Faculty Bibliography

BACKGROUND:Distal femoral diffusion tensor imaging (DTI) is a predictor of height gain but it is uncertain whether DTI can demonstrate differences in growth potential between the tibia and femur. OBJECTIVE:To explore the differences in structure and growth potential of the proximal tibia physeal-metaphyseal complex compared to those of the distal femur through DTI tractographic characterization and DTI metric comparison. MATERIALS AND METHODS/METHODS:. Tract parameters including number, length, volume, and fractional anisotropy were measured. Regression analysis with linear and negative binomial models, incorporating bone age-based quadratic fitting, characterized DTI parameter changes in relation to bone age and sex, as well as variations between physes. Femorotibial ratios were calculated based on paired DTI parameter absolute values during peak height gain. The study was approved by the institutional review board of two tertiary pediatric centers in compliance with the Health Insurance Portability and Accountability Act. RESULTS:Proximal tibial tracts were more numerous in the central physis, whereas distal femoral tracts predominated peripherally. Tract volume rose and fell during adolescence and peaked earlier in females (140-160 months vs. 160-180 months, P=0.02). At maximal height velocity (160 months), tibial tract volume (5.43 cc) was 37.4% of total knee tract volume (14.53 cc). Tibial fractional anisotropy decreased and then increased, both earlier than the femur. CONCLUSION/CONCLUSIONS:Proximal tibial and distal femoral tract distributions differ. The tibia accounts for 37.4% of total knee tract volume during maximal height velocity. Tract volumes rise and fall, earlier in females. Tibiofemoral ratios of DTI metrics resemble known ratios of growth rates between tibia and femur.

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/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.

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

OBJECTIVES: To report our experience with the use of IV enoxaparin in neonatal and pediatric patients in the ICU. DESIGN: We performed a case control from January 1, 2009, to June 30, 2012, comparing patients that received IV enoxaparin to controls that received subcutaneous enoxaparin. Cases were matched to controls in a 1:2 manner. IV enoxaparin doses were infused over 30 minutes and anti-Factor Xa levels were drawn 4 hours after the start of the IV infusion or 4 hours after a subcutaneous dose. SETTING: The pediatric and cardiac ICUs of a tertiary/quaternary, free-standing, academic children's hospital. PATIENTS: Forty-five neonatal and pediatric patients receiving prophylactic or therapeutic enoxaparin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifteen cases and 30 controls were included. Of 15 patients, 13 received IV enoxaparin for treatment and two received IV enoxaparin for prophylaxis as compared with 25 of 30 controls receiving subcutaneous enoxaparin for treatment and five receiving subcutaneous enoxaparin for prophylaxis. The ages for the cases ranged from 21 days to 16 years with a median weight of 5 kg, and the ages for controls ranged from 10 days to 23 years with a median weight of 31 kg. The median duration of IV therapy was 11 days (range, 1-120 d) and the median duration for subcutaneous therapy was 15 days (range, 3-85 d). The mean initial IV dose was 1.14 +/- 0.38 mg/kg/dose q12h, and the mean initial subcutaneous dose was 0.85 +/- 0.2 mg/kg/dose subcutaneous q12h (p = 0.003). The mean therapeutic IV dose was 1.31 +/- 0.52 mg/kg/dose q12h, and the mean therapeutic subcutaneous dose was 0.9 +/- 0.3 mg/kg/dose q12h (p = 0.016). There were no adverse events reported related to bleeding, thrombosis, or hypersensitivity in any of the cases or controls evaluated. CONCLUSION: The pharmacodynamics of a 30-minute IV enoxaparin infusion was found to produce therapeutic 4 hour anti-Factor Xa levels similar to subcutaneous doses. Although this was a small study, there were no adverse events, suggesting the safety profile of IV enoxaparin may be similar to subcutaneous dosing with the added benefit of less pain associated with IV dosing. These findings suggest that IV enoxaparin may be a viable option for anticoagulating critically ill children and its use warrants further study.