Temporal expression of circulating miRNA after severe injury.

BACKGROUND: Severe injury can lead to immune dysfunction and predispose patients to infection and death. Micro-RNAs regulate gene expression and may act as biomarkers for susceptibility to infection. The aim of this study was to examine the temporal and differential expression of previously identified dysregulated micro-RNAs in patients with severe injury. METHODS: Fourteen severely injured patients requiring transfusion were enrolled prospectively in this study approved by our institutional review board. Inclusion criteria consisted of adult patients deemed clinically to be in hemorrhagic shock necessitating transfusion in the acute phase of their injury care. Peripheral blood samples were obtained after admission to the surgical intensive care unit and again at 6, 12, 24, and 48 hours after admission. The samples obtained at arrival to the intensive care unit and 24 and 48 hours later were analyzed in this data set. Fourteen healthy volunteers served as controls. The 10 dysregulated micro-RNAs identified in a prior study at the 12-hour time point and important genes in innate immunity were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: The participants were 21-77 years old (median, 42), 78% were male, and their Injury Severity Score ranged from 11 to 43 (median, 27); 11 had blunt and 3 had penetrating injuries. Three were intubated and 5 had received blood products before arrival at the hospital. Base deficit on hospital admission was 3-20 (median, 9). All patients required blood transfusion secondary to blood loss sustained during injury. Eleven of the 14 patients went directly to the operating room from the emergency department for control of the source of hemorrhage. Survival to discharge was 93%. Seven patients developed infection. Compared with healthy controls, miR-106a was downregulated at all time points compared with controls (P < .05). miR-618 was upregulated in initial blood draws (P < .05) and at 24 and 48 hours (P < .06). Tumor necrosis factor α and human leukocyte antigen-DR (HLA-DR) were downregulated, and interleukin-10 and PD-L1 were upregulated (P < .05). In patients who developed infection, miR-106a levels appeared more downregulated than those who did not develop infection. CONCLUSION: miR-106a was downregulated in trauma patients after major injury for up to 48 hours after intensive care unit admission. Tumor necrosis factor α and interleukin-10 are targeted by miR-106a, which are regulators of the immune response. Manipulation of micro-RNA expression may be a therapeutic target for immune dysfunction.

Acute haemolysis, DIC and renal failure after transfusion of uncross-matched blood during trauma resuscitation: illustrative case and literature review.

AIMS/OBJECTIVES: The aims of this study were to report a patient with acute haemolytic transfusion reaction (HTR) after transfusing uncross-matched red blood cell (RBC) units and to identify the frequency of this complication. BACKGROUND: Uncross-matched RBC units are commonly transfused in emergencies, but the frequency of acute HTR is unknown. METHODS: We describe a male stabbing victim who received three units of uncross-matched RBC units complicated by acute intravascular HTR, disseminated intravascular coagulation (DIC) and renal failure. We identified 14 studies evaluating the frequency of acute HTR post-emergency transfusion of uncross-matched RBC units. RESULTS: Acute HTR was shown by haemoglobinuria, free-plasma haemoglobin and methemalbumin, with anti-K and anti-Fya eluted from recipient red cells; acute DIC featured severe hypofibrinogenemia, thrombocytopenia, elevated fibrin D-dimer and multiple bilateral renal infarcts. Two of the three transfused units reacted with pre-existing RBC alloantibodies [anti-K (titre, 128), anti-Fya (titre, 512)], explained by transfusion 25 years earlier. Our literature review found the frequency of acute HTR following emergency transfusion of uncross-matched RBC units to be 2/3998 [0·06% (95% CI, 0·01-0·21%)]. CONCLUSIONS: Although emergency transfusion of uncross-matched blood is commonly practiced at trauma centres worldwide, with low risk of acute HTR (<1/1000), our well-documented patient case demonstrates the potential for acute HTR with severe complications.

A BRIEF OVERVIEW OF COMPARTMENTAL MODELING FOR INTAKE OF PLUTONIUM VIA WOUNDS.

The aim of this study is to present several approaches that have been used to model the behavior of radioactive materials (specifically Pu) in contaminated wounds. We also review some attempts by the health physics community to validate and revise the National Council on Radiation Protection and Measurements (NCRP) 156 biokinetic model for wounds, and present some general recommendations based on the review. Modeling of intake via the wound pathway is complicated because of a large array of wound characteristics (e.g. solubility and chemistry of the material, type and depth of the tissue injury, anatomical location of injury). Moreover, because a majority of the documented wound cases in humans are medically treated (excised or treated with chelation), the data to develop biokinetic models for unperturbed wound exposures are limited. Since the NCRP wound model was largely developed from animal data, it is important to continue to validate and improve the model using human data whenever plausible.

The percutaneous toxicokinetics of VX in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for the decontamination of superficial, nerve agent-contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat™ (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O-ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear. WoundStat™ was applied at 30 seconds post-exposure to assigned animals. The VX contaminant (or saline) and decontaminant remained in place for the duration of the study (up to 6 hours). Physiological parameters and signs of intoxication were recorded during the exposure period. Skin and organ samples were taken post mortem for 14 C-VX distribution analyses. Blood samples were taken periodically for toxicokinetic and whole-blood acetylcholinesterase (AChE) activity analyses. VX exposure was accompanied by a rapid decrease in AChE activity in all animals, regardless of decontamination. However, decontamination significantly improved survival rate and time and reduced the severity of signs of intoxication. In addition, the distribution of 14 C-VX in key internal organs and post mortem blood samples was significantly lower in the WoundStat™ treatment group. This study demonstrates that WoundStat™ may be a suitable medical countermeasure for increasing both survival rate and time following VX exposure. The results also suggest that AChE activity is not a useful prognostic indicator.

[Possibilities of correction rheological blood svoytv at chipped and cut wounds of the breast ].

The purpose: research objective: to study influence of electromagnetic oscillations of millimetric range on rheological properties of blood at patients with chipped and cut wounds of a breast for the purpose of their correction. Methods. For the solution of a research objective we have carried out studying of changes of rheological properties of blood at the 22nd patient with the getting chipped and cut wounds of a breast without internal injury during the next postoperative period. All patient has executed primary surgical processing and drainage of a pleural cavity. At all patients the volume of blood loss has made 200-500 ml. Criteria of inclusion were: existence of the getting wound of a thorax, existence of a small gemotoraks. Criteria of an exception: blood loss existence more than 500 ml, existence of the combined and multiple damages. The main group is divided into two subgroups, in the first 12 patients with application of electromagnetic oscillations of millimetric range, have entered the second 10 people without application of electromagnetic oscillations of millimetric range. The group of comparison was made by 15 rather healthy donor volunteers of the same age and a floor. To all patients the hemotransfusion wasn't carried out, the volume of infusional therapy was comparable in both groups. Changes of a rheology of blood came to light by means of the accounting of viscosity of blood, change of an index of deformation and aggregation of erythrocytes. Conclusion. As a result of the conducted research it is established that application of electromagnetic oscillation of millimetric range for patients with chipped and cut wounds of a breast prevents development of changes of rheological properties of blood, at the same time patients well transfer this procedure that is shown by lack of side effects.

A comparison of base deficit and vital signs in the early assessment of patients with penetrating trauma in a high burden setting.

INTRODUCTION: An assessment of physiological status is a key step in the early assessment of trauma patients with implications for triage, investigation and management. This has traditionally been done using vital signs. Previous work from large European trauma datasets has suggested that base deficit (BD) predicts clinically important outcomes better than vital signs (VS). A BD derived classification of haemorrhagic shock appeared superior to one based on VS derived from ATLS criteria in a population of predominantly blunt trauma patients. The initial aim of this study was to see if this observation would be reproduced in penetrating trauma patients. The power of each individual variable (BD, heart rate (HR), systolic blood pressure (SBP), shock index(SI) (HR/SBP) and Glasgow Coma Score (GCS)) to predict mortality was then also compared. METHODS: A retrospective analysis of adult trauma patients presenting to the Pietermaritzburg Metropolitan Trauma Service was performed. Patients were classified into four "shock" groups using VS or BD and the outcomes compared. Receiver Operator Characteristic (ROC) curves were then generated to compare the predictive power for mortality of each individual variable. RESULTS: 1863 patients were identified. The overall mortality rate was 2.1%. When classified by BD, HR rose and SBP fell as the "shock class" increased but not to the degree suggested by the ATLS classification. The BD classification of haemorrhagic shock appeared to predict mortality better than that based on the ATLS criteria. Mortality increased from 0.2% (Class 1) to 19.7% (Class 4) based on the 4 level BD classification. Mortality increased from 0.3% (Class 1) to 12.6% (Class 4) when classified based by VS. Area under the receiver operator characteristic (AUROC) curve analysis of the individual variables demonstrated that BD predicted mortality significantly better than HR, GCS, SBP and SI. AUROC curve (95% Confidence Interval (CI)) for BD was 0.90 (0.85-0.95) compared to HR 0.67(0.56-0.77), GCS 0.70(0.62-0.79), SBP 0.75(0.65-0.85) and SI 0.77(0.68-0.86). CONCLUSION: BD appears superior to vital signs in the immediate physiological assessment of penetrating trauma patients. The use of BD to assess physiological status may help refine their early triage, investigation and management.

Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.

BACKGROUND: Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. RESULTS: A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. CONCLUSIONS: A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial measurements of plasma SAA could potentially be used as an additional inexpensive, quick and easy tool for monitoring the treatment response in otherwise healthy horses presented with injuries penetrating synovial structures. However further studies will be necessary to ascertain its clinical utility.

Peak creatinine kinase level is a key adjunct in the evaluation of critically ill trauma patients.

BACKGROUND: Elevated creatinine kinase (CK) can indicate rhabdomyolysis, a risk factor for acute kidney injury (AKI). We investigated risk factors and clinical significance of peak CK levels. METHODS: Retrospective analysis, adult trauma patients. Logistic regression was used to identify risk factors for elevated CK and AKI. RESULTS: 3240 trauma patients were analyzed; median time to peak CK was 17 h and 347 patients had peak CK > 5000. On multivariable analysis, younger males with severe injury were more likely to have peak CK > 5000 and peak CK > 5000 was an independent risk factor for AKI (AOR 3.79). Although peak CK levels were significantly lower in older patients (1,637U/L vs 2,604U/L), older patients were more likely to develop AKI at lower CK levels. CONCLUSIONS: CK levels commonly peak within 1-2 days after admission. Despite lower peak CK levels, older patients are more likely to develop AKI. These data may support more rigorous CK monitoring and lower intervention threshold in older patients.

Fatores associados ao óbito e à reposição volêmica em pacientes com trauma por lesões penetrantes / Factors associated with death or volume replacement in patients with trauma due to penetrating injuries

Objective: to evaluate the prognostic factors of volume replacement in patients with trauma due to penetrating injuries. Methods: retrospective cohort study whose data were obtained by analyzing medical records of 544 patients who were admitted to the emergency unit, victims of penetrating trauma. Results: among the victims, 282 (51.9%) suffered stab wound, 262 (48.2%) injury by firearms, 486 (89.3%) were male, 382 (70.2%) were aged between 14 and 30 years. Most who received volume greater than 2000ml, systolic blood pressure ≤90mmHg and mean arterial pressure ≤65mmHg presented more mortality, with p <0.05, p <0.002 and p <0.003, respectively. Conclusion: the limited volume replacement can help in the good prognosis of victims of penetrating trauma.

Avaliar os fatores prognósticos da reposição volêmica em pacientes com trauma por lesões penetrantes. Métodos: estudo de coorte retrospectiva cujos dados foram obtidos através da análise de prontuários de 544 pacientes que deram entrada no serviço de emergência, vítimas de traumatismo penetrante. Resultados: dentre as vítimas, 282 (51,9%) sofreram ferimento por arma branca, 262 (48,2%) ferimento por arma de fogo, 486 (89,3%) eram do sexo masculino, com idade entre 14 e 30 anos 382 (70,2%). A maioria que recebeu fluído maior que 2000ml, pressão arterial sistólica ≤90mmHg e pressão arterial média ≤65mmHg, apresentou mais mortalidade, com valor de p<0,05, p<0,002 e p<0,003, respectivamente. Conclusão: a reposição volêmica limitada pode auxiliar no bom prognóstico do paciente vítima de trauma penetrante.

[PROGNOSTIC SIGNIFICANCE OF CHANGES OF BLOOD GLUCOSE LEVEL IN PATIENTS WITH THORACOABDOMINAL INJURIES.]

Background Currently, one of the causes of high morbidity and mortality is injuries. Predict the outcome of injuries - it is an important task of the treating physician. Trauma is a stress factor so to predict the outcome, you can use markers of stress, the most accessible ofwhich is blood glucose. THE AIM: to reveal the dynamics of the relationship between blood glucose levels and the outlook for the life ofpatients with thoracoabdominal injuries. MATERIALS AND METHODS: A retrospective analysis of medical records of hospitalized patients were divided into two groups, depending on the outlook for the life of (favorable or unfavorable), and each of the groups - into two subgroups according to the presence or absence of signs of intoxication at admission. The subgroups were calculated and compared the mean blood glucose levels at different hours of hospital treatment. RESULTS: It was found that the average blood glucose levels at various hours of hospital stay were significantly higher in patients with poor outcome. The most noticeable was the difference in the first days of hospital treatment. Signs of intoxication was associated with lower values of glucose and a tendency to hypoglycaemia. In addition, among patients with high blood glucose ( 8 mg / dL) was observed over deaths in the first day of hospital stay. CONCLUSION: High blood glucose levels ( 8,0 mmol / L) in the first day of hospital treatment is a predictor ofpoor outcome in patients with thoracoabdominal injuries.