scholarly journals Early complementopathy predicts the outcomes of patients with trauma

2019 ◽  
Vol 4 (1) ◽  
pp. e000217 ◽  
Author(s):  
Yansong Li ◽  
Qingwei Zhao ◽  
Bin Liu ◽  
Alexander Dixon ◽  
Leopoldo Cancio ◽  
...  
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Injury Severity ◽  
Burn Injury ◽  
Blunt Injury ◽  
Blood Levels ◽  
Classical Pathway ◽  
Trauma Patients ◽  
Burn Patients ◽  
Pathway Activation

BackgroundComplementopathy (rapid complement activation and consumption after trauma) has been reported in trauma patients, but the underlying mechanism of these phenomena and their clinical significance remain unclear. This study aimed to determine the complement/complement pathway activation and identify the association of complement activation with clinical outcomes in trauma patients.MethodsWe studied 33 trauma patients with mean Injury Severity Score of 25, and 25 healthy volunteers. Sera were collected on patients’ arrival at the emergency department, as well as 1, 2, 3, 5, and 7 days after trauma, to measure the levels of terminal complement activation product soluble C5b-9 (sC5b-9) by ELISA. In addition, the functional complement activation pathway was evaluated using a commercial complement system screening kit.ResultsSerum concentrations of sC5b-9 (complement terminal pathway activity) were significantly increased in trauma patients throughout the entire observation period except on day 1. Complement terminal activities were significantly higher in 27 of 33 patients with systemic inflammatory response syndrome (SIRS) than non-SIRS patients on day 2, day 5, and day 7. Increased serum levels of sC5b-9 positively correlated with SIRS. Functional complement analysis revealed that the classical pathway was the predominant pathway responsible for complement activation. Burn patients tended to have a greater and prolonged classical pathway activation than non-burn patients, and burn injury and blunt injury were associated with higher blood levels of sC5b-9 than penetrating injury.DiscussionEarly complement activation through the classical pathway after trauma is observed and positively correlated with the development of SIRS. Thus, monitoring of the complement system might be beneficial in the care of critically injured patients.Level of evidenceIII.Study typePrognostic.

scholarly journals Higher Mortality Rate in Moderate-to-Severe Thoracoabdominal Injury Patients with Admission Hyperglycemia Than Nondiabetic Normoglycemic Patients

2019 ◽  
Vol 16 (19) ◽  
pp. 3562
Author(s):  
Wei-Ti Su ◽  
Shao-Chun Wu ◽  
Sheng-En Chou ◽  
Chun-Ying Huang ◽  
Shiun-Yuan Hsu ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Injury Severity ◽  
Burn Injury ◽  
Past History ◽  
Trauma Patients ◽  
Thoracoabdominal Injuries ◽  
History Of ◽  
Level 1 ◽  
The Impact ◽  
Level 1 Trauma Center

Background: Hyperglycemia at admission is associated with an increase in worse outcomes in trauma patients. However, admission hyperglycemia is not only due to diabetic hyperglycemia (DH), but also stress-induced hyperglycemia (SIH). This study was designed to evaluate the mortality rates between adult moderate-to-severe thoracoabdominal injury patients with admission hyperglycemia as DH or SIH and in patients with nondiabetic normoglycemia (NDN) at a level 1 trauma center. Methods: Patients with a glucose level ≥200 mg/dL upon arrival at the hospital emergency department were diagnosed with admission hyperglycemia. Diabetes mellitus (DM) was diagnosed when patients had an admission glycohemoglobin A1c ≥6.5% or had a past history of DM. Admission hyperglycemia related to DH and SIH was diagnosed in patients with and without DM. Patients who had a thoracoabdominal Abbreviated Injury Scale score <3, a polytrauma, a burn injury and were below 20 years of age were excluded. A total of 52 patients with SIH, 79 patients with DH, and 621 patients with NDN were included from the registered trauma database between 1 January 2009, and 31 December 2018. To reduce the confounding effects of sex, age, comorbidities, and injury severity of patients in assessing the mortality rate, different 1:1 propensity score-matched patient populations were established to assess the impact of admission hyperglycemia (SIH or DH) vs. NDN, as well as SIH vs. DH, on the outcomes. Results: DH was significantly more frequent in older patients (61.4 ± 13.7 vs. 49.8 ± 17.2 years, p < 0.001) and in patients with higher incidences of preexisting hypertension (2.5% vs. 0.3%, p < 0.001) and congestive heart failure (3.8% vs. 1.9%, p = 0.014) than NDN. On the contrary, SIH had a higher injury severity score (median [Q1–Q3], 20 [15–22] vs. 13 [10–18], p < 0.001) than DH. In matched patient populations, patients with either SIH or DH had a significantly higher mortality rate than NDN patients (10.6% vs. 0.0%, p = 0.022, and 5.3% vs. 0.0%, p = 0.043, respectively). However, the mortality rate was insignificantly different between SIH and DH (11.4% vs. 8.6%, odds ratio, 1.4; 95% confidence interval, 0.29–6.66; p = 0.690). Conclusion: This study revealed that admission hyperglycemia in the patients with thoracoabdominal injuries had a higher mortality rate than NDN patients with or without adjusting the differences in patient’s age, sex, comorbidities, and injury severity.

Blood Transfusion is an Independent Predictor of Mortality after Blunt Trauma

2007 ◽  
Vol 73 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Anthony Charles ◽  
Almaasa Shaikh ◽  
Madonna Walters ◽  
Susan Huehl ◽  
Richard Pomerantz
Keyword(s):  
Logistic Regression ◽  
Blood Transfusion ◽  
Blunt Trauma ◽  
Injury Severity ◽  
Trauma Registry ◽  
Blunt Injury ◽  
Trauma Patients ◽  
Trauma Population ◽  
Transfusion Requirements ◽  
Level 2

Allogeneic blood transfusion is associated with increased morbidity and mortality. The authors evaluated the affect of blood transfusion, independent of injury severity on mortality. The authors conducted a retrospective review of all patients, age ≥18 years with blunt injury admitted to their Level 2 trauma center from 1994 to 2004 by query of the NTRACS trauma registry. Initial systolic blood pressure and heart rate determined the shock index. Logistic regression was used to model the affect of blood transfusion on mortality. Transfusion requirements were categorized as follows: A, 0 U; B, 1 to 2 U; C, 3 to 5 U; D, ≥6 U blood. In this sample of 8215 blunt trauma patients, 324 patients received blood transfusion. Mortality rates between the transfused and nontransfused groups were 15.12 per cent and 1.84 per cent ( P < 0.000) respectively. In the logistic regression model, transfusion category B did not have a significant affect on the odds of death ( P = 0.176); the affect of transfusing 3 to 5 U and ≥6 U had a mortality odds ratio of 3.22 ( P = 0.002) and 4.87 ( P = 0.000) respectively. Transfusing ≥2U blood was strongly associated with mortality in this blunt trauma population. There must be a continuous attempt to limit blood transfusion when feasible and physiologically appropriate.

scholarly journals Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway

2007 ◽  
Vol 82 (2) ◽  
pp. 817-827 ◽  
Author(s):  
Rheba S. Bonaparte ◽  
Pamela S. Hair ◽  
Deepa Banthia ◽  
Dawn M. Marshall ◽  
Kenji M. Cunnion ◽  
...  
Keyword(s):  
Immune Response ◽  
Coat Protein ◽  
Complement Activation ◽  
Health Concern ◽  
Classical Pathway ◽  
Serum Complement ◽  
Human Pathogens ◽  
Complement Activity ◽  
Pathway Activation ◽  
Human Astroviruses

ABSTRACT Human astroviruses (HAstVs) belong to a family of nonenveloped, icosahedral RNA viruses that cause noninflammatory gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified, with a worldwide distribution. While the HAstVs represent a significant public health concern, very little is known about the pathogenesis of and host immune response to these viruses. Here we demonstrate that HAstV type 1 (HAstV-1) virions, specifically the viral coat protein (CP), suppress the complement system, a fundamental component of the innate immune response in vertebrates. HAstV-1 virions and purified CP both suppress hemolytic complement activity. Hemolytic assays utilizing sera depleted of individual complement factors as well as adding back purified factors demonstrated that HAstV CP suppresses classical pathway activation at the first component, C1. HAstV-1 CP bound the A chain of C1q and inhibited serum complement activation, resulting in decreased C4b, iC3b, and terminal C5b-9 formation. Inhibition of complement activation was also demonstrated for HAstV serotypes 2 to 4, suggesting that this phenomenon is a general feature of these human pathogens. Since complement is a major contributor to the initiation and amplification of inflammation, the observed CP-mediated inhibition of complement activity may contribute to the lack of inflammation associated with astrovirus-induced gastroenteritis. Although diverse mechanisms of inhibition of complement activation have been described for many enveloped animal viruses, this is the first report of a nonenveloped icosahedral virus CP inhibiting classical pathway activation at C1.

scholarly journals Time-Dependent Activation of Complement system during Storage of Platelet Product

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4287-4287
Author(s):  
Jian Chen ◽  
Shangbin Yang ◽  
Spero R Cataland ◽  
Haifeng M Wu
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Research Funding ◽  
Storage Time ◽  
Adverse Reactions ◽  
Alternative Pathway ◽  
Pathway Activation ◽  
The Complement System ◽  
Transfusion Reactions

Abstract Platelet transfusion is known for carrying a high incidence of clinically significant transfusion reactions such as febrile nonhemolytic transfusion reaction. The mechanism responsible for these transfusion-associated adverse events, however, is poorly understood. In this study, we hypothesize that prolonged in vitro storage activates the complement system in the platelet product that in turn causes a high frequency of transfusion reactions. Fresh platelet units obtained from three blood donors were stored on a temperature controlled platelet rotator between 22-24 C°. An aliquot of platelet product was obtained using sterile techniques from each unit on day 2 through day 7. The platelet product from each collection was then immediately centrifuged to obtain platelet poor plasma for the study of complement activation levels. For all study samples, C4d levels were assayed to evaluate the activation of the classical pathway, factor Bb levels were measured to determine the status of the complement alternative pathway, C3a levels were used to examine common pathway activation, and C5a and C5b-9 were assayed for determination of the terminal pathway activation of the complement system. The reference range for each complement factor was determined using citrated plasma from 40 healthy donors. As shown in table 1, both C4d and C3a demonstrated time-dependent increases relevant to storage time. On day 7, C4d and C3a levels were five-fold higher than their baseline levels measured on day 2. In contrast, factor Bb levels remained stable and within the normal range throughout the study. Over a storage span of seven days, the terminal complement factors C5a and C5b-9 were also significantly increased, although not as dramatically as C4d and C3a. Figure 1 illustrates a progressive increase of C3 activation in all three study donors over the time of storage (2-7 days). This report, for the first time, provides strong evidence that substantial complement activation occurs in the platelet products under standard storage conditions. A longer storage time of platelet product in vitro is accompanied by a remarkable elevation of complement activation biomarkers. By examining the pattern of complement profiles in the stored platelets, we further demonstrated that the activation of the classic pathway, rather than alternative pathway, appears to be the driving event that leads up to a level of over-reactivity of the complement system. Given the fact that complement hyperactivation is known to disrupt host homeostasis and cause disease, the adverse reactions seen in platelet recipients is likely related to the infusion of C3a and C5a which are known to be potent inflammatory cytokines. The observations from this study therefore provide a new perspective in understanding the pathophysiology responsible for adverse reactions from platelet transfusions. Further studies will be required to fully evaluate the clinical impact of complement activation in transfused platelet products. Figure 1 Figure 1. Disclosures Cataland: Alexion Corporation: Honoraria, Research Funding, Speakers Bureau. Wu:Alexion Corporation: Honoraria, Research Funding, Speakers Bureau.

Extracorporeal membrane oxygenation in trauma: A single institution experience and review of the literature

2018 ◽  
Vol 41 (12) ◽  
pp. 845-853 ◽  
Author(s):  
Aaron Strumwasser ◽  
Joshua M Tobin ◽  
Reynold Henry ◽  
Chrissy Guidry ◽  
Caroline Park ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Trauma Patient ◽  
Patient Population ◽  
Injury Severity ◽  
Blunt Injury ◽  
Trauma Patients ◽  
Single Institution ◽  
Membrane Oxygenation ◽  
Severity Scores ◽  
Level I

Introduction: Limited options exist for cardiovascular support of the trauma patient in extremis. This patient population offers challenges that are often considered insurmountable. This article identifies a heterogeneous group of trauma patients in extremis who may benefit from extracorporeal membrane oxygenation. Methods: Data were sourced from the medical records of all patients placed on extracorporeal membrane oxygenation following trauma at a Level I Trauma Center between 1 December 2016 and 1 December 2017. Results: All patients were male (N = 7), mostly with blunt injuries (n = 5), with an average age of 41 years and with an average Injury Severity Scores of 33 (median = 34). Two out of seven patients survived (28.5%). Survivors tended to have a longer duration on extracorporeal membrane oxygenation (13.5 vs 3.8 days), had extracorporeal membrane oxygenation initiated later (15 vs 7.8 days), and had suffered a blunt injury. Two patients were initiated on veno-arterial extracorporeal membrane oxygenation (both non-survivors) and five were initiated on veno-venous extracorporeal membrane oxygenation (two survivors, three non-survivors). Five patients were heparinized immediately (one survivor, four non-survivors), and two patients were heparinized after clotting was noted in the circuit (one survivor, one non-survivor). Three of the seven (42.8%) patients suffered cardiac arrest either prior to, or during, the initiation of extracorporeal membrane oxygenation (all non-survivors). Discussion: Extracorporeal membrane oxygenation use in the trauma patient in extremis is not standard; however, this article demonstrates that extracorporeal membrane oxygenation is feasible in a complex, heterogeneous patient population when treated at designated centers.

