scholarly journals Platelets differentially modulate CD4+ Treg activation via GPIIa/IIIb-, fibrinogen-, and PAR4-dependent pathways

Author(s):  
Matthias Bock ◽  
Christian B. Bergmann ◽  
Sonja Jung ◽  
Peter Biberthaler ◽  
Laura Heimann ◽  
...  

AbstractCD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.

2003 ◽  
Vol 285 (1) ◽  
pp. H47-H58 ◽  
Author(s):  
Jean White ◽  
James Thomas ◽  
David L. Maass ◽  
Jureta W. Horton

Early fluid resuscitation, antimicrobials, early excision, and grafting have improved survival in the early postburn period; however, a significant incidence of pneumonia-related sepsis occurs after burn injury, often progressing to multiple organ failure. Recent studies have suggested that this initial injury (burn injury) primes the subject, producing an exaggerated response to a second insult, such as pneumonia-related sepsis. We developed an experimental animal model that included a third-degree burn over 40% of the total body surface area, followed by sepsis (intratracheal administration of Streptococcus pneumoniae, 4 × 106 colony-forming unit), which was produced either 48 or 72 h after burn injury in adult male rats. Hearts harvested after either burn alone, sepsis alone, or burn plus sepsis were used to assess either contractile function (Langendorff) or cardiomyocyte secretion of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 (ELISA). Experimental groups included the following: 1) sham (sham burn and no sepsis); 2) burn injury alone studied either 24, 48, or 72 h postburn; 3) pneumonia-related sepsis in the absence of burn injury; and 4) pneumonia-induced sepsis studied either 48 or 72 h after an initial burn injury. Burn injury alone (24 h) or sepsis alone produced myocardial contractile defects and increases in pro- and anti-inflammatory cytokine secretion by cardiomyocytes. Sepsis that occurred 48 h postburn exacerbated the cardiac contractile defects seen with either burn alone or sepsis alone. Sepsis that occurred 72 h postburn produced contractile defects resembling those seen in either burn alone or sepsis alone. In conclusion, our data suggest that burn injury primes the subject such that a second insult early in the postburn period produces significantly greater cardiac abnormalities than those seen with either burn alone or sepsis alone.


Author(s):  
John A. M. Paro ◽  
Geoffrey C. Gurtner

Burn injury represents a complex clinical entity with significant associated morbidity and remains the second leading cause of trauma-related death. An understanding of the local and systemic pathophysiology of burns has led to significant improvements in mortality. Thermal insult results in coagulative necrosis of the skin and the depth or degree of injury is classified according to the skin layers involved. First-degree burns involve only epidermis and heal quickly with no scar. Second-degree burns are further classified into superficial partial thickness or deep partial thickness depending on the level of dermal involvement. Damage in a third-degree burn extends to subcutaneous fat. There is a substantial hypermetabolic response to severe burn, resulting in significant catabolism and untoward effects on the immune, gastrointestinal, and renal systems. Accurate assessment of the extent of burn injury is critical for prognosis and initiation of resuscitation. Burn size, measured in total body surface area, can be quickly estimated using the rule of nines or palmar method. A more detailed sizing system is recommended once the patient has been triaged. Appropriate diagnosis of burn depth will be important for later management. First-degree burns are erythematous and painful, like a sunburn; third-degree burns are leathery and insensate. Differentiating between second-degree burn types remains difficult. There are a number of formalized criteria during assessment that should prompt transfer to a burn centre.


2021 ◽  
Vol 10 (3) ◽  
pp. 476
Author(s):  
Ioana Tichil ◽  
Samara Rosenblum ◽  
Eldho Paul ◽  
Heather Cleland

