A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score

Abstract

Background Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. Research question As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. Study design and methods This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. Results After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10− CD16−) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). Interpretation We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies. Graphical Abstract

Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients

“…These results are in line with recent biomarker development, which combined pro and anti-inflammatory markers to improve prediction of deleterious outcomes such as secondary infections ( 45 , 46 ). This was, for example, described in trauma patients with the association of plasma IL-6 levels and mHLA-DR ( 47 ).…”

Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study

“…In addition, this threshold is currently used in ongoing trials (NCT02361528 and NCT04990232). Notably, recent observational studies ( 21 , 22 ) also reported on this threshold to define groups of patients at increased risk of deleterious outcomes and similarly used 8,000 AB/C as a threshold for identifying immunosuppression. That said, next prospective investigations may focus on a more continuous adjustment of the IPP algorithm according to various levels of immunosuppression.…”

A Multicentric Observational Study to Determine Myocardial Injury in Severe Community-Acquired Pneumonia (sCAP)

“…This was a multicenter prospective cohort analysis (ClinicalTrials.gov Identifier: NCT03058211) (accessed on 1 July 2021) [11]. The baseline characteristics, clinical outcomes, and prognostic factors related to myocardial damage were assessed.…”