PROJECT SUMMARY/ABSTRACT – Children’s Hospital Los Angeles This application details the qualifications, interest and commitment of Children’s Hospital Los Angeles (CHLA) to be a member of the Collaborative Pediatric Critical Care Research Network (CPCCRN). CHLA and its investigators in the division of critical care are international experts in pediatric mechanical ventilation, Pediatric Acute Respiratory Distress Syndrome (PARDS), informatics and data science. Led by Dr. Khemani (PI) and Dr. Newth (Co-I), the multi-disciplinary CHLA respiratory research group and its members have led large multi-center observational studies in PARDS (PARDIE study, 145 international ICUs), and have spearheaded international practice guidelines related to mechanical ventilation and PARDS. This group is currently running a highly innovative single center clinical trial using a computerized decision support tool targeting lung and diaphragm protective ventilation in pediatric ARDS, which includes comprehensive assessment of post-ICU morbidity. These unique qualifications and expertise will greatly enrich the scientific rigor and breadth of knowledge within the CPCCRN. In addition, other CHLA investigators are pioneers in data science, neurocritical care and implementation science, and will bring this expertise to the CPCCRN. CHLA is at the forefront of collaborative research, with several faculty holding leadership positions in the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the Pediatric Neurocritical Care Research Group, and multi-center data collaboratives such as VPS, VPICU, and the PICU Data Collaborative. This expertise underscores our faculty’s ability to be highly collaborative in a research network to achieve common goals. It is therefore not surprising that CHLA has been the highest enroller in a multitude of multi-center clinical trials and observational studies in pediatric critical care. To further enhance our ability to recruit a large number of diverse patients into the CPCCRN studies, we will partner with an ancillary site at Children’s Hospital of Orange County (CHOC). CHOC has been participating in multi-center collaborative research through the PALISI network for over 10 years and has also achieved remarkably high enrollment rates in clinical trials. Through our two centers, we can ensure that the clinical trial(s) conducted in the CPCCRN capture the unique ethnic, racial, and socio-economic diversity of Southern California which includes > 50% of patients being of Hispanic ethnicity. This is imperative for the proposed clinical trial on immune-modulation in sepsis, given the impact that genetic, epigenetic, environmental, and socio-economic factors may have on treatment and outcomes. Our site has several highly talented faculty and junior investigators who will not only contribute to the success of the CPCCRN but can be further mentored and developed into future thought leaders and clinical/tr...