Objective: To determine blood transfusion practices, risk factors, and outcomes associated with the use of blood products in the setting of the acute management of burn patients at the Victorian Adult Burn Service. Background: Patients with burn injuries have variable transfusion requirements, based on a multitude of factors. We reviewed all acute admissions to the Victorian Adult Burns Service (VABS) between 2011 and 2017: 1636 patients in total, of whom 948 had surgery and were the focus of our analysis. Method and results: Patient demographics, surgical management, transfusion details, and outcome parameters were collected and analyzed. A total of 175 patients out of the 948 who had surgery also had a blood transfusion, while 52% of transfusions occurred in the perioperative period. The median trigger haemoglobin in perioperative was 80mg/dL (IQR = 76–84.9 mg/dL), and in the non-perioperative setting was 77 mg/dL (IQR = 71.61–80.84 mg/dL). Age, gender, % total body surface area (TBSA) burn, number of surgeries, and intensive care unit and hospital length of stay were associated with transfusion. Conclusions: The use of blood transfusions is an essential component of the surgical management of major burns. As observed in our study, half of these transfusions are related to surgical procedures and may be influenced by the employment of blood conserving strategies. Furthermore, transfusion trigger levels in stable patients may be amenable to review and reduction. Risk adjusted analysis can support the implementation of blood transfusion as a useful quality indicator in burn care.


2017 ◽  
Vol 5 ◽  
Author(s):  
Kathleen S. Romanowski ◽  
Tina L. Palmieri

Abstract Burn injury is a leading cause of unintentional death and injury in children, with the majority being minor (less than 10%). However, a significant number of children sustain burns greater than 15% total body surface area (TBSA), leading to the initiation of the systemic inflammatory response syndrome. These patients require IV fluid resuscitation to prevent burn shock and death. Prompt resuscitation is critical in pediatric patients due to their small circulating blood volumes. Delays in resuscitation can result in increased complications and increased mortality. The basic principles of resuscitation are the same in adults and children, with several key differences. The unique physiologic needs of children must be adequately addressed during resuscitation to optimize outcomes. In this review, we will discuss the history of fluid resuscitation, current resuscitation practices, and future directions of resuscitation for the pediatric burn population.


2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 11-15 ◽  
Author(s):  
Tina L Palmieri ◽  
James H Holmes ◽  
Brett Arnoldo ◽  
Michael Peck ◽  
Amalia Cochran ◽  
...  

Abstract Objectives Studies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20–59% TBSA) burn using a restrictive or a liberal blood transfusion strategy. Methods Patients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin <7 g/dL) or liberal (transfuse hemoglobin <10 g/dL) strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. Results Three hundred and forty-five patients received 7,054 units blood, 2,886 in massive and 4,168 in restrictive. Patients were similar in age, TBSA, and inhalation injury. The restrictive group received less blood (45.57 ± 47.63 vs. 77.16 ± 55.0, p < 0.03 massive; 11.0 ± 16.70 vs. 16.78 ± 17.39, p < 0.001) major). In massive burn, the restrictive group had fewer ventilator days (p < 0.05). Median ICU days and LOS were lower in the restrictive group; wound healing, mortality, and infection did not differ. No significant outcome differences occurred in the major (20–59%) group (p > 0.05). Conclusions: A restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.


2017 ◽  
Vol 28 (1) ◽  
pp. 41
Author(s):  
Alia E. Al-Ubadi

Association between Procalcitonin (PCT) and C-reactive protein (CRP) and burn injury was evaluated in 80 burned patients from Al-Kindy and Imam Ali hospitals in Baghdad-Iraq. Patients were divided into two groups, survivor group 56 (70%) and non-survivor group 24 (30%). PCT was estimated using (Human Procalcitonin ELISA kit) provided by RayBio/USA while CRP was performed using a latex agglutination kit from Chromatest (Spain). Our results declared that the mean of Total Body Surface Area (TBSA %) affected were 63.5% range (36%–95%) in non-survivor patients, while 26.5% range (10%–70%) in survivor patients. There is a significant difference between the two groups (P = 0.00), the higher mean percentage of TBSA has a significant association with mortality. Serum PCT and CRP were measured at the three times of sampling (within the first 48hr following admission, after 5thdays and after 10th days). The mean of PCT serum concentrations in non-survivor group (2638 ± 3013pg/ml) were higher than that of survivor group (588 ± 364pg/ml). Significantly high levels of CRP were found between the survivor and non-survivor groups especially in the 10th day of admission P=0.000, present study show that significant differences is found within the non-survivor group through the three times P= 0.01, while results were near to significant differences within survivor group through the three times (P= 0.05).


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9984
Author(s):  
Shin-Yi Tsai ◽  
Chon-Fu Lio ◽  
Shou-Chuan Shih ◽  
Cheng-Jui Lin ◽  
Yu-Tien Chen ◽  
...  

