Monocytic HLA-DR expression and clinical outcomes in adult ICU patients with sepsis – a systematic review and meta-analysis

Review question / Objective: The scope of this review was defined using PICOTS framework where 1) population: adult critically ill patients with sepsis or septic shock; 2) index prognostic factor: cell surface protein expression of mHLA-DR in blood; 3) comparative factor: none; 4) outcomes to be predicted: mortality, secondary infections, length of stay, and organ dysfunction score (sequential organ failure assessment [SOFA], multiple organ dysfunction score [MODS], logistic organ dysfunction score [LODS]), composite outcomes where component endpoints consist of at least one of the outcomes stated above (e.g., “adverse outcome” defined as death or secondary infection), 5) timing (of the prediction horizon and the moment of prognosis): any; and 6) setting: ICU. Condition being studied: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to severe infections. It can further progress to septic shock, which includes hemodynamic failure and increased mortality rates. A recent worldwide epidemiological study estimated 48.9 million sepsis cases and 11 million of sepsis-related deaths (~20% of global deaths in 2017). Although its management has advanced considerably, sepsis remains deadly and challenging to treat. The 28/30-day mortality averages around 25% for sepsis and 38% for septic shock in high-income countries. Current models describe the underlying pathophysiologic mechanisms of sepsis as an interplay between concurrent dysfunctional pro- and anti-inflammatory immune response.