RESUMO
BACKGROUND: Complement activation is a central mechanism in systemic inflammation and remote organ dysfunction following major trauma. Data on temporal changes of complement activation early after injury is largely missing. We aimed to describe in detail the kinetics of complement activation in individual trauma patients from admission to 10 days after injury, and the association with trauma characteristics and outcome. METHODS: In a prospective cohort of 136 trauma patients, plasma samples obtained with high time resolution (admission, 2, 4, 6, 8 h, and thereafter daily) were assessed for terminal complement complex (TCC). We studied individual TCC concentration curves and calculated a summary measure to obtain the accumulated TCC response 3 to 6 h after injury (TCC-AUC3-6). Correlation analyses and multivariable linear regression analyses were used to explore associations between individual patients' admission TCC, TCC-AUC3-6, daily TCC during the intensive care unit stay, trauma characteristics, and predefined outcome measures. RESULTS: TCC concentration curves showed great variability in temporal shapes between individuals. However, the highest values were generally seen within the first 6 h after injury, before they subsided and remained elevated throughout the intensive care unit stay. Both admission TCC and TCC-AUC3-6 correlated positively with New Injury Severity Score (Spearman's rho, p-value 0.31, 0.0003 and 0.21, 0.02) and negatively with admission Base Excess (- 0.21, 0.02 and - 0.30, 0.001). Multivariable analyses confirmed that deranged physiology was an important predictor of complement activation. For patients without major head injury, admission TCC and TCC-AUC3-6 were negatively associated with ventilator-free days. TCC-AUC3-6 outperformed admission TCC as a predictor of Sequential Organ Failure Assessment score at day 0 and 4. CONCLUSIONS: Complement activation 3 to 6 h after injury was a better predictor of prolonged mechanical ventilation and multiple organ dysfunction syndrome than admission TCC. Our data suggest that the greatest surge of complement activation is found within the first 6 h after injury, and we argue that this time period should be in focus in the design of future experimental studies and clinical trials using complement inhibitors.
Assuntos
Ativação do Complemento , Traumatismos Craniocerebrais/imunologia , Insuficiência de Múltiplos Órgãos/imunologia , Respiração Artificial , Ferimentos e Lesões/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Traumatismos Craniocerebrais/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Síndrome , Fatores de Tempo , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
BACKGROUND: Trauma patients have high concentrations of circulating extracellular vesicles (EVs) following injury, but the functional role of EVs in this setting is only partly deciphered. We aimed to describe in detail EV-associated procoagulant activity in individual trauma patients during the first 12 hours after injury to explore their putative function and relate findings to relevant trauma characteristics and outcome. METHODS: In a prospective observational study of 33 convenience recruited trauma patients, citrated plasma samples were obtained at trauma center admission and 2, 4, 6, and 8 hours thereafter. We measured thrombin generation from isolated EVs and the procoagulant activity of phosphatidylserine (PS)-exposing EVs. Correlation and multivariable linear regression analyses were used to explore associations between EV-associated procoagulant activity and trauma characteristics as well as outcome measures. RESULTS: EV-associated procoagulant activity was highest in the first 3 hours after injury. EV-associated thrombin generation normalized within 7 to 12 hours of injury, whereas the procoagulant activity of PS-exposing EVs declined to a level right above that of healthy volunteers. Increased EV-associated procoagulant activity at admission was associated with higher New Injury Severity Score, lower admission base excess, higher admission international normalized ratio, prolonged admission activated partial thromboplastin time, higher Sequential Organ Failure Assessment score at day 0, and fewer ventilator-free days. CONCLUSION: Our data suggest that EVs have a transient hypercoagulable function and may play a role in the early phase of hemostasis after injury. The role of EVs in trauma-induced coagulopathy and posttraumatic thrombosis should be studied bearing in mind this novel temporal pattern. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level V.
Assuntos
Vesículas Extracelulares/metabolismo , Hemostasia/fisiologia , Trombina/metabolismo , Trombose/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Fosfatidilserinas/sangue , Fosfatidilserinas/metabolismo , Projetos Piloto , Estudos Prospectivos , Trombina/análise , Trombose/diagnóstico , Trombose/etiologia , Fatores de Tempo , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Adulto JovemRESUMO
Laparoscopic and open liver resection have not been compared in randomized trials. The aim of the current study was to compare the inflammatory response after laparoscopic and open resection of colorectal liver metastases (CLM) in a randomized controlled trial.This was a predefined exploratory substudy within the Oslo CoMet-study. Forty-five patients with CLM were randomized to laparoscopic (n = 23) or open (n = 22) resection. Ethylenediaminetetraacetic acid-plasma samples were collected preoperatively and at defined time points during and after surgery and snap frozen at -80 C. A total of 25 markers were examined using luminex and enzyme-linked immunosorbent assay techniques: high-mobility box group 1(HMGB-1), cell-free DNA (cfDNA), cytokines, and terminal C5b-9 complement complex complement activation.Eight inflammatory markers increased significantly from baseline: HMGB-1, cfDNA, interleukin (IL)-6, C-reactive protein, macrophage inflammatory protein -1ß, monocyte chemotactic protein -1, IL-10, and terminal C5b-9 complement complex. Peak levels were reached at the end of or shortly after surgery. Five markers, HMGB-1, cfDNA, IL-6, C-reactive protein, and macrophage inflammatory protein -1ß, showed significantly higher levels in the open surgery group compared with the laparoscopic surgery group.Laparoscopic resection of CLM reduced the inflammatory response compared with open resection. The lower level of HMGB-1 is interesting because of the known association with oncogenesis.