The Potential of Adipokines in Identifying Multiple Trauma Patients at Risk of Developing Multiple Organ Dysfunction Syndrome

Abstract BackgroundMultiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS.MethodsIn total, 14 multiple trauma patients with an injury severity score (ISS) ³ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA. ResultsIn the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF. ConclusionsThe results of this study may contribute to identify severely injured patients with a developing SIRS and MOF earlier, in order to adjust therapy strategies.

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The potential of adipokines in identifying multiple trauma patients at risk of developing multiple organ dysfunction syndrome

European Journal of Medical Research ◽

10.1186/s40001-021-00511-z ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Julian Haupt ◽

Niels Krysiak ◽

Marina Unger ◽

Viktoria Bogner-Flatz ◽

Peter Biberthaler ◽

...

Keyword(s):

Multiple Trauma ◽

Organ Dysfunction ◽

Multiple Organ Dysfunction Syndrome ◽

Plasma Concentrations ◽

Multiple Organ ◽

Control Group ◽

Trauma Patients ◽

Multiple Organ Dysfunction ◽

Patients At Risk ◽

Multiple Trauma Patients

Abstract Background Multiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS. Methods In total, 14 multiple trauma patients with an injury severity score (ISS) ≥ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72 h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA. Results In the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF. Conclusions Leptin and IL-17A could be suitable diagnostic markers to identify severely injured patients with a developing SIRS and MOF earlier, to adjust surgical therapy planning and intensive care.

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Early increase in anti-inflammatory biomarkers is associated with the development of multiple organ dysfunction syndrome in severely injured trauma patients

Trauma Surgery & Acute Care Open ◽

10.1136/tsaco-2019-000343 ◽

2019 ◽

Vol 4 (1) ◽

pp. e000343 ◽

Cited By ~ 1

Author(s):

Derek JB Kleinveld ◽

Anita M Tuip-de Boer ◽

Markus W Hollmann ◽

Nicole P Juffermans

Keyword(s):

Multiple Trauma ◽

Inflammatory Cytokines ◽

Multiple Organ ◽

Trauma Patients ◽

Severely Injured ◽

Multiple Organ Dysfunction ◽

Patients At Risk ◽

Inflammatory Proteins ◽

Anti Inflammatory ◽

Multiple Trauma Patients

BackgroundAs a result of improvements in the early resuscitation phase of trauma, mortality is largely driven by later mortality due to multiple organ dysfunction syndrome (MODS), which may be mediated by an early overdrive in the host immune response. If patients at risk for MODS could be identified early, preventive treatment measures could be taken. The aim of this study is to investigate whether specific biomarkers are associated with MODS.MethodsMultiple trauma patients presenting to the Amsterdam University Medical Centers, location Academic Medical Center, between 2012 and 2018 with an Injury Severity Score of 16 or higher were sampled on arrival at the emergency department. A wide variety of inflammatory cytokines, endothelial and lung-specific markers were determined. Comparisons were made between patients with and without MODS. Univariate and multivariate logistic regression was used to determine associations between specific biomarkers and MODS. A p value of 0.05 was considered to be statistically significant.ResultsIn total, 147 multiple trauma patients were included. Of these, 32 patients developed MODS (21.7%). Patients who developed MODS were more severely injured, had more traumatic brain injury and showed more deranged markers of coagulation when compared with patients without MODS. Overall, both proinflammatory and anti-inflammatory cytokines were higher in patients with MODS, indicative of a host immune reaction. In the multivariate analysis, the combination of anti-inflammatory proteins interleukin 1 receptor antagonist (IL-1RA) (OR 1.27 (1.07–1.51), p=0.002) and Clara cell protein 16 (CC-16) (1.06 (1.01–1.05), p=0.031) was most strongly associated with the development MODS.ConclusionsIn trauma, anti-inflammatory proteins IL-1RA and CC-16 have the potential to early identify patients at risk for development of MODS. Further research is warranted to prospectively validate these results.Level of evidencePrognostic study, level III.

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IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2018.8.jns18676 ◽

2019 ◽

Vol 131 (6) ◽

pp. 1931-1937 ◽

Cited By ~ 2

Author(s):

Sungho Lee ◽

Hyunsoo Hwang ◽

Jose-Miguel Yamal ◽

J. Clay Goodman ◽

Imoigele P. Aisiku ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Organ Dysfunction ◽

Multiple Organ Dysfunction Syndrome ◽

Sofa Score ◽

Plasma Concentrations ◽

Multiple Organ ◽

Multiple Organ Dysfunction ◽

Poor Outcome ◽

Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

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Microparticles from Patients with Multiple Organ Dysfunction Syndrome and Sepsis Support Coagulation through Multiple Mechanisms

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615753 ◽

2001 ◽

Vol 85 (05) ◽

pp. 810-820 ◽

Cited By ~ 164

Author(s):

Karin Joop ◽

René Berckmans ◽

Rienk Nieuwland ◽

Johanna Berkhout ◽

Fred Romijn ◽

...

Keyword(s):

Organ Dysfunction ◽

Multiple Organ Dysfunction Syndrome ◽

Plasma Concentrations ◽

Annexin V ◽

Multiple Organ ◽

Factor Xii ◽

Healthy Controls ◽

Multiple Organ Dysfunction ◽

Coagulation Activation

Summary Aim. We investigated the occurrence and thrombin generating mechanisms of circulating microparticles (MP) in patients with multiple organ dysfunction syndrome (MODS) and sepsis. Methods. MP, isolated from blood of patients (n = 9) and healthy controls (n = 14), were stained with cell-specific monoclonal antibodies (MoAbs) or anti-tissue factor (anti-TF) MoAb and annexin V, and analyzed by flow cytometry. To assess their thrombin-generating capacity, MP were reconstituted in normal plasma. The coagulation activation status in vivo was quantified by plasma prothrombin fragment F1+2- and thrombin-antithrombin (TAT) measurements. Results. Annexin V-positive MP in the patients originated predominantly from platelets (PMP), and to a lesser extent from erythrocytes, endothelial cells (EMP) and granulocytes (GMP). Compared to healthy controls, the numbers of annexin V-positive PMP and TF-exposing MP were decreased (p = <0.001 for both), EMP were decreased (E-selectin, p = 0.003) or found equal (CD144, p = 0.063), erythrocyte-derived MP were equal (p = 0.726), and GMP were increased (p = 0.008). GMP numbers correlated with plasma concentrations of elastase (r = 0.70, p = 0.036), but not with C-reactive-protein or interleukin-6 concentrations. Patient samples also contained reduced numbers of annexin V-negative PMP, and increased numbers of erythrocyte-derived MP and GMP (p = 0.005, p = 0.021 and p <0.001, respectively). Patient MP triggered thrombin formation, which was reduced compared to the healthy controls (p = 0.008) and strongly inhibited by an anti-factor XII MoAb (two patients), by anti-factor XI MoAb (eight patients) or by anti-TF MoAb (four patients). Concentrations of F1+2 and TAT were elevated (p = 0.005 and p = 0.001, respectively) and correlated inversely with the number of circulating MP (and r = –0.51, p = 0.013, and r = –0.65, p = 0.001, respectively) and their thrombin generation capacity (F1+2: r = –0.62, p = 0.013). Conclusions. In patients with MODS and sepsis relatively low numbers of MP are present that differ from controls in their cellular origin, numbers and coagulation activation mechanisms.

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