Innate Immune System Response to Burn Damage—Focus on Cytokine Alteration

In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient’s innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.

The effect of hyperoxia on the hemostasiological status of severely burned patients

The state of the hemostasis system was studied in 9 patients of the middle age group (44 ± 9.94 years) who received thermal trauma on an area of more than 32% (49.4 ± 18.3) of the body surface, accompanied by the development of burn shock. The standard therapy for burn injury was supplemented with HBO sessions. Treatment with hyperbaric oxygen was carried out in pressure chambers BLKS-307, BLKS-307/1. The state of the coagulation, anticoagulant and fibrinolytic links of the hemostasis system, as well as the viscoelastic properties of the blood, were assessed immediately before the HBO session and immediately after it. The total number of comparison pairs was 45. Under the influence of HBO therapy, there was an increase in the activity of antithrombin III (ATIII), protein C (PrS) and a decrease in the viscoelastic properties of blood (p <0.05). Positive deviations in the values of ATIII, Pr C, von Willebrand factor, APTT, prothrombin and thrombin time, fibrinogen, factor XIII, XIIa-dependent fibrinolysis, D-dimers and thromboelastography parameters were revealed. The maximum frequency of their occurrence was recorded for ATIII (95%), the minimum - for the D-dimer (62%). After HBO procedures, undesirable deviations of the hemostatic system parameters were also noted. They were chaotic, were compensated by an increase in the activity of physiological anticoagulants and were not accompanied by complications of a thrombogenic nature. Thus, conducting HBO therapy sessions in the acute period of burn disease increases the activity of physiological anticoagulants and stabilizes the viscoelastic properties of blood. There is a high frequency of occurrence of positive effects of hyperoxia on the components of the hemostasis system. The identification of its undesirable effects indicates the need to monitor the state of the hemostasis system during HBO procedures.

Initial Results of the American Burn Association (ABA) Observational Multi-Center Evaluation on the Effectiveness of the Burn Navigator

The objective of this multi-center observational study was to evaluate resuscitation volumes and outcomes of patients who underwent fluid resuscitation utilizing the Burn Navigator (BN), a resuscitation clinical decision support tool. Two analyses were performed: examination of the first 24 hours of resuscitation, and the first 24 hours post-burn regardless of when the resuscitation began, to account for patients who presented in a delayed fashion. Patients were classified as having followed the BN (FBN) if all hourly fluid rates were within ±20 mL of BN recommendations for that hour at least 83% of the time, otherwise they were classified as not having followed BN (NFBN). Analysis of resuscitation volumes for FBN patients in the first 24 hours resulted in average volumes for primary crystalloid) and total fluids administered of 4.07 ± 1.76 mL/kg/TBSA (151.48 ± 77.46 mL/kg), and 4.68 ± 2.06 mL/kg/TBSA (175.01 ± 92.22 mL/kg), respectively. Patients who presented in a delayed fashion revealed average volumes for primary and total fluids of 5.28 ± 2.54 mL/kg/TBSA (201.11 ± 106.53 mL/kg), 6.35 ± 2.95 mL/kg/TBSA (244.08 ± 133.5 mL/kg), respectively. There was a significant decrease in the incidence of burn shock in the FBN group (p&lt; 0.05). This study shows that the BN provides comparable resuscitation volumes of primary crystalloid fluid to the Parkland Formula, recommends total fluid infusion less than the Ivy Index, and was associated with a decreased incidence of burn shock. Early initiation of the BN device resulted in lower overall fluid volumes.

WAYS FOR IMPROVING THE RESULTS OF TREATMENT OF VICTIMS WITH DEEP ELECTRICAL BURNS

Aim. improving the results of treatment of victims with electrical injury, through early diagnosis of the depth and extent of the lesion and the introduction of methods of active surgical tactics.Material and methods. We examined 674 patients with electrical injuries admitted to the RSCEMP in the period from 2001 to 2017. the patients used the methods of bilateral comparative dermal thermometry and X-ray densitometry. To assess the severity of burn shock, the indicators of central and peripheral hemodynamics, blood oxygenation, Frank’s index, thermometry and neutrophil-lymphocyte index were assessed. The calculation of statistical indicators was carried out using the Microsoft Excel 2010 software package, including built-in statistical processing functions. The significance of differences between the groups in the quantitative values of the parameters was determined by the Student’s test. Statistical indicators were considered reliable, with p <0.05. Results. It was found that the temperature difference in the armpit and the first interdigital space of the foot by 0.5-1.5 ° C corresponds to a mild degree of burn shock, and in severe and extremely severe burn shock, the temperature difference in these zones was 1.6 -4 ° С and above 4 ° С. It is noted that active surgical tactics by early fasciotomy on the first day of injury and early necrectomy contributes to a significant decrease in the frequency of amputation and disarticulation of the extremities from 55.8 to 9.8%, makes it possible to perform early autodermoplasty, improves the survival rate of autografts and shortens the period of inpatient treatment. Active surgical tactics contributed to an improvement in the engraftability of autografts (95.2% versus 87.4%), a 2.6-fold decrease in the frequency of repeated autodermoplasty at sites of non-engraftment, a significant decrease in the frequency of mutilation operations (amputation and disarticulation of the extremities) and a reduction in the duration of inpatient treatment with 41.1 ± 12.3 to 37.7 ± 10.4 days. Conclusions. Early fasciotomy on the first day of injury and early necrectomy contribute to a significant decrease in the frequency of amputation and disarticulation of the extremities from 55.8 to 9.8%, make it possible to perform autodermoplasty in the shortest possible time and reduce the time of inpatient treatment. The process of osteonecrosis is completed within 2 weeks after the injury, and by this time it is possible to start osteonecrectomy, including one-stage radical osteonecrectomy over the entire surface of osteonecrosis.

Cerium(III) Nitrate Containing Electrospun Wound Dressing for Mitigating Burn Severity

Thermal injuries pose a risk for service members in prolonged field care (PFC) situations or to civilians in levels of lower care. Without access to prompt surgical intervention and treatment, potentially salvageable tissues are compromised, resulting in increases in both wound size and depth. Immediate debridement of necrotic tissue enhances survivability and mitigates the risks of burn shock, multiple organ failure, and infection. However, due to the difficulty of surgical removal of the burn eschar in PFC situations and lower levels of care, it is of utmost importance to develop alternative methods for burn stabilization. Studies have indicated that cerium(III) nitrate may be used to prolong the time before surgical intervention is required. The objective of this study was to incorporate cerium(III) nitrate into an electrospun dressing that could provide burst release. Select dosages of cerium(III) nitrate were dissolved with either pure solvent or polyethylene oxide (PEO) for coaxial or traditional electrospinning set-ups, respectively. The solutions were coaxially electrospun onto a rotating mandrel, resulting in a combined nonwoven mesh, and then compared to traditionally spun solutions. Dressings were evaluated for topography, morphology, and porosity using scanning electron microscopy and helium pycnometry. Additionally, cerium(III) loading efficiency, release rates, and cytocompatibility were evaluated in both static and dynamic environments. Imaging showed randomly aligned polymer nanofibers with fiber diameters of 1161 ± 210 nm and 1090 ± 250 nm for traditionally and coaxially spun PEO/cerium(III) nitrate dressings, respectively. Assay results indicated that the electrospun dressings contained cerium(III) nitrate properties, with the coaxially spun dressings containing 33% more cerium(III) nitrate than their traditionally spun counterparts. Finally, release studies revealed that PEO-based dressings released the entirety of their contents within the first hour with no detrimental cytocompatibility effects for coaxially-spun dressings. The study herein shows the successful incorporation of cerium(III) nitrate into an electrospun dressing.

Impact of Fluid Resuscitation Regimes in Relative Risk of Mortality in Burned Patients

Background; Some studies have supported the opinion that patients who get greater volumes of resuscitation fluids are at a higher chance of edema, complications, and probably bad outcomes. In the results of the International Society of Burn Injuries approximately half (49.5%) added colloid before 24h. This study aims to analyze the relative risk for mortality comparing resuscitation in the first 24 hours with Parkland and resuscitation with the use of Colloids. Material and Methods; This was an observational prospective cohort study conducted in the Service of Burns of the University Hospital Centre "Mother Teresa" in Tirana (UHCT), Albania. The study includes adult patients with critical burns > 40% TBSA, hospitalized in the Intensive Care Unit of the service during the period 2014 to 2019. Resuscitation in the first 24 hours is done with Ringer Lactate according to Parkland and with Ringer Lactate with the addition of colloids after 12 hours. Results; The data for organ dysfunction and organ insufficiency were the same in the two groups without statistical significance. Mortality in the RL group was 48% (24 deaths of 50 patients) while in the RL + Colloid rehydrated group was 46% (23 deaths of 50 patients). Patients which have 40-60% burns and are rehydrated with RL + Colloids have a risk of death 0.4 times less than those rehydrated with RL. Conclusions; Resuscitation with Ringer lactate and Colloids in the first 24 hours of thermal damage is a rehydration alternative for the treatment of burn shock. This therapy especially helps patients with major burns > 40% TBSA who during rehydration require large amounts of fluids and are associated with severe plasma hypoalbuminemia. Number Need to Treat (NNT benefit) is 10 so 1 in 10 patients can benefit in lowering the risk of death with RL + Colloid rehydration.

Measures of Risk for Sepsis and Mortality in Severe Burned Patients with Stress Induced Hyperglycemia.

Background; Hyperglycemia as a medical condition due to diabetes or other underlying conditions like Stress-Induced Hyperglycemia and sepsis as a life-threatening medical condition are two of the challenges faced during burn treatment. The purpose of this study was to evaluate the risk for sepsis and mortality for the patients with critical hyperglycemic values during the disease. Material and Methods; This is an observational retrospective cohort study conducted in the Service of Burns of the University Hospital Centre “Mother Teresa” in Tirana (UHCT), Albania from 1st January 2010 to 31st December 2014. Patients were categorized as having euglycemia (mean BG values ranging from 80-120 mg/dl), moderate hyper Sepsis was defined according to the ABA Consensus Panel Publication for Infection and Sepsis glycemia (mean BG values <180 mg/dl) or critical hyperglycemia (mean BG values ≥180 mg/dl). to evaluate the impact of the presence of critical hyperglycemia during the disease in sepsis and mortality, we performed Relative risk, Odds ratio Results; Those who had overall hyperglycemia (Moderate and Critical) had 2.6 times the risk for sepsis compared to those who were in the euglycemia group. Analyzing the risk of mortality in patients with overall hyperglycemia during the disease, we observed that the chance of a bad outcome was 2.7 times more likely to occur if the patient had hyperglycemia (RR=2.7). Conclusions: Glucose values on admission, as one of the derangement features of burn shock, are prognostic factors in critical hyperglycemia during burn disease and have a close relationship with other outcomes (sepsis and mortality).

127 Plasma from Patients with Burn Injury Increases Endothelial Permeability In-Vitro

Introduction The contribution of endothelial injury to the pathogenesis of burn shock is not well characterized. Human umbilical endothelial cells (HUVECs) have been used to study endotheliopathy in myriad shock states. This work investigates the impact of burn patient plasma on the vascular endothelium and its barrier function. Methods HUVECs were seeded into the apical chambers of transwell plates and cultured over 5–7 days to a confluent monolayer which was confirmed by a transendothelial electrical resistance (TEER) of ≥30Ω. After IRB approval, plasma was collected from burn-injured patients 4 hours after admission. Demographic and injury characteristics were collected from the medical record. Plasma Syndecan-1 (SDC-1) was quantified by ELISA. HUVEC monolayers were exposed to 10% multi-donor pooled healthy human plasma (HHP) or burn patient plasma. Monolayers were subsequently incubated with FIT-C Dextran (40,000 kD). FIT-C diffusion through monolayers was measured in basal chamber supernatants. Monolayer permeability was measured with indices calculated by normalizing values to blank (transwell inserts) and HHP-treated monolayer FIT-C diffusion. HUVECs were also cultured on glass slides and exposed to HHP or burn patient plasma. Cells were fixed with 4% Paraformaldehyde and F-Actin was stained with Texas Red-Phalloidin. Intercellular gap area was calculated using imaging software. Differences between treatment conditions were analyzed with Welch’s t-test and one-way ANOVA, simple linear regression was used to characterize the relationship between plasma SDC-1 and permeability indices, significance was set at p &lt; 0.05. Results Eight burn patient plasma samples were tested. Patients were mostly male (75%) with a mean age of 50±20 years and mean %TBSA burn of 37±34%. Five burn plasma samples significantly increased monolayer permeability. There were no significant differences between patient samples that increased permeability in age, TBSA, gender, or in-hospital mortality. Monolayer permeability indices increased between 7–15% (p&lt; 0.05) among burn plasma treatment conditions (n=6) that increased permeability. There was a strong relationship between monolayer permeability index (%) and plasma SDC-1 (µg/mL) (p=0.03, R2=0.93). Morphological F-actin rearrangement was apparent on microscopy and intercellular gap area was increased in burn plasma treatment conditions (12% vs. 49%, p≤0.0007, n=6). Conclusions Plasma from burn patients induces endothelial damage that increases endothelial cell monolayer permeability. The endothelial biomarker SDC-1 is a reliable indicator of endothelial damage. F-actin rearrangement and an increase in intercellular gap area likely contributes to burn endotheliopathy.

OPTIMIZATION OF INTENSIVE THERAPY FOR BURN SHOCK

The literature provides about 100 different definitions of the concept of shock(G. Bernard, 2001). A large number of definitions of the concept are directly dependent on the reasons that caused it. Burn shock is the first stage of burn disease and develops when the surface of the body is affected by an area of 10-15% for superficial and 5-10% for deep burns.This article discusses the optimization of intensive therapy for burn shock.Keywords:pathogenesis, stages of burns, treatment principles, Evans formula, criteria for recovery from shock