2.1. Study design

Our study design was previously reported by Darden et al. (14). To summarize, this prospective, observational cohort study was registered with clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT02276417","term_id":"NCT02276417"}}NCT02276417) and conducted at a tertiary care, academic research hospital. The objective of the study was to better understand the myeloid response (specifically blood MDSCs) to acute sepsis, and to identify transcriptomic differences in sepsis patients who rapidly recover versus those who develop CCI. Our hypothesis was that differences in the myeloid transcriptomic landscape could explain why some sepsis patients rapidly recover while others develop CCI.

Sepsis designation occurred through an electronic medical record-based Modified Early Warning Signs-Sepsis Recognition System (MEWS-SRS), which uses white blood cell count, heart rate, respiration rate, blood pressure, and mental status to identify patients at risk for sepsis. All patients with sepsis were treated with early goal-directed fluid administration, initiation of broad-spectrum antibiotics, and vasopressor administration if appropriate. Antibiotic treatment was tailored to culture results and antibiotic resistance information.

Inclusion criteria:

Exclusion criteria:

CCI was defined as ICU length of stay >13 days with persistent organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. Patients were also designated CCI with <14 days ICU length of stay if they were transferred to another hospital, or discharged to a long-term acute care facility or hospice with evidence of persistent organ dysfunction (4, 16).