Patients With Combined Thermal and Intraabdominal Injuries: More Salvageable Than Not

2020 ◽  
Vol 41 (4) ◽  
pp. 835-840
Author(s):  
Jaimie Chang ◽  
Emily Hejna ◽  
Chih-Yuan Fu ◽  
Francesco Bajani ◽  
Leah Tatabe ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Abdominal Surgery ◽  
Burn Injury ◽  
Multivariate Logistic Regression Analysis ◽  
Trauma Patients ◽  
Burn Patients ◽  
Severe Injuries ◽  
Abdominal Operation ◽  
Significant Difference ◽  
Intraabdominal Injury

Abstract This study aims to better characterize the course and outcome of the uncommon subset of trauma patients with combined thermal and intraabdominal organ injuries. The National Trauma Data Bank was queried for burn patients with intraabdominal injury treated in all U.S. trauma centers from July 1, 2011 to June 30, 2015. General demographics, Glasgow coma scale (GCS), shock index (SI), Abbreviated Injury Scale (AIS) for burn, Injury Severity Score (ISS), blood transfusions, and abdominal surgery were evaluated. During the 5-year study period, there were 334 burn patients with intraabdominal injury, 39 (13.2%) of which received abdominal surgery. Burn patients who underwent operations had more severe injuries reflected by higher SI, AIS, ISS, blood transfusion, and worse outcomes including higher mortality, longer hospital and ICU length of stay, and more ventilator days compared to patients who did not undergo an operation. Nonsurvivors also exhibited more severe injuries, and a higher proportion received abdominal operation compared to survivors. Multivariate logistic regression analysis revealed that GCS on arrival, SI, AIS, ISS, blood transfusion, and abdominal operation to be independent risk factors for mortality. Propensity score matching to control covariables (mean age, systolic blood pressure on arrival, GCS on arrival, SI, ISS, time to operation, blood transfusion, and comorbidities) showed that of trauma patients who received abdominal operation, those with concomitant burn injury exhibited a higher rate of complications but no significant difference in mortality compared to those without burns, suggesting that patients with concomitant burns are not less salvageable than nonburned trauma patients.

scholarly journals TUNABLE COMPLEMENT ACTIVATION BY PARTICLES WITH VARIABLE SIZE AND Fc DENSITY

Nano LIFE ◽  
2013 ◽  
Vol 03 (02) ◽  
pp. 1341001 ◽  
Author(s):  
PATRICIA M. PACHECO ◽  
BENJAMIN LE ◽  
DAVID WHITE ◽  
TODD SULCHEK
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
High Surface ◽  
Treatment Strategies ◽  
Surface Concentration ◽  
Engineered Nanoparticles ◽  
Classical Pathway ◽  
Highly Sensitive ◽  
And Control ◽  
The Complement System

The complement system is an integral innate immune component that is made up of a cascade of enzymatic proteins that, once activated, results in lysis of invading pathogens, opsonization or recruitment of other innate and/or acquired immune responders, or some combination of the three. Due to the importance of the signal amplification and control points present in the cascade, complement is highly sensitive to subtle variations in initiation conditions, including nanoscale changes to molecular spacing. Using Fc-functionalized microparticles and nanoparticles, we find that activation requires a minimum threshold surface concentration of Fc of at least 20% surface coverage. This result indicates that a high surface density Fc is necessary for micro/nanoparticle complement activation through the classical pathway. In addition, the magnitude of the response was dependent on the size of the particle, with larger particles causing decreased activation. We hypothesize that a high density of Fc is needed to efficiently bind and closely appose molecular initiators of the complement cascade, from initiation to terminal complement complex formation. These fundamental studies of the interaction of microparticles and nanoparticles with the immune system suggest design rules for particle size and molecular density that impact immunostimulation through the complement system. Providing a therapeutic agent to modulate the complement response could aid a variety of treatment strategies. Engineered nanoparticles with controlled gaps between molecular activators could lead to new types of immunomodulatory agents.

scholarly journals Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis

2001 ◽  
Vol 69 (12) ◽  
pp. 7304-7309 ◽  
Author(s):  
Ilhan Celik ◽  
Cordula Stover ◽  
Marina Botto ◽  
Steffen Thiel ◽  
Sotiria Tzima ◽  
...  
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Immune Defense ◽  
Classical Pathway ◽  
Complement Factor ◽  
Wild Type ◽  
Factor B ◽  
The Complement System ◽  
Deficient Mice

ABSTRACT The complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading microorganisms and activates complement via the classical pathway. Both defense systems cooperate within the innate immune response. We studied the role of the complement system in the host defense against experimental polymicrobial peritonitis using mice lacking either C1q or factor B and C2. The C1q-deficient mice lacked the classical pathway of complement activation. The factor B- and C2-deficient mice were known to lack the classical and alternative pathways, and we demonstrate here that these mice also lacked the lectin pathway of complement activation. Using inoculum doses adjusted to cause 42% mortality in the wild-type strain, none of the mice deficient in the three activation routes of complement (factor B and C2 deficient) survived (mortality of 100%). Mortality in mice deficient only in the classical pathway of complement activation (C1q deficient) was 83%. Application of further dilutions of the polymicrobial inoculum showed a dose-dependent decrease of mortality in wild-type controls, whereas no changes in mortality were observed in the two gene-targeted strains. These results demonstrate that the classical activation pathway is required for an effective antimicrobial immune defense in polymicrobial peritonitis and that, in the infection model used, the remaining antibody-independent complement activation routes (alternative and lectin pathways) provide a supporting line of defense to gain residual protection in classical pathway deficiency.

Effects of Covalent Functionalization on the Biocompatibility Characteristics of Multi-Walled Carbon Nanotubes

2008 ◽  
Vol 8 (5) ◽  
pp. 2347-2356 ◽  
Author(s):  
Carolina Salvador-Morales ◽  
Elena V. Basiuk ◽  
Vladimir A. Basiuk ◽  
Malcolm L. H. Green ◽  
Robert B. Sim
Keyword(s):  
Carbon Nanotubes ◽  
Chemical Modification ◽  
Human Plasma ◽  
Complement System ◽  
Complement Activation ◽  
Classical Pathway ◽  
Covalent Functionalization ◽  
Chemically Modified ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

We report the effect of chemical modification of multi-walled carbon nanotubes (MWNTs) on their activation of the human serum complement system, as well as the adsorption of human plasma proteins on MWNTs. Four different types of chemically-modified MWNTs were tested for complement activation via the classical and alternative pathways using haemolytic assays. Human plasma protein binding was also tested using an affinity chromatography technique based on carbon nanotube-Sepharose matrix. Covalent functionalization of MWNTs greatly altered the level of activation of the complement system via the classical pathway. For example, MWNTs functionalised with ε-caprolactam or L-alanine showed respectively >90% and >75% reduction in classical pathway activation compared with unmodified MWNTs. These results demonstrate for the first time that these types of chemical modification are able to alter considerably the levels of specific complement proteins bound by pristine MWNTs (used as a control experiment). The reduced levels of complement activation via the classical pathway, that are likely to increase biocompatibility, were directly correlated with the amount of C1q protein bound to chemically modified carbon nanotubes. An inverse correlation was also observed between the amount of complement factor H bound to chemically modified MWNTs and the level of complement consumption via the alternative pathway. Binding of human plasma and serum proteins to pristine and modified MWNTs was highly selective. The chemical modifications studied generally increased nanotube dispersibility in aqueous media, but diminished protein adsorption.

Natural Antibody and Complement Activation Characterize Patients with Idiopathic Nephrotic Syndrome

2021 ◽  
Author(s):  
Howard Trachtman ◽  
Jennifer Laskowski ◽  
Cameron Lee ◽  
Brandon Renner ◽  
Andrew Feemster ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Complement Activation ◽  
Minimal Change Disease ◽  
Idiopathic Nephrotic Syndrome ◽  
Classical Pathway ◽  
Glomerular Injury ◽  
Immune Mediated ◽  
Pathway Activation ◽  
Healthy Control ◽  
Natural Igm

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common forms of idiopathic nephrotic syndrome. The causes of these diseases are incompletely understood, but the response of patients to immunosuppressive therapies suggests that their pathogenesis is at least in part immune-mediated. Pre-clinical and clinical research indicates that activation of the classical pathway of complement contributes to glomerular injury in FSGS. Glomerular IgM deposits are also prominent in some patients, raising the possibility that IgM is a trigger of classical pathway activation. In the current study, we examined the pattern of complement activation in the glomeruli and plasma of patients with nephrotic syndrome. We also tested whether patients with FSGS and MCD have elevated levels of natural IgM reactive with epitopes on glomerular endothelial cells and cardiolipin. We found evidence of classical pathway activation in patients with idiopathic nephrotic syndrome compared to healthy control subjects. We also detected higher levels of self-reactive IgM to both targets. Based on these results, IgM and classical pathway activation may contribute to disease pathogensis in some patients with FSGS and MCD.

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