Background: Acute kidney injury (AKI) is common in the ICU and associated with morbidity and mortality.Markers of endothelial injury, including angiopoietin-2 (ang-2) and soluble thrombomodulin (sTM), are associated with AKI in sepsis.We sought to identify associations with risk for AKI after major trauma, where timing from injury to outcome can be accurately ascertained.Methods: We performed a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial, which compared 1:1:1 to 1:1:2 (plasma: platelets: RBC) transfusion ratios in severe trauma patients.We included patients with plasma collected at randomization who did not have AKI on presentation and did not die within 24 hours of presentation.Our primary outcome was AKI within 7 days of enrollment, defined as an increase from baseline of ≥ 0.3 mg/dL in 48 hours and/or ≥ 50% in serum creatinine in 7 days or need for new dialysis.Plasma biomarkers were log2 transformed, and relative-risk (RR) regression was performed to test associations between AKI and biomarker concentrations adjusting for age, sex, and injury severity score (ISS).We compared biomarkers between subjects with and without AKI at four time points (0 =h, 24h, 48h, and 72h) after randomization using a Mann-Whitney U test.Results: Among 464 participants, 91 (19.6%) developed AKI within 7 days of presentation (median onset 1.3 days), with similar rates between treatment arms (17% in 1:1:1 and to 22% in 1:1:2, p=0.13).Participants with AKI had higher ISS (32.93 vs. 26.4), received more blood products in total (31 vs.19 units), and had higher 30-day mortality (22% vs 9%).Doubling of sTM (adjusted RR = 1.96, 95% CI: 1.19 -3.24, p=0.008) and ang-2 (adjusted RR 1.35, 95% CI: 1.12 -1.62, p=0.002) on day 0 were associated with AKI.At 24 hours doubling of sTM (adjusted RR = 2.47, 95% CI: 1.90 -3.22, p <0.001) and ang-2 (adjusted RR 1.63, 95% CI: 1.42 -1.87, p<0.001) was significantly associated with AKI.In serially collected samples, concentrations of sTM and ang-2 at each timepoint were significantly higher in patients who developed AKI compared to patients who did not (Figure 1).Conclusions: Biomarkers of endovascular injury were significantly associated with AKI in patients with severe trauma.This analysis provides insight into the trajectories of these two biomarkers over the first 72 hours of critical illness and may help identify patients at increased risk for AKI early on in their presentation.

Previous studies have indicated that circulating factors play a significant role in muscle loss and impaired muscle recovery following burn injury. Additionally, it has been established that burn alters the overall lipid profile of WAT, but it has not been determined if burn can alter the signaling lipid profile in WAT. In response to burn injury, WAT undergoes a massive lipolysis, adipocyte size and lipid content are reduced, and the expression of several metabolic proteins, markers of innervation, and cytokines are altered. This study was to determine if burn injury instigates a remodeling of scWAT that causes metabolic dysfunction and secretion of novel lipids that function in an endocrine manner to increase skeletal muscle wasting in adult human subjects. Seven consented subjects were used for this study. All subjects had severe burn injury, 40-60% TBSA. Blood samples were collected prior to scheduled surgical procedures and subsequent plasma was used. We used MS/MS shotgun non-targeted lipidomics to determine the concentration of 112 species of oxidized lipids in the plasma. We identified 7 novel signaling lipids that were significantly increased in circulation, and 5 lipids that were significantly decreased in circulation within the first 48 h after burn injury in human subjects. The most striking increases were observed in 15-HETE and 15-oxoETE, arachidonic acid metabolites released from scWAT. Of these 7 lipids, 15-HETE was consistently significantly increased compared to normal samples throughout the first 7 days post-burn injury. Notably, it’s downstream metabolite, 15-oxoETE was also significantly increased in the circulation 4, 7, and 12 days post-burn injury. These exciting data indicate that burn injury significantly alters the lipidomic profile of scWAT. Future investigations will identify the physiological role for the increase in these lipids in response to burn injury. Determining signaling lipids will help in the clinical treatment of burn patients with severe burn.

