Medicine and Health Sciences Commons^™

Data-Driven Clustering Identifies Features Distinguishing Multisystem Inflammatory Syndrome From Acute Covid-19 In Children And Adolescents., Alon Geva, Manish M. Patel, Margaret M. Newhams, Cameron C. Young, Mary Beth F. Son, Michele Kong, Aline B. Maddux, Mark W. Hall, Becky J. Riggs, Aalok R. Singh, John S. Giuliano, Charlotte V. Hobbs, Laura L. Loftis, Gwenn E. Mclaughlin, Stephanie P. Schwartz, Jennifer E. Schuster, Christopher J. Babbitt, Natasha B. Halasa, Shira J. Gertz, Sule Doymaz, Janet R. Hume, Tamara T. Bradford, Katherine Irby, Christopher L. Carroll, John K. Mcguire, Keiko M. Tarquinio, Courtney M. Rowan, Elizabeth H. Mack, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Philip C. Spinella, Mary A. Staat, Katharine N. Clouser, Vijaya L. Soma, Heda Dapul, Mia Maamari, Cindy Bowens, Kevin M. Havlin, Peter M. Mourani, Sabrina M. Heidemann, Steven M. Horwitz, Leora R. Feldstein, Mark W. Tenforde, Jane W. Newburger, Kenneth D. Mandl, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

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)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 …

Pooled Safety Analysis Of Tisagenlecleucel In Children And Young Adults With B Cell Acute Lymphoblastic Leukemia., John E. Levine, Stephan A. Grupp, Michael A. Pulsipher, Andrew C. Dietz, Susana Rives, Douglas Myers, Keith August, Michael R. Verneris, Jochen Buechner, Theodore W. Laetsch, Henrique Bittencourt, Andre Baruchel, Michael W. Boyer, Barbara De Moerloose, Muna Qayed, Stella M. Davies, Christine L. Phillips, Timothy A. Driscoll, Peter Bader, Krysta Schlis, Patricia A. Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K. Eldjerou, Carl H. June, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.

Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.

Results: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of …

A Multicenter Evaluation Of Viral Bloodstream Detections In Children Presenting To The Emergency Department With Suspected Systemic Infection., Christina A. Rostad, Neena Kanwar, Jumi Yi, Claudia R. Morris, Jennifer Dien Bard, Amy Leber, James Dunn, Kimberle C. Chapin, Anne J. Blaschke, Judy A. Daly, Leslie Hueschen, Matthew Jones, Elizabeth Ott, Jeffrey Bastar, Kevin M. Bourzac, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections.

METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted.

RESULTS: Of the 1114 subjects enrolled, …

Factors Associated With Reduced Infliximab Exposure In The Treatment Of Pediatric Autoimmune Disorders: A Cross-Sectional Prospective Convenience Sampling Study., Ryan S. Funk, Valentina Shakhnovich, Yu Kyoung Cho, Kishore Polireddy, Taina Hudson, Kyle Gress, Mara L. Becker

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy.

METHODS: In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient …

Leveraging Institutional Support To Build An Integrated Multidisciplinary Care Model In Pediatric Inflammatory Bowel Disease., Jennifer Verrill Schurman, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

While the biopsychosocial nature of inflammatory bowel disease (IBD) is now well accepted by clinicians, the need for integrated multidisciplinary care is not always clear to institutional administrators who serve as decision makers regarding resources provided to clinical programs. In this commentary, we draw on our own experience in building successful integrated care models within a division of pediatric gastroenterology (GI) to highlight key considerations in garnering initial approval, as well as methods to maintain institutional support over time. Specifically, we discuss the importance of making a strong case for the inclusion of a psychologist in pediatric IBD care, justifying …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …