scholarly journals Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Florian Uhle ◽  
Christoph Lichtenstern ◽  
Thorsten Brenner ◽  
Thomas Fleming ◽  
Christian Koch ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasma Concentrations ◽  
Surface Expression ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Hla Dr ◽  
Secondary Stage ◽  
Initial Activation ◽  
Molecular Patterns ◽  
Dying Cells

Background. Severe traumatization induces a complex pathophysiology, driven by the patient’s own immune system. The initial activation is a result of damage-associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. Methods. We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry. Results. High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. Conclusion. Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well-known secondary stage of impaired immune responsiveness in trauma patients.

scholarly journals Impaired Surface Expression of HLA-DR, TLR2, TLR4, and TLR9 in Ex Vivo-In Vitro Stimulated Monocytes from Severely Injured Trauma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
David Heftrig ◽  
Ramona Sturm ◽  
Elsie Oppermann ◽  
Kerstin Kontradowitz ◽  
Katrin Jurida ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Surface Expression ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Severely Injured ◽  
Tlr4 Expression ◽  
Inflammatory Conditions ◽  
Hla Dr ◽  
Stimulation Of

Objective. Trauma patients (TP) frequently develop an imbalanced immune response that often causes infectious postinjury complications. Monocytes show a diminished capability of both producing proinflammatory cytokines and antigen presentation after trauma. TLR2, TLR4, and TLR9 recognize pathogens and subsequently activate monocytes. While there are conflictive data about TLR2 and TLR4 expression after trauma, no studies about the expression of TLR2, TLR4, TLR9, and HLA-DR on monocytes from TP after their secondary ex vivo-in vitro “hit” have been reported.Methods/Results. Ex vivo-in vitro lipopolysaccharide- (LPS-) stimulated blood from TP showed diminished interleukin- (IL-) 1β-release in TP for five postinjury days compared to healthy volunteers (HV). The recovery was observed at day 5. In parallel, monocytes from TP showed an impaired capability of TLR2, TLR4, and TLR9 expression after secondary stimulation compared to HV, while the measurement of unstimulated samples showed significant reduction of TLR4 and TLR9 at ED. Furthermore, HLA-DR decreased after trauma and was even more profound by stimulation of monocytes. Ratio of monocytes to leukocytes was significantly increased at days 6 and 7 after trauma compared to HV.Conclusion. Impaired expression of TLRs and HLA-DR in acute inflammatory conditions may be responsible for the well-described monocyte paralysis after severe trauma.

scholarly journals Cell-free nuclear, but not mitochondrial, DNA concentrations correlate with the early host inflammatory response after severe trauma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Julie A. Stortz ◽  
Russell B. Hawkins ◽  
David C. Holden ◽  
Steven L. Raymond ◽  
Zhongkai Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Inflammatory Response ◽  
Nuclear Dna ◽  
Severe Trauma ◽  
Organ Injury ◽  
Trauma Patients ◽  
Chronic Critical Illness ◽  
Molecular Patterns ◽  
The Relationship

Abstract Severe blunt trauma is associated with an early ‘genomic storm’ which causes simultaneous up- and down-regulation of host protective immunity. Excessive inflammation can lead to organ injury. In the absence of infection, the inflammatory response is presumably driven by release of endogenous alarmins called danger-associated molecular patterns (DAMPs), which initiate immune responses through pattern-recognition receptors (PRR). Here we examined the relationship between concentrations of cell-free (cf) nuclear DNA (ncDNA) and mitochondrial DNA (mtDNA) within 24 hours post trauma with circulating leukocyte transcriptomics and plasma IL-6 concentrations, as well as the patients’ clinical trajectories. In 104 patients enrolled from two level-1 trauma centers, ncDNA and mtDNA concentrations were increased within 24 hours of severe trauma, but only ncDNA concentrations correlated with leukocyte gene expression and outcomes. Surprisingly, ncDNA, not mtDNA concentrations, were significantly elevated in trauma patients who developed chronic critical illness versus rapid clinical recovery. Plasma IL-6 and leukocyte transcriptomics were better predictors of outcomes than cfDNA levels. Although mtDNA and ncDNA are significantly increased in the immediate post-trauma period, the dramatic inflammatory and gene expression changes seen after severe trauma are only weakly correlated with ncDNA concentrations, and more importantly, mtDNA concentrations are not associated with adverse clinical trajectories.

scholarly journals Splenectomy is Associated with Altered Leukocyte Kinetics after Severe Trauma

2020 ◽  
Author(s):  
Michel Teuben ◽  
Arne Hollman ◽  
Taco J. Blokhuis ◽  
Roman Pfeifer ◽  
Roy Spijkerman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Liver Trauma ◽  
Trauma Patients ◽  
Severely Injured ◽  
Cellular Immune

Abstract Background Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma.Methods All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals.Results A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 hours, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. Conclusions This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

scholarly journals CYTOKINE REGULATION OF THE IMMUNE RESPONSE IN PATIENTS WITH ACUTE NECROTIC PANCREATITIS COMPLICATED BY MULTI-ORGANIC FAILURE