Patients with burns less than 20% total body surface area (TBSA) make up the majority of burn admissions, yet there is minimal data in the literature pertaining to these patients. The purpose of this study was to analyze and identify the characteristics of patients with small burns with hospital length of stay (LOS) of one day in an attempt to reduce inappropriate admissions into the burn center. This was a retrospective cohort study of adult patients with less than 20% TBSA burns who were admitted to the burn unit over three years (2015-2017). Patients were stratified into two cohorts by LOS = 1 and LOS ≥ 2 days. Patients without a thermal injury, died within one day or underwent an operative procedure were excluded. The following variables were recorded and analyzed: demographics, TBSA, etiology and mechanism of injury, burn location, LOS, and mortality. Comorbidities such as hypertension, diabetes mellitus, seizure disorders, and psychiatric disorders were also recorded. The main outcome under study was LOS. Wilcoxon rank sum tests, Fishers’ exact test, and multivariable logistic regression were used to analyze the association of patient or injury characteristics and LOS. During the study period, there were 1007 admissions with 920 (91%) having burns < 20% TBSA of which 324 required an operative procedure and four others were excluded for other reasons. Thus, 592 patients met the inclusion criteria, 254 (42.9%) had a LOS of 1 day and 338 (57.1%) had a LOS ≥ 2 days. The median length of stay for those with LOS ≥ 2 days was 4 days (IQR 2, 7). There were no significant differences in age, BMI, or race between two groups. Males compromised 72% of the patients. In multivariable analysis, males had a lower probability for LOS beyond 1 day compared to females (OR=0.62, CI 95% [0.40-0.94], p=0.025). Psychiatric illness was the comorbidity with the strongest relationship for LOS (OR=1.90, CI 95% [1.20-3.03], p<0.001). Patients with LOS = 1 had a smaller percent TBSA, (2.5 (0, 15.5) vs. 5 (0.1, 19.0), p<0.001). TBSA was the predominant influencing factor on LOS beyond one day (OR=1.19 per 1% increment, CI 95% [1.12-1.25], p<0.001). Location of burn was found not to have a significant effect between the two cohorts. Of all admissions, 25% stayed for only one day. The multivariable analysis identified key factors that influence hospital LOS such as patients with LOS = 1 had a smaller percent TBSA and location of burn was found not to have a significant effect. Application of this study highlights the potential to reduce the health care burden and improve resource utilization by identifying patients requiring one day admission to the burn unit.

BACKGROUND Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model’s ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. METHODS The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. RESULTS Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. CONCLUSION Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated (“machine learning”) and thus could improve its predictive capability as additional data are accrued. LEVEL OF EVIDENCE Diagnostic test study/Prognostic study, level III.

Following severe thermal injuries, resuscitation with large volumes of isotonic, hypo-oncotic crystalloids has been widely used to maintain adequate tissue perfusion and blood pressure. However, after increases in morbidity and mortality were linked to over-resuscitation with crystalloid fluids, many surgeons began utilizing Fresh Frozen Plasma (FFP) for resuscitation. Use of FFP has been shown to decrease the amount of fluid needed overall while combatting fluid extravasation and systemic inflammation. The purpose of this project was to analyze the impact of FFP given to severely burned patients during the first 24 hours of resuscitation and its effects on resuscitation volumes and outcomes. A retrospective analysis was performed on patients admitted to a Hospital Burn Center between 01/2009 and 12/2016 with age ≥ 18 years, TBSA ≥ 20%, and a survival ≥ 24 hours post admission. Patients who received FFP during resuscitation were then propensity score matched to those who did not receive FFP. Univariate analyses were performed to compare groups. Twenty-eight patients who received FFP met inclusion criteria and were matched to 28 patients who did not receive FFP. The two groups did not differ significantly in gender, body weight, TBSA, % 3rd degree, and percent inhalation injury. When factoring in TBSA, patients who were given FFP received less fluid overall than those who were not given FFP [median 2.9 L/kg/TBSA (2.1, 3.7) versus 3.7 L/kg/TBSA (2.9, 4.7); p = 0.032]. While there was a trend towards higher mortality and incidences of acute respiratory failure (ARF) and sepsis in patients without FFP, this was not statistically significant. (TABLE) In severely burned patients, the use of FFP during resuscitation decreased the overall crystalloid requirements during the first 24 hours. A study with a higher number of patients is required to determine if this reduction in fluid results in reduced mortality, ARF, and sepsis. This study is important because it will help physicians determine which fluids should be administered to severe burn patients in order to decrease resuscitation volumes and improve outcomes.

Treatment and recovery of patients with severe traumatic injuries is impacted by an increase in metabolism. After burn injury, the ability to resume normal activities is compromised due to inactivity associated with bed rest as well as the catabolic response. Following discharge, a major goal is the ability to execute a long-term recovery plan. Previously we found daily exercise combined with SQ insulin improved body mass loss during the unloading period. The purpose of this study was to determine immediately following burn and disuse injury how a combination of daily resistance exercise and daily insulin injections during the unloading phase followed by daily resistance exercise during the reloading phase affects body and fat mass and food intake. Male, Sprague-Dawley rats were used. Injury was induced by a 40% TBSA burn injury and hindlimb unloaded immediately following injury. Rats were weight-matched into either saline vehicle (VEH; N=12) or insulin (INS; 5U/kg; N=12) for 14 days with daily resistance exercise. Daily resistance exercise was completed prior and following injury by adding weight to the tail during repetitive ladder climbing (5 climbs, 2X/days). Following removal from unloading at 14 days, rats were re-distributed within the original VEH or INS to exercise (EX; N=6) or no exercise (NEX; N=6) for 14 days. Body mass and food intake was collected daily throughout the study. Fat mass was collected at the end of the study. No differences in body mass were observed between any groups at the time of injury or day 14. Daily insulin showed a decrease in mean food intake over the last 5 days of the unloading phase with no differences in body mass. During the reloading phase, a steady increase in body mass was shown in all groups, however, INS, irrespective of exercise had a greater body mass increase. In addition, mean food intake was significantly increased in the INS + EX group during the reloading phase. Fat mass was not different between any of the groups. During the unloading phase, daily exercise with insulin elicited a decrease in food intake, however, the decrease in food intake did not result in differences between treatment groups in either body mass or fat mass, possibly showing additional mechanisms are causing overall metabolic changes. Possible metabolic changes during the reloading phase, indicate improvements may be occuring following removal from disuse. Different underlying factors seem to be influencing the acute metabolic changes offering possible opportunities for combinations of early interventions resulting in positive long-term outcomes. An exercise program may improve metabolic health following discharge.

The objectives of this study were to compare thromboelastography platelet mapping (TEG PM) with impedance aggregometry (Multiplate, MP) in a single trauma population and relate their results clinically.

Damage control laparotomy (DCL) is used widely in the management of patients with traumatic injuries but carries significant morbidity. Surgical‐site infection (SSI) also carries potential morbidity, increased costs and prolonged hospital stay. The aim of this study was to determine whether primary skin closure after DCL increases the risk of SSI.

Severe hyperfibrinolysis after trauma is a poorly understood phenomenon associated with profound shock, serious anatomic injuries, increased transfusions, and high mortality rates. Molecular mechanisms driving hyperfibrinolysis in trauma have not been completely delineated. The authors aimed to determine the relationship between severe hyperfibrinolysis and outcomes in trauma patients and characterize the role of the plasminogen activator (PA) system in this condition. A prospective observational study was performed in 163 adult level I trauma patients admitted between April and August 2012. Blood was collected on admission, and fibrinolysis was determined by plasmin-α2 antiplasmin (PAP) levels. Tissue-derived and urokinase PA (tPA and uPA, respectively), PA inhibitor (PAI-1), fibrinogen, and antithrombin levels were also measured. Patient demographics, vital signs, laboratory values, mechanisms and severity of injuries, transfusions, and outcomes were collected at admission or from patient records. Moderate fibrinolysis was defined as PAP level 1,500 to 20,000 μg/L and severe hyperfibrinolysis as PAP level more than 20,000 μg/L. Severe hyperfibrinolysis was observed in 10% of patients and associated with increased injury severity, greater transfusions, fewer ventilator and hospital-free days, and higher mortality. Plasmin-α2 antiplasmin level was directly correlated with tPA level and inversely correlated with PAI-1 level. Patients with both elevated tPA and reduced PAI-1 were more severely injured, received more transfusions, and experienced fewer ventilator and hospital-free days. In conclusion, Severe hyperfibrinolysis is observed in a small percentage of trauma patients and is associated with severe injuries, greater transfusions, and worse outcomes. This condition is mediated, in part, by excessive upregulation of profibrinolytic tPA in the absence of concomitant increases in antifibrinolytic PAI-1.

Fibrinogen is the first coagulation factor to reach critical levels during hemorrhage. Consequently, reestablishing normal fibrinogen levels is necessary for adequately achieving hemostasis. Fibrinogen is supplemented through administration of Fresh Frozen Plasma, cryoprecipitate, or Human Fibrinogen Concentrate RiaSTAP. RiaSTAP is most advantageous for fibrinogen replacement because it offers the highest fibrinogen concentration, the lowest volume, and the most accurate dose. Unfortunately, RiaSTAP is limited by a protocol reconstitution of 20 minutes. Therefore, physicians in emergency settings resort to a forceful and rapid reconstitution, which causes foaming and possible protein loss and/or damage. This study aims to address the in vitro effectiveness of protocol reconstituted RiaSTAP vs. rapidly reconstituted RiaSTAP® vs. thawed cryoprecipitate.

Smokers have higher levels of tissue factor, thrombin, and fibrinogen, potentially contributing to an increased risk of venous thromboembolism (VTE). We hypothesized that smokers admitted with major trauma would present with a hypercoagulable profile and be at increased risk for complications as a result. We also hypothesized that nicotine replacement therapy (NRT) would not affect short-term outcomes or mitigate hypercoagulability.

Conflicting data exists as to whether traumatic brain injury (TBI) is associated with coagulopathy measured with conventional coagulation testing (CCT). The purpose of this study was to evaluate the prevalence of coagulopathy in TBI patients and to assess where potential coagulation defects might exist by CCT and by rapid thrombelastography (r-TEG).

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by micro-computed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse.