Validated anxiety assessments among pediatric patients with peanut allergy on oral immunotherapy.

BACKGROUND: Although efficacy, safety, and quality of life measures associated with peanut oral immunotherapy (OIT) have been studied, the relationship between peanut OIT and clinical anxiety has not yet been evaluated. The latter is important to help providers and families have an improved shared medical decision discussion around the benefits of initiating OIT. OBJECTIVE: To investigate the relationship between undergoing OIT and anxiety in patients with peanut allergy. METHODS: In this prospective cross-sectional cohort study, using validated and age-appropriate anxiety scales administered with electronic survey questionnaires, we used generalized linear regressions to compare anxiety between patients undergoing OIT and similar patients with peanut allergy but not on OIT (controls). RESULTS: In the younger cohort (<7 years, n = 80), there was generally a low prevalence of diagnosable anxiety across patients on OIT and controls. In the older cohort (>7 years, n = 125), there was a higher prevalence of anxiety but no clinically meaningful difference between anxiety scores of patients on OIT and controls. In the older cohort, patients with asthma were more likely to have higher mean anxiety scores (P = .04), as were female patients compared with male patients (P = .004). A subanalysis of separation anxiety scores in the older cohort revealed that younger age (7-12 years vs >12 years, P < .001), non-White race (P = .04), and eczema (P = .02) were found to be meaningful predictors of higher scores. A subanalysis of social anxiety on the older cohort pointed toward non-White race as a meaningful predictor of higher scores (P < .02). CONCLUSION: The clinical implications of these findings suggest that allergists should particularly consider screening children with food allergy for anxiety and anxiety subtypes among patients who are non-White, female, or have asthma.

Parent-reported penicillin allergies in children: A qualitative study.

BACKGROUND: Penicillin allergies are commonly reported in children. Most reported penicillin allergies are false, resulting in the unnecessary selection of alternative antibiotic treatments that promote antibiotic resistance. While formal allergy testing is encouraged to establish a diagnosis of penicillin allergy, children are rarely referred for allergy testing, and study of parents' experiences and perceptions of their child's reported penicillin allergy is limited. We aimed to describe parents' experiences and perceptions of their child's penicillin allergy and attitudes towards penicillin allergy testing to identify opportunities to engage parents in antimicrobial stewardship efforts. METHODS: This was a qualitative descriptive study. RESULTS: Eighteen parents participated in this study. Parents' children were on average 2 years old when the index reaction occurred, and 7 years had passed since the reaction. Transcripts revealed that participants were receptive to penicillin allergy testing for their child after learning the consequences of penicillin allergy and availability of allergy testing. Four major themes emerged from data (1) parents' making sense of allergy; (2) parents' impressions of allergy label, (3) parents' attitudes towards allergy testing, and (4) parents' desire to be informed of testing availability. CONCLUSIONS: Efforts are needed to engage parents in addressing spuriously reported penicillin allergies.

The immunologic response to severe acute respiratory syndrome coronavirus 2.

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated the worst global pandemic in a century, which has caused millions of infections and deaths as well as massive economic repercussions. Objective: As with any pathogenic virus, it is crucial to understand its unique interactions with the human immune system so that pharmaceutical and prophylactic interventions can be deployed to effectively control the pandemic. Methods: A literature search by using PubMed was conducted in 2020 with variants of the terms "COVID-19," "SARS-CoV-2," and "immunological response." English language articles that presented original data about the immunologic response to coronavirus disease 2019 (COVID-19) were selected for review. This article reviewed the current understanding of the innate and adaptive immune responses to SARS-CoV-2 infection, including their relationship to current therapeutic and diagnostic strategies. Results: SARS-CoV-2 uses several unique molecular techniques to evade detection by the innate immune system early in the course of infection, and upregulation of these innate immune pathways may possibly accelerate the time to recovery and prevent severe disease. Although the majority of cases results in the patients' recovery, a significant proportion of infections result in deaths prompted by the host's inflammatory overreaction to the infection, a response that can be attenuated with corticosteroids and potentially other immune modulators. Conclusion: Current work by the scientific community to further understand how SARS-CoV-2 interacts with the human immune system will be invaluable to our response and preparedness for future coronavirus pandemics.

Cytokine profiles in severe SARS-CoV-2 infection requiring extracorporeal membrane oxygenation support.

It has been postulated that the underlying pathophysiology of COVID-19 is mediated by cytokine storm resulting in a hyperinflammatory state. A similar kind of cytokine-storm has been described in individuals undergoing veno-venous extracorporeal membrane oxygenation (VV ECMO) support. There is therefore concern that initiation of VV ECMO support among COVID19 patients could further exacerbate this dysregulated inflammatory response. In this prospective cohort study, we describe the clinical course and cytokine fluctuations in eight subjects treated with VV ECMO for management of refractory respiratory failure from COVID19. Among all eight patients, cytokine elevations were noted among Interleukin 6 (IL-6), Interleukin 10 (IL-10), and Interleukin 2 Receptor (CD25) soluble (sIL2R). Although further research is necessary, among our cohort of patients it did not appear that initiation of VV ECMO worsened cytokine storm.

Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19.

We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.

A retrospective matched cohort single-center study evaluating outcomes of COVID-19 and the impact of immunomodulation on COVID-19-related cytokine release syndrome in solid organ transplant recipients.

This retrospective matched cohort study describes 30 solid organ transplant (SOT) patients with Coronavirus Disease 2019 (COVID-19) matched 1:2 to 60 non-SOT patients (control group) based on age, body mass index (BMI), and comorbidities (hypertension and diabetes mellitus with hemoglobin A1c > 8.0%). The SOT group had a higher proportion of cardiovascular disease (P < .05). During the index hospitalization, there were no significant differences with regard to disease severity or critical care needs (mechanical intubation, vasopressors, and renal replacement therapy). At 28 days, 4 (13%) patients died in the SOT group and 8 (13%) patients died in the control group (P = 1.0). Nineteen patients received tocilizumab in the SOT group compared to 29 patients in the control group. Among these patients, interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL2R) levels increased after tocilizumab and interleukin-10 (IL-10) levels decreased after tocilizumab. Overall, SOT patients had comparable mortality to non-SOT patients, although numerically more SOT patients received tocilizumab (63% vs 48%) and steroids (37% vs 20%). Larger, multi-center studies are needed to ascertain these findings. Lastly, the complex cytokine release syndrome in COVID-19 remains an area of intense research and the analysis of key interleukin levels (IL-6, IL-10, and sIL2R) in this study contributes to the understanding of this process.

Successful Management of Eosinophilic Esophagitis Using Traditional Chinese Medicine: A Case Report.

Eosinophilic Esophagitis (EoE) is a relatively recently described condition, with rapidly increasing prevalence over the past several years. There is unfortunately no cure for EoE, and treatment involves food elimination and off-label use of topical steroids. These treatments can have significant impacts on quality of life for patients. Traditional Chinese Medicine (TCM) has been shown to decrease Th2 cytokines which are implicated in the pathophysiology of EoE. We present an 11-year-old male with severe EoE who was treated with TCM and able to achieve complete remission. Further modalities of treatment for EoE should continue to be pursued.

Repurposing antimicrobial stewardship tools in the electronic medical record for the management of COVID-19 patients.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.

Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019: Survival and Clinical Outcomes.

BACKGROUND: Tocilizumab, an IL-6 receptor antagonist, can be used to treat cytokine release syndrome (CRS), with observed improvements in a coronavirus disease 2019 (COVID-19) case series. RESEARCH QUESTION: The goal of this study was to determine if tocilizumab benefits patients hospitalized with COVID-19. STUDY DESIGN AND METHODS: This observational study of consecutive COVID-19 patients hospitalized between March 10, 2020, and March 31, 2020, and followed up through April 21, 2020, was conducted by chart review. Patients were treated with tocilizumab using an algorithm that targeted CRS. Survival and mechanical ventilation (MV) outcomes were reported for 14 days and stratified according to disease severity designated at admission (severe, ≥ 3 L supplemental oxygen to maintain oxygen saturation > 93%). For tocilizumab-treated patients, pre/post analyses of clinical response, biomarkers, and safety outcomes were assessed. Post hoc survival analyses were conducted for race/ethnicity. RESULTS: Among the 239 patients, median age was 64 years; 36% and 19% were black and Hispanic, respectively. Hospital census increased exponentially, yet MV census did not. Severe disease was associated with lower survival (78% vs 93%; P < .001), greater proportion requiring MV (44% vs 5%; P < .001), and longer median MV days (5.5 vs 1.0; P = .003). Tocilizumab-treated patients (n = 153 [64%]) comprised 90% of those with severe disease; 44% of patients with nonsevere disease received tocilizumab for evolving CRS. Tocilizumab-treated patients with severe disease had higher admission levels of high-sensitivity C-reactive protein (120 vs 71 mg/L; P < .001) and received tocilizumab sooner (2 vs 3 days; P < .001), but their survival was similar to that of patients with nonsevere disease (83% vs 91%; P = .11). For tocilizumab-treated patients requiring MV, survival was 75% (95% CI, 64-89). Following tocilizumab treatment, few adverse events occurred, and oxygenation and inflammatory biomarkers (eg, high-sensitivity C-reactive protein, IL-6) improved; however, D-dimer and soluble IL-2 receptor (also termed CD25) levels increased significantly. Survival in black and Hispanic patients, after controlling for age, was significantly higher than in white patients (log-rank test, P = .002). INTERPRETATION: A treatment algorithm that included tocilizumab to target CRS may influence MV and survival outcomes. In tocilizumab-treated patients, oxygenation and inflammatory biomarkers improved, with higher than expected survival. Randomized trials must confirm these findings.