Background Multisystem inflammatory syndrome in children (MIS-C) is a febrile syndrome that is observed in the pediatric population following severe acute respiratory syndrome 2 (SARS-CoV-2) infection. Vaccines have prevented or lessened the severity of the initial acute respiratory infection, while their effectiveness against severe MIS-C is just beginning to be reported. Case presentation Here we report a fully vaccinated teenage female with no known history of SARS-CoV-2 infection who presented with shock and heart failure. Her presentation was initially thought secondary to a retropharyngeal abscess but was later identified as MIS-C after confirmed nucleocapsid antibody. Conclusions Given the recent Omicron waves, the ongoing international outbreaks with evolving variants and the continued evolution of the COVID-19 pandemic, this case emphasizes the need to include MIS-C in the differential diagnosis, even in a fully vaccinated, previously healthy child.

Background Asparaginase is a key component of pediatric therapy for Acute lymphoblastic leukemia (ALL). Two formulations available in the USA are pegylated E. coli asparaginase (PEG) and Erwinia chrysanthemi asparaginase (Erwinaze). Hypersensitivity reactions have been observed in ~ 20% of patients receiving PEG. Patients with overt symptoms of hypersensitivity are typically switched to Erwinaze. In cases of hypersensitivity, anti-asparaginase antibodies may be present that neutralize circulating asparaginase and in some cases may present without clinical signs, a phenomenon known as silent inactivation. Few studies have prospectively evaluated the incidence of silent inactivation in pediatric ALL patients. In this prospective study, we performed therapeutic drug monitoring of asparaginase levels on newly diagnosed pediatric ALL patients to determine the incidence of silent inactivation and to switch patients to Erwinaze, if silent inactivation was detected. Methods A prospective study was conducted at CHOC Children's Hospital on patients with newly diagnosed ALL or lymphoblastic lymphoma between 2016 to 2018. Patients designated as high or very high risk B-ALL post induction, T-ALL and B/T lymphoblastic lymphoma were enrolled. Patients received therapy on or according to a COG protocol with PEG (2500 IU/m2) administered via 2-hour i.v. infusion without antihistamine or steroid premedication. Asparaginase activity was measured days 7 and 14 after each of the two PEG doses during Consolidation. Serum asparaginase level of >0.1 IU/ml and >0.02 IU/ml was considered therapeutic at 7 or 14 days post PEG, respectively. Silent inactivation was defined as serum asparaginase levels below these values without signs of overt allergy. Any patient found to have silent inactivation was immediately switched to Erwinaze. Patient characteristics, common adverse events associated with asparaginase and serum asparaginase levels were analyzed. Descriptive statistics and Pearson's coefficient was used for analysis. Results Thirty-nine patients were enrolled with a mean age of 9.8 years (range, 1-23) with the majority being B-ALL (87.2%) of which 3 were Ph-like (Table 1). Twelve patients (30.7%) had overt hypersensitivity and one patient (2.6%) had silent inactivation. One patient had overt hypersensitivity after completion of the PEG infusion with a measured asparaginase level 7 days post that was therapeutic. One-hundred fifteen drug levels were collected, for an average of 2.9 levels per patient (maximum 4 levels). There was a difference in mean asparaginase activity in patients without hypersensitivity compared to those with hypersensitivity (1.110 IU/mL versus 0.737 IU/mL, respectively, p=.0095). There were no significant differences in asparaginase levels based on age, gender or BSA. The highest asparaginase level observed was 7 days post the 2nd dose of asparaginase in Consolidation. Overall, the incidence of patients with CTCAE grade ≥2 transaminitis was 51.3% (n=20), hyperglycemia 2.6 % (n=1), hyperbilirubinemia 5.1% (n=2), and thrombosis 2.6% (n=1). Pancreatitis of any grade was not observed in this cohort. Discussion We detected silent inactivation in a single patient who had an asparaginase level of 0.01 seven days after the first dose of PEG and showed no signs of overt allergic reaction. This patient was switched to Erwinaze and an asparaginase level drawn 48 hours post Erwinaze was therapeutic at 0.719. Another patient developed a hypersensitivity reaction 12-hours after PEG and had a serum asparaginase level of 1.29 7-days post PEG. This suggests that not all anti-asparaginase antibodies are neutralizing since this patient continued to demonstrate therapeutic drug levels. The incidence of allergic reactions to PEG at our institution appears higher than reported in prior studies. Our data shows a statistically significant difference between serum asparaginase levels in patients with and without hypersensitivity. Our study also shows that silent inactivation exists in a very small proportion of patients. Additionally, patients who develop late allergic reactions to PEG may still have therapeutic asparaginase levels. Thus, monitoring of asparaginase levels may be warranted to detect silent inactivation and to monitor asparaginase levels in patients who develop delayed hypersensitivity. A larger prospective study is needed to confirm these results. Disclosures No relevant conflicts of interest to declare.

Background Multisystem inflammatory syndrome in children (MIS-C) is a febrile syndrome that is observed in the pediatric population following severe acute respiratory syndrome 2 (SARS-CoV-2) infection. Vaccines have prevented or lessened the severity of the initial acute respiratory infection, while their effectiveness against severe MIS-C is just beginning to be reported. Case presentation Here we report a fully vaccinated teenage female with no known history of SARS-CoV-2 infection who presented with shock and heart failure. Her presentation was initially thought secondary to a retropharyngeal abscess but was later identified as MIS-C after confirmed nucleocapsid antibody. Conclusions Given the recent Omicron wave, the ongoing international outbreaks with the BA.2 subvariant and the continued evolution of the COVID-19 pandemic, this case emphasizes the need to include MIS-C in the differential diagnosis, even in a fully vaccinated, previously healthy child.

INTRODUCTION: As endovascular treatment options for acute ischemic stroke evolve, it is important to study the conditions and decisions that lead to successful outcomes so that future interventions may be better tailored for each individual. Bayesian networks provide a method for studying the conditional dependencies between variables and have been applied in other areas of medicine. In this work, we present a Bayesian network of acute ischemic stroke for analyzing the dependencies between a patient’s clinical and imaging presentation, therapeutic interventions, and outcomes. METHODS: 790 unique episodes of acute ischemic stroke from the last five years (2006-2012) were retrieved from our institution’s quality improvement repository. A subset of variables from each case was extracted and modeled in a Bayesian network. Variable selection and connectivity was guided by a review of current practice guidelines and the domain knowledge of clinical investigators. Conditional probabilities between variables were then calculated using expectation maximization. RESULTS: The Bayesian network may be manipulated through a graphical user interface to investigate the likelihood of different clinical scenarios. For example, evidence regarding patient presentation may be set and then combinations of interventions may be applied to observe possible outcomes. Additionally, the model accommodates the integration of utility nodes to support exploration of a patient’s projected quality-adjusted life expectancy (QALE) as a function of their clinical state and variable treatment decisions. CONCLUSION: The presented model supports a pertinent set of variables and provides an initial tool for clinicians and researchers to study how combinations of patient evidence and interventions affect outcomes in acute stroke. This information may be useful for suggesting subsequent investigations on methods for improving existing treatment protocols.

Introduction: Fever and neutropenia (FN) is a major side effect of chemotherapy in pediatric oncology patients and can result in hospitalization, morbidity, or mortality. Cancer patients are at increased risk for bacteremia due to immunosuppression and their central venous catheters (CVC). Guidelines for the management of FN exist and inpatient admission with empiric parenteral antibiotics for high risk children with severe neutropenia (Absolute Neutrophil Count (ANC) ≤ 500/µl) is often the standard of care. However, the management of mildly neutropenic or non-neutropenic patients is variable across institutions. The goal of this single-institution study is to assess the safety and efficacy of our algorithm for the outpatient management of FN in "Low Risk" designated oncology patients with a CVC at CHOC Children's Hospital. Methods: Febrile oncology patients with a CVC are managed according to our "Low Risk" Outpatient Care Guidelines based on the following criteria: patients are well appearing and outpatient at the time of initial fever, have an ANC >500, do not have any "High Risk" features or allergy to cephalosporin. "Low Risk" patients with fever have their blood culture drawn from their central line and intravenous (IV) Ceftriaxone is administered with the initial dose in the outpatient setting. The patients subsequently return the next day for follow-up and the second dose of Ceftriaxone. If their fever persists to the 3rd day or if the blood culture is positive, the patient is admitted for inpatient parenteral antibiotics. A retrospective review of medical records was performed for patients treated according to these criteria who presented to the outpatient setting with fever from April 2014-March 2016. Results: In the two year time period, 96 febrile episodes in 68 patients were treated according to our "Low Risk" Outpatient Care Guidelines (Table 1). The average age, temperature, and ANC was 7.2 years, 101.2 degrees, and 4443.1/µl, respectively. Eighty-five (88.5%) patients had leukemia, the most common being B-ALL in 77 patients. The majority had portacaths, while four episodes had broviacs. Sixty of 96 encounters (62.5%) presented with fever without an identifiable source. Only three of 96 episodes had bacteremia (3.1%). Isolated organisms from these 3 patients' CVC include Streptococcus thoraltensis and Staphylococcus epidermidis. These 3 patients, as per the Care Guidelines, were admitted inpatient for parenteral antibiotics due to their positive blood culture. Seventy patient episodes (72.9%) were treated successfully with outpatient Ceftriaxone with subsequent resolution of their fever and negative blood cultures. Twenty-three encounters that were safely treated in the outpatient setting had an identifiable infectious source, and 22 of those (95.7%) were upper respiratory infections (URI's) or pneumonias. Twenty-six of the 96 encounters (27.1%) resulted in admission. The majority of the admissions were due to fevers that persisted >3 days. Of the 26 encounters admitted, 13 (50%) had an identifiable source of infection such as a URI, infectious diarrhea, urinary tract infection (UTI), or bacteremia (in 3 patients). Discussion: This study demonstrates that our institution's outpatient management guideline for FN in "Low Risk" designated oncology patients with an indwelling catheter is safe and feasible. Seventy encounters out of 96 did not require hospital admission and were sent home safely from the outpatient setting for follow-up the next day. Of the three encounters who had a positive blood culture, all were age 6 or younger, 2 were male, and 1 had a broviac. All three of these encounters were not neutropenic (ANC 4099-6900) and presented with no unusual symptoms. This underlines the importance of prompt blood cultures and antibiotic administration in all patients with fever in our diagnostic evaluation. While 27.1% of the febrile encounters resulted in admission, all were safely admitted within three days, per protocol, due to persistent fever. Our study shows that outpatient management of a subset of patients who fit the "Low Risk" criteria is safe, feasible and effective. There are many benefits of outpatient management of FN. Patient and family quality of life is higher, hospital costs are lower, and hospital-acquired infections decrease. Our next study will prospectively analyze whether oral antibiotics are a safe and effective option in this subset of patients. Disclosures No relevant conflicts of interest to declare.