Guus P Leijte1,2, Thomas Rimmelé3,4, Matthijs Kox1,2, Niklas Bruse1,2, Céline Monard4, Morgane Gossez3,5, Guillaume Monneret3,5, Peter Pickkers1,2, Fabienne Venet6,7. 1. Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. 2. Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. 3. Pathophysiology of Injury-Induced Immunosuppression, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, bioMérieux, Edouard Herriot Hospital, 5 place d'Arsonval, 69437, Lyon Cedex 03, France. 4. Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. 5. Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. 6. Pathophysiology of Injury-Induced Immunosuppression, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, bioMérieux, Edouard Herriot Hospital, 5 place d'Arsonval, 69437, Lyon Cedex 03, France. fabienne.venet@chu-lyon.fr. 7. Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. fabienne.venet@chu-lyon.fr.
Abstract
BACKGROUND: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. METHODS: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. RESULTS: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). CONCLUSION: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.
BACKGROUND: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. METHODS: We evaluated mHLA-DR expression kinetics in 241 septic shockpatients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. RESULTS: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). CONCLUSION: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shockpatients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shockpatients.
Entities:
Keywords:
Adverse outcome; Infection-free survival; Mortality; Pathogens; Secondary infections; Septic shock; Site of infection; Trajectory analysis; mHLA-DR
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