WIP 85 - PICS-ating on the Heart: Immunometabolic Dysregulation in Children with Congenital Heart Disease and PICS (Persistent Inflammation, Immunosuppression, and Catabolism Syndrome)

Publication Number: WIP 85.7484

Natalya M. Beneschott, Vanderbilt University Medical Center, Nashville, TN, United States; Sandra Yoder, Vanderbilt Univ Med Ctr, Nashville, TN, United States; Eric Brady, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, United States; C. Buddy Creech, Vanderbilt University School of Medicine, Nashville, TN, United States

Background: Many patients with chronic critical illness have variable recovery from acute events, such as surgery or sepsis, and experience dysregulated inflammation, blunted immune responses, and recurrent infections. This phenomenon is called persistent inflammation, immunosuppression, and catabolism syndrome (PICS) and is associated with poor wound healing and indolent organ failure. The pathophysiology of PICS has not been characterized in critically ill pediatric populations, particularly those with congenital heart disease (CHD).

Objective: We are investigating the functional immunity and metabolomic signatures in critically ill pediatric patients with CHD. By characterizing the spectrum of immunometabolic dysfunction, we could help discover potential diagnostic markers or specific immunomodulatory and metabolic therapeutics to restore immune homeostasis in these patients as they recover from surgical repair.

Design/Methods: This observational cohort study was approved by the Vanderbilt IRB as no greater than minimal risk to participants. Twenty-seven hospitalized children who underwent CHD repair were enrolled in one of the following groups. Group 1 participants underwent major CHD repair and were enrolled before the development of infection or PICS. Group 2 had developed an acute bacterial Infection. Group 3 had PICS at enrollment and met 2 of the 3 PICS criteria defined as lymphopenia (ALC < 1500 cells/uL), elevated CRP (> 10 mg/dL), and hypoalbuminemia ( < 3.0 mg/dL). Group 4 had rapid recovery after surgical repair with uncomplicated hospitalizations. Groups 1 – 3 underwent weekly blood and urine sampling for up to 1 month during admission. Group 4 had a single sample collection near discharge.

Plasma cytokines were investigated using a 25-plex antibody bead panel. Non-parametric Wilcoxon rank-sum testing was performed. Additional analysis to be completed in the following calendar year includes immunophenotyping by flow cytometry, bioenergetics via single-cell energetic metabolism by profiling translation inhibition (SCENITH) technology, and urine metabolomics.