The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients.

BACKGROUND: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells. METHODS: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28. RESULTS: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups. CONCLUSION: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.

The role of neutrophil chemotaxis activity as an immunologic biomarker to predict mortality in critically-ill patients with severe sepsis.

BACKGROUND: Innate immunity is an important host response to infection. However, the role of innate immunity as a prognostic biomarker in severe sepsis is still unknown. This study is to evaluate the discriminatory characteristics of these biomarkers on clinical outcome. MATERIALS AND METHODS: Retrospective study was conducted in critically ill patients with severe sepsis. Neutrophil function was assessed by neutrophil chemotaxis activity and CD-11b expression. Monocyte function was assessed by measurement of mHLA-DR expression and presepsin level. The primary end point was 28 day-mortality. RESULTS: A total of 136 participants were enrolled. Patients were classified into 2 groups as survivors (n = 63, 46.3%) and non-survivors (n = 73, 53.7%). Neutrophil chemotaxis activity was significantly higher in survivors (46.7% vs. 41.2%, p = .023). There was no difference in the remaining biomarker levels between survivors and non-survivors. Only decreased neutrophil chemotaxis activity was associated with 28-day mortality. Combining neutrophil chemotaxis activity with mHLA-DR, CD-11b expression, presepsin, and SOFA score provided the highest AUC of 0.90 (0.84-0.96) in predicting 28-day mortality. CONCLUSION: Neutrophil chemotaxis activity appears to be a promising novel immunologic biomarker in predicting clinical outcome in patients with severe sepsis.