatric data set enabled more accurate prediction of pediatric growth. © RSNA, 2024 Supplemental material is available for this article.

BACKGROUND/UNASSIGNED:Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE/UNASSIGNED:The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS/UNASSIGNED:A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS/UNASSIGNED:This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE/UNASSIGNED:Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Purpose or Case Report: To assess variability in diffusion tensor imaging of the physis and metaphysis (DTI-P/M) of the distal femur between scanners, observers, tractography software, and resolution. Methods & Materials: We prospectively obtained DTI-P/M (20 directions, b values of 0 and 600 sec/mm2) in 11 healthy subjects (5 males, 6 females) ages 10-15 (mean 12.54) and quantified tract volume, tract length, and number of tracts in the distal femoral physis. Each subject was imaged in both GE and Siemens 3T units, and the sequence was performed twice in each session with voxel sizes of 2x2x3mm or 1x1x2mm and gap sizes of 0mm and 0.6 mm (22 studies). We compared interobserver variability (with two observers) using hand-drawn regions of interest in the distal femur physis between two tractography software, Trackvis (FACT algorithm) and DSI Studio (Euler algorithm), both with a 40o angular threshold. For DSI Studio, we set the tracking threshold to 0.1, length range to 0-200mm, and seed termination to 1000000. We compared tract number, length, and volume and fractional anisotropy, between the 22 studies using Spearman's correlation and Bland-Altman (BA) plots.
Result(s): Correlation between Siemens and GE was significant between Siemens with 2x2x3mm voxel size and 0.6mm gap with GE 1x1x2mm voxel size and 0mm gap (rho = 0.93, p<10^- 15). Bland-Altman plots normalizing for voxel size between Siemens and GE showed no bias in inter-scanner variability (bias -5.76, BA limits of agreement (LOA) -24.31 and 12.78), nor was there significant intrascanner variability between consecutive runs of either Siemens (bias 0.565, BA LOA -10.31 and 9.18) or GE (bias 0.309, BA LOA -2.08 and 2.69). The 95% confidence intervals for the inter-scan (Mean=1.109, 95%-CI [- 0.84 3.06]) and intra-scan (Mean=0.3, 95%-CI [-0.31 0.91]) both included zero confirming no significant bias between scanners (p<0.05). Trackvis, the current standard for DTI-P/M, had high interobserver agreement (rho = 0.95) whereas DSI Studio showed poor interobserver agreement (rho = 0.29).
Conclusion(s): DTI-P/M shows high GE and Siemens inter- and intra-scanner reproducibility and low variability. Trackvis has low interobserver variability for tractography generation

BACKGROUND:Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS:Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS:Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS:In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

INTRODUCTION: The pathological manifestations of vascular air embolism (VAE) depend on the volume and rapidity of gas entry, and result from mechanical obstruction, leading to ischemia and inflammatory reactions to air as a foreign body. Physiologic effects on the cardiovascular, neurologic, or pulmonary systems may be trivial or catastrophic.
METHOD(S): A 17-year-old boy with anti-MOG syndrome was admitted for plasmapheresis for optic neuritis. Minutes after removal of his internal jugular central venous catheter (CVC), he developed paresthesias, chest discomfort, and sudden onset cough, progressing to unresponsiveness. Noncontrast head CT was negative for acute intracranial process. Upon transfer to the PICU, the patient decompensated further, requiring intubation and initiation of vasoactives for refractory shock. CT angiogram of the head and neck was unremarkable. Initial brain MRI showed diffuse leptomeningeal enhancement concerning for infection, however extensive infectious workup was negative. Repeat MRI revealed numerous scattered foci of acute and lateacute infarcts consistent with an embolic event. Cardiac workup was significant for an EKG with anterolateral ST elevation, elevated serum troponin, and TEE demonstrating left ventricular hypokinesia and a trivial PFO. Cardiac MRI confirmed an intraventricular septal infarct. The sudden onset of signs of neurologic and cardiopulmonary compromise with temporal relation to CVC manipulation led to the clinical diagnosis of VAE.
RESULT(S): We describe a rare case of CVC-associated VAE in a pediatric patient resulting in neurologic injury and cardiopulmonary collapse. When air enters the vasculature, it can migrate along three major pathways: via pulmonary circulation, paradoxically via intra-cardiac shunt, or to the cerebral venous system via retrograde ascension. In most described cases, emboli migrate along only one or two of these pathways. In this case, the patient developed ARDS, cardiogenic shock, and multiple ischemic strokes, suggesting embolic migration along all three pathways. There is inadequate awareness of VAE as a potentially fatal complication of CVC use. Though a rare complication, the vast majority of catheter-associated VAE are largely preventable with focused instruction and reinforcement through enhanced supervision

