Browsing by Author "Giuliano, John S."

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    Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19
    (AMA, 2021-02) 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 G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Importance 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.
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    Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents
    (Elsevier, 2021-08-31) Geva, Alon; Patel, Manish M.; 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 G.; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background 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.
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    Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children
    (Oxford University Press, 2023) Halasa, Natasha B.; Spieker, Andrew J.; Young, Cameron C.; Olson, Samantha M.; Newhams, Margaret M.; Amarin, Justin Z.; Moffitt, Kristin L.; Nakamura, Mari M.; Levy, Emily R.; Soma, Vijaya L.; Talj, Rana; Weiss, Scott L.; Fitzgerald, Julie C.; Mack, Elizabeth H.; Maddux, Aline B.; Schuster, Jennifer E.; Coates, Bria M.; Hall, Mark W.; Schwartz, Stephanie P.; Schwarz, Adam J.; Kong, Michele; Spinella, Philip C.; Loftis, Laura L.; McLaughlin, Gwenn E.; Hobbs, Charlotte V.; Rowan, Courtney M.; Bembea, Melania M.; Nofziger, Ryan A.; Babbitt, Christopher J.; Bowens, Cindy; Flori, Heidi R.; Gertz, Shira J.; Zinter, Matt S.; Giuliano, John S.; Hume, Janet R.; Cvijanovich, Natalie Z.; Singh, Aalok R.; Crandall, Hillary A.; Thomas, Neal J.; Cullimore, Melissa L.; Patel, Manish M.; Randolph, Adrienne G.; Pediatric Intensive Care Influenza; Overcoming COVID-19 Investigators; Pediatrics, School of Medicine
    Background: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. Results: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32). Conclusions: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.
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    Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
    (AMA, 2021-03) 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 G.; Overcoming COVID-19 Investigators; Gaspers, Mary G; Typpo, Katri V; Sanders, Ronald C; Schwarz, Adam J; Harvey, Helen; Zinter, Matt S; Mourani, Peter M; Coates, Bria M; Bhoojhawon, Guru; Havlin, Kevin M; Montgomery, Vicki L; Sullivan, Janice E; Bradford, Tamara T; Bembea, Melania M; Lipton, Susan V; Graciano, Ana Lia; Chen, Sabrina R; Kucukak, Suden; Newburger, Jane W; Carroll, Ryan W; Fernandes, Neil D; Yager, Phoebe H; Marohn, Kimberly L; Heidemann, Sabrina M; Cullimore, Melissa L; McCulloh, Russell J; Horwitz, Steven M; Li, Simon; Walsh, Rowan F; Ratner, Adam J; Soma, Vijaya L; Gillen, Jennifer K; Zackai, Sheemon P; Ackerman, Kate G; Cholette, Jill M; Harwayne-Gidansky, Ilana; Hymes, Saul R; Overby, Philip J; Schwartz, Stephanie P; Lansell, Amanda N; Koncicki, Monica L; Carcillo, Joseph; Fink, Ericka; Kimura, Dai; Bowens, Cindy; Crandall, Hillary; Smith, Lincoln S; Cengiz, Pelin; Pediatrics, School of Medicine
    Importance 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.
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    Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary
    (American Academy of Pediatrics, 2022) Bembea, Melania M.; Agus, Michael; Akcan-Arikan, Ayse; Alexander, Peta; Basu, Rajit; Bennett, Tellen D.; Bohn, Desmond; Brandão, Leonardo R.; Brown, Ann-Marie; Carcillo, Joseph A.; Checchia, Paul; Cholette, Jill; Cheifetz, Ira M.; Cornell, Timothy; Doctor, Allan; Eckerle, Michelle; Erickson, Simon; Farris, Reid W.D.; Faustino, E. Vincent S.; Fitzgerald, Julie C.; Fuhrman, Dana Y.; Giuliano, John S.; Guilliams, Kristin; Gaies, Michael; Gorga, Stephen M.; Hall, Mark; Hanson, Sheila J.; Hartman, Mary; Hassinger, Amanda B.; Irving, Sharon Y.; Jeffries, Howard; Jouvet, Philippe; Kannan, Sujatha; Karam, Oliver; Khemani, Robinder G.; Kissoon, Niranjan; Lacroix, Jacques; Laussen, Peter; Leclerc, Francis; Lee, Jan Hau; Leteurtre, Stephane; Lobner, Katie; McKiernan, Patrick J.; Menon, Kusum; Monagle, Paul; Muszynski, Jennifer A.; Odetola, Folafoluwa; Parker, Robert; Pathan, Nazima; Pierce, Richard W.; Pineda, Jose; Prince, Jose M.; Robinson, Karen A.; Rowan, Courtney M.; Ryerson, Lindsay M.; Sanchez-Pinto, L. Nelson; Schlapbach, Luregn J.; Selewski, David T.; Shekerdemian, Lara S.; Simon, Dennis; Smith, Lincoln S.; Squires, James E.; Squires, Robert H.; Sutherland, Scott M.; Ouellette, Yves; Spaeder, Michael C.; Srinivasan, Vijay; Steiner, Marie E.; Tasker, Robert C.; Thiagarajan, Ravi; Thomas, Neal; Tissieres, Pierre; Traube, Chani; Tucci, Marisa; Typpo, Katri V.; Wainwright, Mark S.; Ward, Shan L.; Watson, R. Scott; Weiss, Scott; Whitney, Jane; Willson, Doug; Wynn, James L.; Yehya, Nadir; Zimmerman, Jerry J.; Pediatrics, School of Medicine
    Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.