PROJECT SUMMARY/ABSTRACT – Baylor College of Medicine/Texas Children's Hospital The goals of the current proposal are to reorganize and expand the Collaborative Pediatric Critical Care Research Network (CPCCRN), to mentor young investigators in CPCCRN to become independent investigators, and to implement the multi-center randomized controlled “Personalized Immunomodulation in Sepsis-Induced Multiple Organ Dysfunction” interventional trial. The newly organized CPCCRN will expand from 7 to 24 clinical sites (12 Primary and 12 Ancillary sites), which will be the largest NIH Pediatric Critical Care Research Network to date. We at Baylor College of Medicine (BCM) - Texas Children's Hospital (TCH; Primary Site) and Children's Hospital of San Antonio (CHofSA; Ancillary Site) are very enthusiastic about participating as new sites. TCH is the largest freestanding children's hospital system in the U.S. and is one of the best (Rank #4 Children's Hospital by U.S. News & World Report 2020-2021). We have every pediatric subspecialty and offer every service expected in a quaternary pediatric center. We have an extensive track record of successful collaboration in multi-center clinical trials such as the Pediatric Acute Lung Injury and Sepsis Investigators and the Pediatric Heart Network. In combination with our CHofSA partner, we will provide access to 163+24 beds with 6000 annual admissions, enabling us to participate fully in the “Personalized Immunomodulation in Sepsis-induced Multiple Organ Dysfunction (MODS)” trial described in the Overall Component of this application. Our sites have several highly talented young faculty, who have career development grants with innovative translational research projects, and will contribute to the success of CPCCRN. For example, Dr. Desai (K12 recipient) pioneered the field of pediatric cirrhotic cardiomyopathy and bile acid-myocardial interaction (cholecardia). His aim is to improve outcomes of pediatric liver failure through decreasing circulating pathologic bile acids by novel bile acid sequestrants and blood purification techniques. Dr. Lam (K08 recipient) develops novel protein to attenuate inflammation through inhibiting leukocyte-platelet- endothelial interactions. His aim is to improve outcomes in pediatric liver failure and more recently, COVID19- induced inflammation. Dr. Nguyen, our Co-Investigator, is R01 funded to study mechanisms of sepsis-induced MODS and to develop targeted novel agent for this deadly disease. His aim is to obtain Investigational New Drug status for his novel A2 Protein from the Food and Drug Administration, and subsequently, to enter A2 Protein in clinical trials such as CPCCRN. Dr. Arikan, our site Principle Investigator, plans to study the impact of extracorporeal therapies in immunomodulation and pharmacokinetics of novel therapeutics to build on her previous work in pediatric MODS with a special emphasis on interaction of acute kidney injury, acquired immune dysfunction, and MODS phen...