Doymaz, Sule
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Publication Open Access Investigating Health Disparities Associated With Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Infection.(2022-09-07) Zambrano, Laura D; Ly, Kathleen N; Link-Gelles, Ruth; Newhams, Margaret M; Akande, Manzilat; Wu, Michael J; Feldstein, Leora R; Tarquinio, Keiko M; Sahni, Leila C; Riggs, Becky J; Singh, Aalok R; Fitzgerald, Julie C; Schuster, Jennifer E; Giuliano, John S; Englund, Janet A; Hume, Janet R; Hall, Mark W; Osborne, Christina M; Doymaz, Sule; Rowan, Courtney M; Babbitt, Christopher J; Clouser, Katharine N; Horwitz, Steven M; Chou, Janet; Patel, Manish M; Hobbs, Charlotte; Randolph, Adrienne G; Campbell, Angela PBackground: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities. Methods: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls aged less than 18 years frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression. Results: We compared 241 MIS-C cases to 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28). Conclusions: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.Publication Open Access Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.Feldstein, Leora R; Tenforde, Mark W; Friedman, Kevin G; Newhams, Margaret; Rose, Erica Billig; Dapul, Heda; Soma, Vijaya L; Maddux, Aline B; Mourani, Peter M; Bowens, Cindy; Maamari, Mia; Hall, Mark W; Riggs, Becky J; Giuliano, John S; Singh, Aalok R; Li, Simon; Kong, Michele; Schuster, Jennifer E; McLaughlin, Gwenn E; Schwartz, Stephanie P; Walker, Tracie C; Loftis, Laura L; Hobbs, Charlotte V; Halasa, Natasha B; Doymaz, Sule; Babbitt, Christopher J; Hume, Janet R; Gertz, Shira J; Irby, Katherine; Clouser, Katharine N; Cvijanovich, Natalie Z; Bradford, Tamara T; Smith, Lincoln S; Heidemann, Sabrina M; Zackai, Sheemon P; Wellnitz, Kari; Nofziger, Ryan A; Horwitz, Steven M; Carroll, Ryan W; Rowan, Courtney M; Tarquinio, Keiko M; Mack, Elizabeth H; Fitzgerald, Julie C; Coates, Bria M; Jackson, Ashley M; Young, Cameron C; Son, Mary Beth F; Patel, Manish M; Newburger, Jane W; Randolph, Adrienne GImportance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, design, and participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure: SARS-CoV-2. Main outcomes and measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.Publication Open Access Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.LaRovere, Kerri L; Riggs, Becky J; Poussaint, Tina Y; Young, Cameron C; Newhams, Margaret M; Maamari, Mia; Walker, Tracie C; Singh, Aalok R; Dapul, Heda; Hobbs, Charlotte V; McLaughlin, Gwenn E; Son, Mary Beth F; Maddux, Aline B; Clouser, Katharine N; Rowan, Courtney M; McGuire, John K; Fitzgerald, Julie C; Gertz, Shira J; Shein, Steven L; Munoz, Alvaro Coronado; Thomas, Neal J; Irby, Katherine; Levy, Emily R; Staat, Mary A; Tenforde, Mark W; Feldstein, Leora R; Halasa, Natasha B; Giuliano, John S; Hall, Mark W; Kong, Michele; Carroll, Christopher L; Schuster, Jennifer E; Doymaz, Sule; Loftis, Laura L; Tarquinio, Keiko M; Babbitt, Christopher J; Nofziger, Ryan A; Kleinman, Lawrence C; Keenaghan, Michael A; Cvijanovich, Natalie Z; Spinella, Philip C; Hume, Janet R; Wellnitz, Kari; Mack, Elizabeth H; Michelson, Kelly N; Flori, Heidi R; Patel, Manish M; Randolph, Adrienne GImportance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, design, and participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures: Severe acute respiratory syndrome coronavirus 2. Main outcomes and measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.Publication Open Access Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.(2021-06-16) Son, Mary Beth F; Murray, Nancy; Friedman, Kevin; Young, Cameron C; Newhams, Margaret M; Feldstein, Leora R; Loftis, Laura L; Tarquinio, Keiko M; Singh, Aalok R; Heidemann, Sabrina M; Soma, Vijaya L; Riggs, Becky J; Fitzgerald, Julie C; Kong, Michele; Doymaz, Sule; Giuliano, John S; Keenaghan, Michael A; Hume, Janet R; Hobbs, Charlotte V; Schuster, Jennifer E; Clouser, Katharine N; Hall, Mark W; Smith, Lincoln S; Horwitz, Steven M; Schwartz, Stephanie P; Irby, Katherine; Bradford, Tamara T; Maddux, Aline B; Babbitt, Christopher J; Rowan, Courtney M; McLaughlin, Gwenn E; Yager, Phoebe H; Maamari, Mia; Mack, Elizabeth H; Carroll, Christopher L; Montgomery, Vicki L; Halasa, Natasha B; Cvijanovich, Natalie Z; Coates, Bria M; Rose, Charles E; Newburger, Jane W; Patel, Manish M; Randolph, Adrienne GBackground: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. Methods: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. Results: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. Conclusions: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).Publication Open Access Clinical Manifestations and Outcomes of Critically Ill Children and Adolescents with Coronavirus Disease 2019 in New York City.(2020-07-16) Derespina, Kim R; Kaushik, Shubhi; Plichta, Anna; Conway, Edward E; Bercow, Asher; Choi, Jaeun; Eisenberg, Ruth; Gillen, Jennifer; Sen, Anita I; Hennigan, Claire M; Zerihun, Lillian M; Doymaz, Sule; Keenaghan, Michael A; Jarrin, Stephanie; Oulds, Franscene; Gupta, Manoj; Pierre, Louisdon; Grageda, Melissa; Ushay, H Michael; Nadkarni, Vinay M; Agus, Michael S D; Medar, Shivanand SObjectives: To describe the clinical manifestations and outcomes of critically ill children with coronavirus disease-19 (COVID-19) in New York City. Study design: Retrospective observational study of children 1 month to 21 years admitted March 14 to May 2, 2020, to 9 New York City pediatric intensive care units (PICUs) with severe acute respiratory syndrome coronavirus 2 infection. Results: Of 70 children admitted to PICUs, median age was 15 (IQR 9, 19) years; 61.4% male; 38.6% Hispanic; 32.9% black; and 74.3% with comorbidities. Fever (72.9%) and cough (71.4%) were the common presenting symptoms. Twelve patients (17%) met severe sepsis criteria; 14 (20%) required vasopressor support; 21 (30%) developed acute respiratory distress syndrome (ARDS); 9 (12.9%) met acute kidney injury criteria; 1 (1.4%) required renal-replacement therapy, and 2 (2.8%) had cardiac arrest. For treatment, 27 (38.6%) patients received hydroxychloroquine; 13 (18.6%) remdesivir; 23 (32.9%) corticosteroids; 3 (4.3%) tocilizumab; and 1 (1.4%) anakinra; no patient was given immunoglobulin or convalescent plasma. Forty-nine (70%) patients required respiratory support: 14 (20.0%) noninvasive mechanical ventilation, 20 (28.6%) invasive mechanical ventilation (IMV), 7 (10%) prone position, 2 (2.8%) inhaled nitric oxide, and 1 (1.4%) extracorporeal membrane oxygenation. Nine (45%) of the 20 patients requiring IMV were extubated by day 14 with median IMV duration of 218 (IQR 79, 310.4) hours. Presence of ARDS was significantly associated with duration of PICU and hospital stay, and lower probability of PICU and hospital discharge at hospital day 14 (P < .05 for all). Conclusions: Critically ill children with COVID-19 predominantly are adolescents, have comorbidities, and require some form of respiratory support. The presence of ARDS is significantly associated with prolonged PICU and hospital stay.Publication Open Access How Prepared Are Pediatric Residents for Pediatric Emergencies: Is Pediatric Advanced Life Support Certification Every 2 Years Adequate?(2019-09-16) Doymaz, Sule; Rizvi, Munaza; Orsi, Marguerite; Giambruno, ClaraObjectives. We assessed pediatric residents' retention of knowledge and clinical skills according to the time since their last American Heart Association Pediatric Advanced Life Support (AHA PALS) certification. Methods. Sixty-four pediatric residents were recruited and divided into 3 groups based on the time since their last PALS certification, as follows: group 1, 0 to 8 months; group 2, 9 to 16 months, and group 3, 17 to 24 months. Residents' knowledge was tested using 10 multiple-choice AHA PALS pretest questions and their clinical skills performance was assessed with simulation mock code scenarios using 2 different AHA PALS checklists, and mean scores were calculated for the 3 groups. Differences in the test scores and overall clinical skill performances among the 3 groups were analyzed using analyses of variance, χ2 tests, and Jonckheere-Terpstra tests. Statistical significance was set at P < .05. Results. The pediatric residents' mean overall clinical skills performance scores declined within the first 8 months after their last AHA PALS certification date and continued to decrease over time (87%, 82.6%, and 77.4% for groups 1, 2, and 3, respectively; P = .048). Residents' multiple-choice test scores declined in all 3 groups, but the scores were not significantly different. Conclusions. Residents' clinical skills performance declined within the first 8 months after PALS certification and continued to decline as the time from the last certification increased. Using mock code simulations and reinforcing AHA PALS guidelines during pediatric residency deserve further evaluation.Publication Open Access Risk factors associated with intracranial hemorrhage in neonates with persistent pulmonary hypertension on ECMO.