OBJECTIVES/OBJECTIVE:Influenza is an environmental pathogen and infection presents as a range from asymptomatic to fulminant illness. Though treatment is supportive, antiviral agents have a role in the management of infection. Pediatric use of peramivir is largely based on reports and extrapolations of pharmacokinetic data. We seek to describe efficacy and safety of peramivir in critically ill pediatric patients. METHODS:This is a retrospective, institutional review board-approved chart review of all patients under 21 years of age, admitted to the PICU, and treated with peramivir for influenza H1N1 infection between January 1, 2016, and March 31, 2016, at a single-center, 12-bed PICU. The primary outcome was time to sustained resolution of fever; secondary outcomes included dose, duration, and adverse effects of peramivir therapy. RESULTS:Seven patients were included with median age of 3.7 years. Median time to sustained resolution of fever was 49.3 hours, median duration of mechanical ventilation was 14.2 days, median ICU LOS was 18.7 days, and hospital LOS was 24.7 days. No patients suffered mortality. Three patients experienced leukopenia, one of which experienced a concurrent neutropenia. Three patients experienced hyperglycemia, 2 experienced hypertension, 1 experienced increased aspartate aminotransferase and increased alanine aminotransferase, and 1 experienced diarrhea. All adverse events assessed were classified as possible using published adverse event causality assessments. CONCLUSIONS:Peramivir has been shown to be an effective therapy for the treatment of influenza H1N1 in critically ill pediatric patients. In our experience with 7 pediatric patients, peramivir was well tolerated at typical durations of therapy; however, increased vigilance is warranted during prolonged courses or in patients with reasons for altered pharmacokinetics and pharmacodynamics.

Aims & Objectives: High frequency percussive ventilation (HFPV) rapidly delivers subphysiologic tidal volumes using a volume-diffusive respirator and provides similar or improved oxygenation and ventilation at lower peak, mean, and end-expiratory pressures when compared with conventional ventilation (CV). We present the case of a child with acute respiratory distress syndrome (ARDS) from pulmonary hemorrhage treated with HFPV. Methods Case Report Results A ventilator-dependent 5-year-old male with pyruvate dehydrogenase deficiency presented with acute hypoxemic respiratory failure. Chest radiography showed bilateral pulmonary infiltrates and tracheal aspirate revealed hemosiderin laden macrophages. Methylprednisolone and empiric antibiotics were administered for pulmonary hemorrhage and severe ARDS. The patient was placed on high-frequency oscillatory ventilation (HFOV) then HFPV (Figure 1). Subsequent dislodgement of a blood clot was followed by improvement in OI and chest radiography (Figure 2). The patient was discharged on home ventilator settings on HD#11. (Figure prsented). Conclusions HFPV has been shown to decrease morbidity and mortality by improving mucociliary clearance. To our knowledge this is the first reported case of HFPV use in a pediatric patient with ARDS from pulmonary hemorrhage. Early implementation of HFPV may be a safe and effective ECMO-sparing strategy to improve oxygenation in patients with ARDS due to pulmonary hemorrhage