2020 ◽  
pp. 20-24
Author(s):  
V. P. Poliovy ◽  
O. V. Rotar ◽  
A. S. Palyanytsia ◽  
I. G. Chepega
Keyword(s):  
Immune Response ◽  
Organ Failure ◽  
Plasma Concentrations ◽  
Multiple Organ ◽  
Cytokine Regulation ◽  
Hla Dr ◽  
Necrotic Pancreatitis ◽  
Organic Failure ◽  
Complications And Mortality ◽  
Efficacy Of Treatment

Aim: To study the cytokine regulation of the immune response in patients with acute necrotic pancreatitis (ANP) complicated by multiple organ failure (MON). Material and methods: A prospective cohort study of 22 patients with ANP complicated by MON who were treated in the clinic during 2014-2020 has been performed. We studied changes in blood cells expressing clusters CDIIa +, CD162 +, CD95 +, CD16 +, HLA-DR + molecules, levels of interleukins IL-2, IL-4, IL-6. The efficacy of treatment was determined by the duration of the organ failure, the level of postoperative complications and mortality. Results: Low expression of CD11a + and CD162 + on immunocompetent cells together with two time reduction of the content of CD95 + cells was observed in patients with ANP complicated by MON, which caused a decrease in the concentration of IL-6 at the same time with a slight increase in IL-4. A permanent reduction of the content of CD11a+-, CD162+- and CD95+-leukocytes simultaneously with a drop of the concentration of IL-4 and an excessive increase in the levels of IL-2 and IL-6 was associated with a negative course of the disease. Conclusions: The imbalance of cytokine regulation of the immune response develops in patients with ANP, complicated by MON. Progressive and excessive increase of plasma concentrations of IL-2 and IL-6 occurs as well as complete absence of IL-4 occurs in patients with an adverse course of the disease.

scholarly journals Dynamics of cytokines in patients with enteral insufficiency in advanced peritonitis

2020 ◽  
Vol 24 (4 (96)) ◽  
pp. 85-92
Author(s):  
V. Polyovyj ◽  
O. Plehutsa ◽  
O. Dzigal ◽  
A. Palyanytsia ◽  
I. Chepega
Keyword(s):  
Immune Response ◽  
Plasma Concentrations ◽  
Early Postoperative Period ◽  
Cytokine Profile ◽  
Blood Levels ◽  
Control Parameters ◽  
Histocompatibility Complex ◽  
Laboratory Markers ◽  
Hla Dr ◽  
Comprehensive Examination

In this work, changes in the cytokine profile in patients with common forms of peritonitis with enteral insufficiency were studied. The obtained results were compared in patients who survived after surgery and programmed peritoneal sanation and patients who died in the early postoperative period. The aim of the study was to investigate the dynamics of cytokine profile of patients with common forms of peritonitis complicated by enteral insufficiency in order to determine their prognostic value. Material and methods. The object of the study was the blood of 23 patients with common forms of peritonitis and 17 healthy volunteers. To assess the condition of patients performed a dynamic determination in a comprehensive examination of laboratory markers of endogenous toxemia and systemic inflammatory response syndrome: immunological changes in patients by examining blood cells expressing clusters of CD11a+, CD162+, CD95+, CD16+, and molecules of the main histocompatibility complex HLA-DR+ and the level of interleukins IL-2, IL-4, IL-6. Results. During the study in patients with widespread peritonitis complicated by enteral insufficiency, at the time of hospitalization, there was a six-fold decrease in blood levels of CD11a+ cells and the content of CD162+ and CD16+ cells, respectively, 2,8 and 2 times, compared with healthy people. It has been shown that a single remediation programmed relaparotomy within two weeks effectively corrects these changes except for expression on CD16+ cells, which indicates a low effect of this type of surgery on the elimination of immune complexes. It was found that the concentration in plasma IL-2 increased 5 times and was 27,1% higher than that in almost healthy individuals. At the same time, the level of IL-4 in the blood decreased sharply – 4 times. Plasma IL-6 content also reduced. One week after relaparotomy, the expression of HLA-DR + molecules on immunocompetent cells increased again and was 1,8 times higher than the control parameters. In addition, the content of cytokines in the blood plasma increased sharply: the level of IL-2 exceeded the control by 2,4 times, IL-4 by 4 times, and IL-6 by 2 times. Conclusions. 1. Progressive and noticeable decrease in IL-2 content occurs in patients with widespread peritonitis complicated by enteral insufficiency in the complete absence of IL-4 in the blood on the background of a permanent and significant increase in plasma concentrations of IL-6. 2. Under conditions of suppression of the immune response, due to intoxication of the patient's body, the mechanism of endogenous inhibition of the immune response "IL-6 – corticoliberin – corticotropin – corticosteroids" is additionally realized.

scholarly journals Facts and Fiction: The Impact of Hypothermia on Molecular Mechanisms following Major Challenge

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Michael Frink ◽  
Sascha Flohé ◽  
Martijn van Griensven ◽  
Philipp Mommsen ◽  
Frank Hildebrand
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Severe Trauma ◽  
Accidental Hypothermia ◽  
Induced Hypothermia ◽  
Trauma Patients ◽  
Protective Effects ◽  
Elective Cardiac Surgery ◽  
The Impact