(2015-02-11) Doymaz, Sule; Zinger, Marcia; Sweberg, ToddBackground: Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN. Methods: A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children's hospital. A total number of 32 subjects were studied. Patients with and without ICH during ECMO were evaluated for activated clotting time (ACT), heparin dosing, platelet count, coagulation profile such as activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen level, vital signs including heart rate and mean arterial pressure (MAP), transfusion history, gestational age, and severity of pre-ECMO illness as possible risk factors. Results: Low fibrinogen level (115 ± 13 mg/dl) and low platelet counts (37.4 ± 18.3 Thousand/μl) were associated with higher incidence of ICH (p = 0.009 and p = 0.005, respectively). Elevated MAP (69 ± 4.34 mmHg) was also noticed in ICH patients (p = 0.006). Conclusions: Results demonstrated that low fibrinogen level and low platelet count were associated with ICH in PPHN patients on ECMO. While on ECMO support, maintaining fibrinogen and platelet counts within normal ranges seems crucial to prevent ICH in PPHN patients. This is the first report identifying low fibrinogen level among the risk factors for ICH in infants with PPHN on ECMO support.Publication Open Access Improving the Performance of Residents in Pediatric Resuscitation with Frequent Simulated Codes.(2020-10-30) Doymaz, Sule; Rizvi, Munaza; Giambruno, ClaraAim. Exposure to real codes during pediatric residency training is scarce. Consequently, experiencing mock codes scenarios can provide an opportunity to increase residents' confidence and knowledge in managing pediatric emergencies. Hypothesis. Pediatric senior residents perform better as code team leaders if they are exposed to frequent mock codes. Material and Methods. Forty-three pediatric senior residents (postgraduate year [PGY] two and three) participated in the study. Team leader performance was assessed utilizing the Team Emergency Assessment Measure (TEAM) scoring. Residents' team leadership performance was assessed before and 6 months after the implementation of weekly mock codes. Results. Pediatric residents' team leadership performance in mock codes improved after exposure to weekly practice mock code sessions (71.93 ± 18.50 vs 81.44 ± 11.84, P = 0.01). Conclusion. Increasing the frequency of mock code sessions during residency training led to an improvement in code team leadership performance in pediatric senior residents.Publication Open Access Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents.(2021-08-31) Geva, Alon; Patel, Manish M; Newhams, Margaret M; Young, Cameron C; Son, Mary Beth F; Kong, Michele; Maddux, Aline B; Hall, Mark W; Riggs, Becky J; Singh, Aalok R; Giuliano, John S; Hobbs, Charlotte V; Loftis, Laura L; McLaughlin, Gwenn E; Schwartz, Stephanie P; Schuster, Jennifer E; Babbitt, Christopher J; Halasa, Natasha B; Gertz, Shira J; Doymaz, Sule; Hume, Janet R; Bradford, Tamara T; Irby, Katherine; Carroll, Christopher L; McGuire, John K; Tarquinio, Keiko M; Rowan, Courtney M; Mack, Elizabeth H; Cvijanovich, Natalie Z; Fitzgerald, Julie C; Spinella, Philip C; Staat, Mary A; Clouser, Katharine N; Soma, Vijaya L; Dapul, Heda; Maamari, Mia; Bowens, Cindy; Havlin, Kevin M; Mourani, Peter M; Heidemann, Sabrina M; Horwitz, Steven M; Feldstein, Leora R; Tenforde, Mark W; Newburger, Jane W; Mandl, Kenneth D; Randolph, Adrienne GBackground: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients (N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients (N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.Publication Open Access Early administration of terbutaline in severe pediatric asthma may reduce incidence of acute respiratory failure.(2014-01-25) Doymaz, Sule; Schneider, James; Sagy, MayerBackground: Severe pediatric asthma, if not immediately and aggressively treated, may progress to acute respiratory failure requiring mechanical ventilation in the pediatric intensive care unit (PICU). Intravenous (IV) terbutaline, a β2 agonist, is dispensed when the initial treatment does not improve the clinical condition. Objective: To investigate the influence of early initiation of IV terbutaline on the incidence of acute respiratory failure requiring mechanical ventilation in severe pediatric asthma. Methods: A retrospective chart review was conducted of 120 subjects (35 patients from an outside hospital emergency department [ED] with late start of terbutaline and 85 patients from the authors' hospital ED with early initiation of IV terbutaline) admitted to the PICU with severe asthma treated with continuous IV terbutaline. Responses to terbutaline treatment and outcomes were evaluated. Results: Patients transported from outlying hospital EDs had shorter pre-PICU mean durations of IV terbutaline than those transferred from the authors' ED (0.69 ± 1.38 and 2.91 ± 2.47 hours, respectively, P = .001). Twenty-one of 35 patients (60%) from outlying EDs required mechanical ventilation compared with 14 of 85 patients (16%) from the authors' ED (P = .001). Durations of pre-PICU terbutaline infusion for patients requiring mechanical ventilation were significantly shorter than those with no such requirement (P = .015). Conclusion: The results of the present study, conducted in the largest number of subjects to date, suggest that early administration of continuous terbutaline in the ED may decrease acute respiratory failure and the need for mechanical respiratory (invasive and noninvasive) support in severe pediatric asthma.