IntroductionSepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies.MethodsHere, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up.Ethics and disseminationThis study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming.

Background: Associations among inflammatory cytokines, erythropoietin, and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased erythropoietin would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume.Methods: Prospective observational cohort study of 42 critically ill septic patients. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loos, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming 300 mL RBC = 1 g/dL Hb. Patients with AdjΔHb >0 (+AdjΔHb, n=18) were compared to patients with AdjΔHb ≤0 (−AdjΔHb, n=24).Results: Plasma TNF-alpha, G-CSF, IL-6, IL-8, and erythropoietin, erythrocyte mean corpuscular volume (MCV), and serum transferrin receptor (sTfR) were measured on days 0, 1, 4, 7, and 14. Patients with −AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p<0.05), p=0.01),.5 pg/mL, p=0.01), but not erythropoietin. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r 2 =0.22, p<0.01), IL-8 (r 2 =0.10, p=0.04), SDF-1 (r 2 =0.14, p=0.02), and TNF-alpha (r 2 =0.13, p=0.02), but not erythropoietin.

Key Points Question Can a whole-blood RNA transcriptomic metric (IMX) obtained in the first 12 hours after intensive care unit (ICU) admission accurately measure the presence of bacterial infection and risk for sepsis mortality? Findings In this diagnostic and prognostic study including 200 patients with critical illness enrolled from a surgical ICU, the IMX transcriptomic metric was equivalent to or significantly better than the sequential organ failure assessment score and existing biomarkers (procalcitonin and interleukin 6 levels) for the diagnosis of acute infections and estimation of 30-day mortality. Meaning These findings suggest that a single, rapid-turnaround, multivalent transcriptomic test could supplant existing metrics in identifying bacterial infection and estimating clinical outcomes among critically ill surgical patients.