William Ottestad1,2, Ingrid N Rognes2, Soeren E Pischke1,3, Tom E Mollnes3,4,5, Ulf Andersson6, Torsten Eken1,2. 1. Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway. 2. Division of Critical Care, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 3. Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Oslo, Norway. 4. Research Laboratory, Nordland Hospital, Bodø, and Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway. 5. Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. 6. Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Abstract
OBJECTIVES: The causal role of the prototype alarmin high mobility group box 1 protein in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim was therefore to determine high mobility group box 1 protein concentration kinetics with high time resolution during the first hours after trauma in individual patients and investigate the association with outcome. DESIGN: Prospective single-center observational study. SETTING: University hospital Level I trauma center. PATIENTS: Convenience recruitment of 136 trauma patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total plasma high mobility group box 1 protein levels were analyzed with enzyme-linked immunosorbent assay in repeated samples. Relationships between predefined predictor variables and outcome were examined in multivariable linear regression models. Ventilator-free days was used as primary outcome measure. Two distinct high mobility group box 1 protein release phases were identified. An initial exponential decay phase with half-life 26 minutes was not correlated with outcome. In contrast, a second high mobility group box 1 protein wave peaking 3-6 hours after trauma in the most severely injured and physiologically deranged patients was consistently the most important predictor of outcome in our multivariable models, rendering all other predictor variables insignificant except for smaller contributions from age and sex, and of admission base excess for maximal creatinine concentration. CONCLUSIONS: High mobility group box 1 protein was released in two consecutive phases. Only the second high mobility group box 1 protein wave was a significant predictor of outcome. Patients with a high high mobility group box 1 protein concentration between 3 and 6 hours after trauma might hypothetically benefit from high mobility group box 1 protein-specific antagonist therapy.
OBJECTIVES: The causal role of the prototype alarmin high mobility group box 1 protein in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim was therefore to determine high mobility group box 1 protein concentration kinetics with high time resolution during the first hours after trauma in individual patients and investigate the association with outcome. DESIGN: Prospective single-center observational study. SETTING: University hospital Level I trauma center. PATIENTS: Convenience recruitment of 136 traumapatients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total plasma high mobility group box 1 protein levels were analyzed with enzyme-linked immunosorbent assay in repeated samples. Relationships between predefined predictor variables and outcome were examined in multivariable linear regression models. Ventilator-free days was used as primary outcome measure. Two distinct high mobility group box 1 protein release phases were identified. An initial exponential decay phase with half-life 26 minutes was not correlated with outcome. In contrast, a second high mobility group box 1 protein wave peaking 3-6 hours after trauma in the most severely injured and physiologically deranged patients was consistently the most important predictor of outcome in our multivariable models, rendering all other predictor variables insignificant except for smaller contributions from age and sex, and of admission base excess for maximal creatinine concentration. CONCLUSIONS:High mobility group box 1 protein was released in two consecutive phases. Only the second high mobility group box 1 protein wave was a significant predictor of outcome. Patients with a high high mobility group box 1 protein concentration between 3 and 6 hours after trauma might hypothetically benefit from high mobility group box 1 protein-specific antagonist therapy.
Authors: Olav Sundnes; William Ottestad; Guttorm Haraldsen; Torsten Eken; Camilla Schjalm; Peter Lundbäck; Lars la Cour Poulsen; Tom Eirik Mollnes Journal: Mol Med Date: 2021-03-26 Impact factor: 6.354
Authors: William Ottestad; Ingrid N Rognes; Erlend Skaga; Cassandra Frisvoll; Guttorm Haraldsen; Torsten Eken; Peter Lundbäck Journal: Mol Med Date: 2019-12-31 Impact factor: 6.354
Authors: Zhangsheng Yang; Milomir O Simovic; Peter R Edsall; Bin Liu; Tomas S Cancio; Andriy I Batchinsky; Leopoldo C Cancio; Yansong Li Journal: Biomolecules Date: 2022-01-08