Background Acute kidney injury (AKI) is one of the most severe complications of burn injury. AKI with severe burn injury causes high mortality. This study aims to investigate the incidence of and predisposing factors for AKI in burn patients. Methods This is a single-center, retrospective, descriptive criterion standard study conducted from June 27, 2015, to March 8, 2016. We used Kidney Disease Improving Global Outcomes criteria to define and select patients with AKI. The study was conducted by recruiting in hospital patients who suffered from the flammable cornstarch-based powder explosion and were treated under primary care procedures. A total of 49 patients who suffered from flammable dust explosion-related burn injury were enrolled and admitted on June 27, 2015. The patients with more than 20% total body surface area of burn were transferred to the intensive care unit. Patients received fluid resuscitation in the first 24 hours based on the Parkland formula. The primary measurements were the incidence of and predisposing factors for AKI in these patients. Demographic characteristics, laboratory data, and inpatient outcomes were also evaluated. The incidence of AKI in this cohort was 61.2% (n = 30). The mortality rate was 2.0% (n = 1) during a 59-day follow-up period. The multivariate analysis revealed inhalation injury (adjusted OR = 22.0; 95% CI [1.4–358.2]) and meeting ≥3 American Burn Association (ABA) sepsis criteria (adjusted OR = 13.7; 95% CI [1.7–110.5]) as independent risk factors for early advanced AKI. Conclusions The incidence rate of AKI was higher in this cohort than in previous studies, possibly due to the flammable dust explosion-related burn injury. However, the mortality was lower than that expected. In clinical practice, indicators of inflammation, including ABA sepsis criteria may help in predicting the risk of AKI in patients with burn injury.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
Linda E Sousse ◽  
Amanda Staudt ◽  
Christopher VanFosson

Abstract Introduction One of the hallmarks of critical illness and trauma is that it triggers resorptive bone loss, as well as an increase in bone fractures and a reduction in bone density. Sustained markers of bone resorption, bone formation, and regulators of bone signaling pathways are linked to prolonged inflammatory activities and the prolonged deterioration of bone microstructure. The objective of this study is to evaluate the bone fracture rate of the U.S Military, non-U.S. Military, North Atlantic Treaty Organization (NATO) Military, local civilian, and Coalition Forces population in Operation Enduring Freedom and Operation Freedom’s Sentinel with burns from 2005 to 2018 using the Department of Defense Trauma Registry (DoDTR; n=28,707). Our hypothesis is that there is a direct relationship between burn injury severity and bone fracture rates. Methods Pearson’s correlation coefficient and scatterplots were used in this retrospective, observational study to demonstrate the correlation between total body surface area (TBSA) burn and number of fractures by anatomical location. Results Approximately 15,195 patients (age: 26 ± 10 years) in Role 2 and Role 3 treatment centers reported fractures. Of those patients, 351 suffered from burns with 632 anatomical fracture locations. Facial fractures were most prominent (16%), followed by foot (12%), skull (12%), tibia/fibula (11%), hand (11%), and ulna/radius (10%). There was no initial correlation between n increasing severity of TBSA burn and count of fracture locations (ρ=-0.03, p=0.8572). Conclusions There was no acute correlation between burn severity and bone fracture rates; however, further analyses are required to assess chronic post-burn fracture rates.


Author(s):  
Brandon T. Nokes ◽  
Ayan Sen

Burn injuries may cause morbidity and death, and patients may have widely variable presentations and outcomes. This chapter focuses on the critical care aspects of burn injury and management issues of burn and electrical injuries. Burns are classified according to the amount of total body surface area (TBSA) affected, the depth of burn, and the type of exposure associated with the burn. More specifically, burns can be chemical, electrical, or thermal. Burn severity is determined by the depth of involvement.


2019 ◽  
pp. 67-76
Author(s):  
Rowan Pritchard-Jones ◽  
Kayvan Shokrollahi

Assessment of total body surface area of a burn injured patient is a crucial step in managing burn injury. The chapter describes a number of techniques from using the size of the patient’s palm as an estimate of 1% to the gold standard Lund and Browder Chart. Key caveats are explained, copies of the charts included as well as the use of the CE certified app Mersey Burns.


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