Numerous multiple trauma and surgical patients suffer from accidental hypothermia. While induced hypothermia is commonly used in elective cardiac surgery due to its protective effects, accidental hypothermia is associated with increased posttraumatic complications and even mortality in severely injured patients. This paper focuses on protective molecular mechanisms of hypothermia on apoptosis and the posttraumatic immune response. Although information regarding severe trauma is limited, there is evidence that induced hypothermia may have beneficial effects on the posttraumatic immune response as well as apoptosis in animal studies and certain clinical situations. However, more profound knowledge of mechanisms is necessary before randomized clinical trials in trauma patients can be initiated.

scholarly journals Splenectomy is associated with altered leukocyte kinetics after severe trauma

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Michel Paul Johan Teuben ◽  
Arne Hollman ◽  
Taco Blokhuis ◽  
Roman Pfeifer ◽  
Roy Spijkerman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Liver Trauma ◽  
Trauma Patients ◽  
Severely Injured ◽  
Cellular Immune

Abstract Background Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma. Methods All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals. Results A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. Conclusions This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

scholarly journals Cost-effectiveness of a hybrid emergency room system for severe trauma: a health technology assessment from the perspective of the third-party payer in Japan

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takahiro Kinoshita ◽  
Kensuke Moriwaki ◽  
Nao Hanaki ◽  
Tetsuhisa Kitamura ◽  
Kazuma Yamakawa ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Emergency Room ◽  
Healthcare Costs ◽  
Cost Effective ◽  
Severe Trauma ◽  
Third Party ◽  
Trauma Patients ◽  
Short Term ◽  
The Third

Abstract Background Hybrid emergency room (ER) systems, consisting of an angiography-computed tomography (CT) machine in a trauma resuscitation room, are reported to be effective for reducing death from exsanguination in trauma patients. We aimed to investigate the cost-effectiveness of a hybrid ER system in severe trauma patients without severe traumatic brain injury (TBI). Methods We conducted a cost-utility analysis comparing the hybrid ER system to the conventional ER system from the perspective of the third-party healthcare payer in Japan. A short-term decision tree and a long-term Markov model using a lifetime time horizon were constructed to estimate quality-adjusted life years (QALYs) and associated lifetime healthcare costs. Short-term mortality and healthcare costs were derived from medical records and claims data in a tertiary care hospital with a hybrid ER. Long-term mortality and utilities were extrapolated from the literature. The willingness-to-pay threshold was set at $47,619 per QALY gained and the discount rate was 2%. Deterministic and probabilistic sensitivity analyses were conducted. Results The hybrid ER system was associated with a gain of 1.03 QALYs and an increment of $33,591 lifetime costs compared to the conventional ER system, resulting in an ICER of $32,522 per QALY gained. The ICER was lower than the willingness-to-pay threshold if the odds ratio of 28-day mortality was < 0.66. Probabilistic sensitivity analysis indicated that the hybrid ER system was cost-effective with a 79.3% probability. Conclusion The present study suggested that the hybrid ER system is a likely cost-effective strategy for treating severe trauma patients without severe TBI.

Splanchnic Hypoperfusion-Directed Therapies in Trauma: A Prospective, Randomized Trial

2005 ◽  
Vol 71 (3) ◽  
pp. 252-260 ◽  
Author(s):  
Stephen M. Cohn ◽  
Stephen M. Cohn ◽  
Orlando Kirton ◽  
Margaret Brown ◽  
S. Morad Hameed ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Injury Severity ◽  
Ischemia Reperfusion ◽  
Unit Group ◽  
Severe Trauma ◽  
Prospective Randomized Trial ◽  
Gastric Tonometry ◽  
Trauma Patients ◽  
Splanchnic Perfusion ◽  
Splanchnic Hypoperfusion

Splanchnic hypoperfusion as reflected by gastric intramucosal acidosis has been recognized as an important determinant of outcome in shock. A comprehensive splanchnic hypoperfusion-ischemia reperfusion (IRP) protocol was evaluated against conventional shock management protocols in critical trauma patients. The study was a prospective randomized trial comparing three therapeutic approaches to hypoperfusion after severe trauma in 151 trauma patients admitted to the intensive care unit. Group 1 patients received hemodynamic support based on conventional indicators of hypoperfusion. In group 2, resuscitation was further guided by gastric tonometry-derived estimates of splanchnic hypoperfusion and included more invasive hemodynamic monitoring and additional administration of colloid or crystalloid solutions, or inotropic support. Group 3 patients additionally received therapies specifically aimed at optimizing splanchnic perfusion and minimizing oxidant-mediated damage from reperfusion. The three groups were similar based on age, Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II Scores. There were no statistically significant differences in mortality rates, organ dysfunction, ventilator days, or length of stay between any of the interventions. Techniques of optimization of splanchnic perfusion and minimization of oxidant-mediated reperfusion injury evaluated in this study were not advantageous relative to standard resuscitation measures guided by conventional or tonometric measures of hypoperfusion in the therapy of occult and clinical shock in trauma patients.

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