Development of a Sampling and Storage Protocol of Extracellular Vesicles (EVs)-Establishment of the First EV Biobank for Polytraumatized Patients.

In the last few years, several studies have emphasized the existence of injury-specific EV "barcodes" that could have significant importance for the precise diagnosis of different organ injuries in polytrauma patients. To expand the research potential of the NTF (network trauma research) biobank of polytraumatized patients, the NTF research group decided to further establish a biobank for EVs. However, until now, the protocols for the isolation, characterization, and storage of EVs for biobank purposes have not been conceptualized. Plasma and serum samples from healthy volunteers (n = 10) were used. Three EV isolation methods of high relevance for the work with patients' samples (ultracentrifugation, size exclusion chromatography, and immune magnetic bead-based isolation) were compared. EVs were quantified using nanoparticle tracking analysis, EV proteins, and miRNAs. The effects of different isolation solutions; the long storage of samples (up to 3 years); and the sensibility of EVs to serial freezing-thawing cycles and different storage conditions (RT, 4/-20/-80 °C, dry ice) were evaluated. The SEC isolation method was considered the most suitable for EV biobanking. We did not find any difference in the quantity of EVs between serum and plasma-EVs. The importance of particle-free PBS as an isolation solution was confirmed. Plasma that has been frozen for a long time can also be used as a source of EVs. Serial freezing-thawing cycles were found to affect the mean size of EVs but not their amount. The storage of EV samples for 5 days on dry ice significantly reduced the EV protein concentration.

THE INFLUENCE OF CHANGES IN CARBOHYDRATE METABOLISM INDICATORS IN PATIENTS WITH POLYTRAUMA COMPLICATED BY ALCOHOLIC DELIRIUM ON THE CHOICE OF THE SEDATION METHOD.

Topicality: Providing assistance to patients with polytrauma, in a state of alcohol intoxication, complicated by alcoholic delirium, is a serious problem when providing anesthesia care and, in particular, choosing drugs for sedation. Considering the severity of mechanical damage, complications associated with alcohol intoxication and serious biochemical disorders of the body, namely carbohydrate, lipid metabolism, electrolyte changes, on which the activity of all systems depends, it is necessary to study the influence on the course of these processes, depending on the choice of their medicinal corrections. PURPOSE: The purpose of the work is to choose a sedation method to improve the results of treatment of patients with polytrauma and alcohol withdrawal, based on the study of changes in carbohydrate metabolism indicator. MATERIALS AND METHODS: The paper analyzes the results of a study of 80 patients with polytrauma and chronic alcohol intoxication with a state of alcohol withdrawal, complicated by alcoholic delirium, who received intensive therapy in the 12-bed department of anesthesiology and intensive therapy for patients with combined trauma of the KNP «Kharkiv City Clinical Hospital of Emergency Medical Care¼ named after Prof. O. I. Meschaninov¼ KhMR. All patients were diagnosed with polytrauma (thoracic and/or abdominal trauma: rib fractures, hemo-, pneumothorax, hematomas of the liver or spleen, fracture of the bones of the waist, and/or upper and/or lower limbs, fracture of the pelvis). In the course of the research, to achieve the goal, the main indicators of carbohydrate metabolism were determined, which were evaluated by the content of key metabolites: glucose, pyruvic acid, lactate. The study was conducted on the 1st, 3rd and 7th day of hospitalization of the patients. RESULTS AND DISCUSSION: In all traumatized patients with alcohol withdrawal syndrome and alcoholic delirium with the use of dexmedetomidine for sedation (group 1) and in patients who were used as sedatives, diazepam and haloperidol (group 2), changes in these parameters were observed in the blood, compared to healthy people of the control group. As for the glucose content in the blood of the patients of the 1st group, on the first day, persistent hyperglycemia was observed in them 1.7 times higher than this indicator in healthy people. Next, patients' blood glucose levels were determined on the 3rd and 7th day after hospitalization. Glucose content on the 3rd day decreased by 9.4% compared to the level determined on the first day. On the 7th day, the content of glucose in the blood decreased to normal values, which is 26.5% lower compared to the content of glucose in the blood on the first day. In the 2nd group of patients, where diazepam and haloperidol were used on the first day, hyperglycemia was also observed - 1.9 times higher than this indicator in the control group of healthy individuals. On the third day, the level of glucose in the blood decreased by 6%. And on the 7th day, it decreased by 20.5%. Thus, hyperglycemia was observed in the blood of victims with alcohol withdrawal syndrome, complicated by delirium during hospitalization, on the 3rd day of hospitalization (first and second groups) and on the 7th day in patients of the second group, which indicates violation of carbohydrate metabolism and the development of hypoxia, with impaired liver and pancreas function. In accordance with the aim and objectives of the study, the blood content of the main metabolites of glucose metabolism - pyruvate and lactate - was also studied upon admission to the hospital and one week after treatment, which made it possible to comprehensively assess possible carbohydrate metabolism disorders and characterize the features of the body's energy supply in the combination of polytrauma and withdrawal alcohol, complicated by alcoholic delirium. According to the results of the research, there is an increase in the content of lactate and pyruvate in patients with polytrauma against the background of chronic alcoholism compared to healthy people. When analyzing the content of lactate in the blood of patients with polytrauma and alcohol withdrawal syndrome, complicated by alcoholic delirium upon admission to the intensive care unit, a significant increase of this indicator was observed by 97.1% and 113.0%, respectively, in patients of the first and second groups. One week after the intensive therapy, the patients of the 1st group had a significant decrease in the lactate content in the blood - by 13% (Р<0.0001) compared to the content of this indicator at the time of admission to the hospital. In the blood of the patients of the 2nd group, on the 7th day, the lactate content remained unchanged, and by 106.3% it exceeded this biochemical indicator in the blood of the control group. Hyperpyruvatemia was also observed - when entering the hospital in patients of the 2nd group, the content was 55.4% higher compared to healthy people, remained elevated after a week of treatment - by 30.1%, and did not return to normal values. In the patients of the first group, upon admission to the hospital, the pyruvate content in the blood was 53.0% higher compared to the control group, and on the 7th day it significantly decreased by 18.9%, but did not reach the values of the control group (remained at 24, 1% higher compared to the control). The cause of hyperpyruvatemia and hyperlactatemia in patients may also be a violation of their enzymatic transformation into decay products. Lactate is the final product of anaerobic oxidation of glucose, it is formed due to the transformation of pyruvate, under the conditions of action of the lactate dehydrogenase enzyme in conditions of hypoxia. An important indicator of the state of carbohydrate metabolism, namely the balance of anaerobic and aerobic processes in the body, is the lactate / pyruvate ratio, which in the control group was 14.33 [13.82; 14.49]. In the patients of the first group, an increase in this ratio was observed - and it was 18.46 [18.3; 20.59] and 19.81 [18.96; 21,17] upon admission to the intensive care unit and one week after treatment, respectively. Practically the same value of this ratio was observed in patients of the second group - 19.65 [18.97; 22.3] and 22.73 [21.32 23.91], respectively, according to the time of intensive therapy. The latest figures indicate the restructuring of the energy supply of body tissues during the stay of patients in the intensive care unit. CONCLUSIONS: Thus, in patients with polytrauma and alcohol withdrawal syndrome, complicated by alcoholic delirium, there is an intensification of the processes of anaerobic glycolysis, which is evidenced by an increase in the content of pyruvate, lactate, the lactate/pyruvate ratio, and is accompanied by a hypoxic state. When comparing the terms of stay in the intensive care unit, it was determined that the use of dexmedetomidine for the treatment of alcoholic delirium compared to benzodiazepines allows reducing the time of intensive care by 34 hours. Thus, in group 2, the duration of intensive therapy for alcoholic delirium was 89 [82-96.2] hours, while in group 1 it was reduced to 55 [52.2-59.8] (p=0.020427). In addition, it was found that the consumption of drugs by patients was different. During the first day, it was 20 [20-30] mg in group 1, and 40 [40-50] mg in group 2. The groups also differed significantly in terms of the total dose of the drug during intensive therapy, so in patients of group 1, the total consumption was 30 [30-40] mg, in group 2 - 80 [80-90] mg (p=0.033011).

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide.

This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid "repayment of the O2 debt" and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC's) can aggravate the occurrence and severity of complications after trauma. In addition to the "classic" chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC's, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC's. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).

Blood sugar changes and hospital mortality in multiple trauma.

OBJECTIVES: Hyperglycemia with unknown mechanism plays a predictive role in determining the prognosis of multiple trauma patients. The exact time of blood sugar measurement and the role of blood sugar changes in the monitoring of these patients have not been well established. METHODS: This follow-up study was done on multiple trauma patients (>18years) with an Injury Severity Scores (ISS)>16. These patients didn't have any history of diabetes, underlying disease, or drug or alcohol use. Data collection was done by the questionnaire (checklist), and the patients were followed by the medical records. Cox regression was used to measure the effect of independent variables on the patients' hospital mortality. RESULTS: Of a total of 963 patients, 280 patients were enrolled. Of those, 202 were male (72.1%) and 78 were female (27.9%). Hospital mortality was 18 (6.4%). Cox regression analysis suggested that those who had high blood sugar 3h after admission had higher hospital mortality (P=0.04). Changes in blood sugar, ΔBS (BS 3h after admission - BS on admission), in these patients was also significantly correlated with hospital mortality (P<0.001). The multivariate model using the backward conditional method showed that ΔBS (P<0.001), international normalized ration (INR) (P<0.001), and heart rate (P=0.036) were significantly correlated with hospital mortality. CONCLUSIONS: In multiple trauma patients, blood sugar changes in the early hours of admission to the emergency department may help predict hospital mortality, but further studies are needed. Blood sugar monitoring in these patients during this time frame may be helpful in predicting these patients' outcomes. In addition, coagulopathy and tachycardia were significantly associated with hospital mortality.

Polytrauma-induced hepatic stress response and the development of liver insulin resistance.

Insulin resistance and metabolic dysfunction are common following injury. Polytrauma is defined as combined injuries to more than one body part or organ system, and is common in modern warfare, as well as automobile and industrial accidents. Polytrauma can include any combination of burn injury, fracture, hemorrhage, trauma to the extremities, and blunt or penetrating trauma. Multiple minor injuries are often more deleterious than a more severe single injury. To investigate the mechanisms of development of insulin resistance following injury, we have developed a rat model of polytrauma which combined soft tissue trauma with burn injury and penetrating gastrointestinal (GI) trauma. Male Sprague-Dawley rats were subjected to a laparotomy plus either a 15-18% total body surface area scald burn or a single puncture of the cecum (CLP) with a G30 needle, or the combination of both burn and CLP injuries (polytrauma). We examined the effects of polytrauma which increased markers of hepatic endoplasmic reticulum (ER) stress, and increased hepatic Trib3 mRNA levels coincident with reduced insulin-inducible insulin signaling. Phosphorylation/activation of the insulin receptor (IR) and AKT were decreased at 24, but not 6h following polytrauma. These results demonstrate a complex, time-dependent development of hepatic ER-stress and a diminished response to insulin, which were among the pathological sequelae following polytrauma.

Patterns of gene expression among murine models of hemorrhagic shock/trauma and sepsis.

Controversy remains whether the leukocyte genomic response to trauma or sepsis is dependent upon the initiating stimulus. Previous work illustrated poor correlations between historical models of murine trauma and sepsis (i.e., trauma-hemorrhage and lipopolysaccharide injection, respectively). The aim of this study is to examine the early genomic response in improved murine models of sepsis [cecal ligation and puncture (CLP)] and trauma [polytrauma (PT)] with and without pneumonia (PT+Pp). Groups of naïve, CLP, PT, and PT+Pp mice were killed at 2 h, 1 or 3 days. Total leukocytes were isolated for genome-wide expression analysis, and genes that were found to differ from control (false discovery rate adjusted P < 0.001) were assessed for fold-change differences. Spearman correlations were also performed. For all time points combined (CLP, PT, PT+Pp), there were 10,426 total genes that were found to significantly differ from naïve controls. At 2 h, the transcriptomic changes between CLP and PT showed a positive correlation (rs) of 0.446 (P < 0.0001) but were less positive thereafter. Correlations were significantly improved when we limited the analysis to common genes whose expression differed by a 1.5 fold-change. Both pathway and upstream analyses revealed the activation of genes known to be associated with pathogen-associated and damage-associated molecular pattern signaling, and early activation patterns of expression were very similar between polytrauma and sepsis at the earliest time points. This study demonstrates that the early leukocyte genomic response to sepsis and trauma are very similar in mice.

The Use of Circulating miRNAs as Biomarkers for Oxidative Stress in Critically Ill Polytrauma Patients.

BACKGROUND: The diversity of primary and secondary traumatic injuries specific for the critically ill polytrauma patient is complicating the therapeutic management in the absence of a strict assessment of the biological changes. Inflammation, redox imbalance, and immunosuppression can be quantified by various biochemical parameters; however, they do not fully respond to the current requirements. Another phenomenon responsible for worsening the clinical status and for the development of complications in such patients is oxidative stress. Its aggressiveness combined with biochemical and physiological imbalances leads to increased morbidity and mortality. To minimize the effects induced by free radicals, various substances are administered with high antioxidant capacity. However, the dosage optimization for each patient is difficult without strict monitoring of oxidative stress. In this paper we will summarize and present the pathophysiology of oxidative stress, as well as the specificity of miRNAs for a series of molecular changes at the cellular level. METHODS: For this study the available literature on specific databases such as PubMed, Embase and Scopus was thoroughly analyzed. Each article has been carefully reviewed, extracting useful information for this study. The keywords used to select the relevant articles were "oxidative stress", "antioxidant therapy", "microRNAs biomarkers", and "critically ill patients". RESULTS: For this study, 121 scientific articles relevant to our topic were analyzed. Currently, quantification of oxidative stress is achieved through indirect correlations with plasma levels of specific biomarkers. For a more specific evaluation of the redox status, numerous studies were conducted on the use of circulating miRNAs as biomarkers in this regard. CONCLUSIONS: Introducing miRNAs can revolutionize both monitoring and therapy modulation in these patients, adapting to the organic damage.

Using Circulating miRNAs as Biomarkers for the Evaluation and Monitoring of the Mitochondrial Damage in the Critically Ill Polytrauma Patients.

BACKGROUND: The multiple-traumatic critical patient presents a variety of pathophysiological, cellular, and molecular dysfunctions. One of the most important is represented by mitochondrial damage which afterwards is responsible for the augmentation and worsening of a series of pathologies that lead to the worsening of the clinical status of the patient. The severe inflammatory response, sepsis, and the redox imbalance are other pathologies that together with the multiple traumas are responsible for the mitochondrial dysfunctions. As an overview, we can say that both the mitochondrial damage as well as the clinical statuses of those patients are responsible for an increase in the chances of multiple organ dysfunction syndrome and death of critical patients with multiple trauma from the Intensive Care Units (ICU). In this paper we wish to summarize the microRNAs that can be used as biomarkers for evaluation and monitoring of the mitochondrial activity in critical patients with multiple traumas. METHODS: For the paper, literature available in the international databases PubMed and Scopus until the year 2015 has been consulted. The key words used for the article search were "mitochondrial damage", "microRNAs biomarkers", and "critically ill polytrauma patients". RESULTS: As a result of the research based on the key words presented above, we found 234 papers. From those, after rigorous analysis 64 were selected as being in conformity with the needs of this paper. CONCLUSIONS: The critical polytrauma patient needs a specific evaluation and monitoring due to the complexity of the dysfunctions that appear at the cellular level. The use of microRNAs as biomarkers for the mitochondrial damage can be of real use for intensive care medicine. Nevertheless, more studies are required in order to determine a larger panel of microRNAs which can have an impact on mitochondrial damage.

Using the Expression of Damage-Associated Molecular Pattern (DAMP) for the Evaluation and Monitoring of the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient continues to be one of the most complex cases in the intensive care unit (ICU). The molecular damage is closely connected with the severe, specific pathophysiological imbalances, such as severe inflammation, infections, hypermetabolism, oxidative stress, and ultimately multiple organ dysfunction syndrome (MODS). METHODS: The literature available on PubMed and Scopus was analysed for this study. The key words used in the search were "biomarkers in critically ill patients", "molecular damage", "sepsis biomarkers", "miRNAs biomarkers", and "oxidative stress". RESULTS: After reviewing the available literature, 133 science articles were selected. According to recent studies, the gold goal in the management of the critically ill patient is the optimization of intensive care therapy dependent on the molecular damage. CONCLUSIONS: Furthermore, evaluation, monitoring, and therapy adaptation in this type of patient is closely related to the biochemical and molecular disorders.

The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient, apart from the primary, traumatic injuries and the secondary, port-traumatic injuries, presents with a series of molecular disasters. Dysfunctions of the biochemical pathways and molecular damage add to the worsening of the clinical status of these patients, one of the most well-known molecular phenomena being oxidative stress (OS), responsible for an escalation of the inflammatory status, multiple infections, and multiple organ dysfunction syndrome (MODS). METHODS: For this study was analysed the literature available on PubMed and Scopus. The key words used in the search were "oxidative stress", "lipid peroxidation", "critically ill", "polytrauma patients", and "biomarkers oxidative stress". RESULTS: For the study we selected 47 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals (FR), which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: One of the most aggressive redox mechanisms related to lipid molecules is known as lipid peroxidation (LPOX).

Advances in Biomarkers in Critical Ill Polytrauma Patients.

BACKGROUND: The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient. In this paper we wish to summarize the recent studies of biomarkers useful for the intensive care unit (ICU) physician. METHODS: For this study the available literature on specific databases such as PubMed and Scopus was thoroughly analyzed. Each article was carefully reviewed and useful information for this study extracted. The keywords used to select the relevant articles were "sepsis biomarker", "traumatic brain injury biomarker" "spinal cord injury biomarker", "inflammation biomarker", "microRNAs biomarker", "trauma biomarker", and "critically ill patients". RESULTS: For this study to be carried out 556 original type articles were analyzed, as well as case reports and reviews. For this review, 89 articles with relevant topics for the present paper were selected. The critically ill polytrauma patient, because of the clinical complexity the case presents with, needs a series of evaluations and specific monitoring. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients. CONCLUSIONS: The biomarkers existing today, with regard to the critically ill polytrauma patient, can bring a significant contribution to increasing the survival rate, by adapting the therapy according to their expressions. Nevertheless, the necessity remains to research new non-invasive diagnostic methods that present with higher specificity and selectivity.

Modulation of the Redox Expression and Inflammation Response in the Critically Ill Polytrauma Patient with Thoracic Injury. Statistical Correlations between Antioxidant Therapy.

BACKGROUND: One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables. METHODS: This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death. RESULTS: Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865). CONCLUSIONS: Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

The Expression of Nuclear Transcription Factor Kappa B (NF-κB) in the Case of Critically Ill Polytrauma Patients with Sepsis and Its Interactions with microRNAs.

Critical polytrauma patients present a series of pathophysiological disturbances, biochemical and molecular dysfunction, which comprise to be the major cause of intensive care unit admission. In regard to molecular damage, there exists a series of factors, which all together contribute to the aggravation of the clinical status leading to increased mortality rate in these patients. One of the most important biochemical factors involved is the nuclear transcription factor B (NF-κB). Impaired NF-κB functioning is reflected on the clinical status of the patient through increased production of pro-inflammatory molecule, leading to multiple organ dysfunction syndrome. In addition to this, through microRNAs interactions, various pathophysiological as well as biochemical disturbances are produced, which altogether further reduce the patient's survival rate. In this paper, we would like to present the modifications seen in the expression of NF-κB in critically polytraumatized patients with sepsis. In additions to this, we would like to discuss the correlation between the microRNAs and its further implications in clinical status of these patients.

[METABOLIC PREVENTION OF FAT EMBOLISM.]

THE AIM: to study the effect of solution with methionine "Remaxol" on metabolic disorders andfat embolism developing in severe combined trauma. MATERIALS AND METHODS: 544 patient with severe skeletal trauma were undergone to a prospective study of dynamics of fat embolism syndrome development depending on the inclusion in the program of infusion therapy drug "Remaxol". The dynamics of lactate, glucose, free fatty acids, globularia and the incidence offat embolism syndrome were analyzed. RESULTS: Corrective action drug with methionine "Remaxol" on hyperglycemia, hyperlactatemia, hyperlipemia and de- crease circulation offat globules, which is reflected in the decrease in the frequency of development offat embolism syndrome was identified. CONCLUSION: One of the proposed mechanisms reduce the risk offat embolism development is assumed restoration of endogenous carnitine synthesis with methionine and transport offree fatty acids in the cell and their subsequent inclusion in metabolic processes.

Dynamic neuroendocrine changes in critically ill patients with polytrauma.

OBJECTIVE: Acute multiple-trauma induces activation of neuroendocrine system. Nonthyroidal illness syndrome (NTIS) is considered to be associated with adverse outcome in intensive care unit (ICU) patients. This study was aimed to assess dynamic changes of neuroendocrine hormones in patients with polytrauma and their association with the polytrauma score (PTS). METHODS: Blood samples from 24 critically ill patients with polytrauma were obtained on 1st, 2nd, 3rd and 7th day after admission to ICU for analysis of thyroid-stimulating hormone (TSH), total triiodothyronine (T3); free triiodothyronine (fT3), total thyroxine (T4), free thyroxine (fT4), growth hormone (GH), prolactin (PRL) and procalcitonin levels. RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16±5 points on average at the admission to ICU. All patients had normal baseline TSH, T4, fT4, but low T3, and fT3 levels were found in 20% and 33% ICU patients, respectively. On the 7th day after admission to ICU TSH had tendency to increase (p=0.07) and fT4 significantly decreased (p=0.03). The PRL level significantly increased on the 3rd day after admission as compared to 1st day (p=0.04). PTS positively correlated with fT3 (r=0.582, p=0.004) and negatively with fT4 (r=-0.422, p=0.04) at the 1st day in ICU. CONCLUSION: Critical illness in patients with polytrauma leaded to trauma severity-dependent alterations of the thyroid axis response early after injury. Our findings suggest that detection of dynamic hormonal response is more appropriate than single measurement. However supplemental therapy for NTIS should be used after more detailed studies are completed.

Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed.

BACKGROUND: Treatment with oral carbohydrate prior to trauma and hemorrhage confers a survival benefit in small animal models. The impact of fed states on survival in traumatically injured humans is unknown. This work uses regulatory networks to examine the effect of carbohydrate pre-feeding on metabolic response to polytrauma and hemorrhagic shock in a clinically-relevant large animal model. METHODS: Male Yorkshire pigs were fasted overnight (n = 64). Pre-fed animals (n = 32) received an oral bolus of Karo\textregistered\syrup before sedation. All animals underwent a standardized trauma, hemorrhage, and resuscitation protocol. Serum samples were obtained at set timepoints. Proton NMR was used to identify and quantify serum metabolites. Metabolic regulatory networks were constructed from metabolite concentrations and rates of change in those concentrations to identify controlled nodes and controlling nodes of the network. RESULTS: Oral carbohydrate pre-treatment was not associated with survival benefit. Six metabolites were identified as controlled nodes in both groups: adenosine, cytidine, glycerol, hypoxanthine, lactate, and uridine. Distinct groups of controlling nodes were associated with controlled nodes; however, the composition of these groups depended on feeding status. CONCLUSIONS: A common metabolic output, typically associated with injury and hypoxia, results from trauma and hemorrhagic shock. However, this output is directed by different metabolic inputs depending upon the feeding status of the subject. Nodes of the network that are related to mortality can potentially be manipulated for therapeutic effect; however, these nodes differ depending upon feeding status.

[CLINICAL EFFECTS OF IMMUNONUTRITION IN THE TREATMENT OF POLYTRAUMA PATIENTS].

Trauma is an important issue, as they make significant contributionin structure of disability and mortality. Pathological processes developing in traumatic disease are diverse and require a differentiated approach of the treatment. The review contains the main information about the nutrients used in the relief of the hypermetabolism-hypercatabolism syndrome, and highlighted the role of pharmaconutrition in treatment of that group of patients.

[POSSIBILITY OF CORRECTION OF METABOLIC DISORDERS WITH REAMBERIN IN ACUTE PERIOD OF TRAUMATIC INJURY].

56 patients at the age of 18-60 years with severe trauma were examined. Influence of the polyelectrolytic (Reamberin)solution on an acid-base state, osmolarity and electrolytic composition of plasma in the acute posttraumatic period was evaluated. It was found that patients, who was treated by isotonic sodium chloride solution and Ringer's solution, had metabolic acidosis and hyperchloremia. In contrast, in the reamberin group 82% of patients had lower concentrations of chloride and had nothing acid-base disturbances on the second day after trauma. Reamberin didn't influence on plasma osmolarity and the rate of metabolic alkalosis during the acute period of a trauma.

The antimicrobial peptide lysozyme is induced after multiple trauma.

The antimicrobial peptide lysozyme is an important factor of innate immunity and exerts high potential of antibacterial activity. In the present study we evaluated the lysozyme expression in serum of multiple injured patients and subsequently analyzed their possible sources and signaling pathways. Expression of lysozyme was examined in blood samples of multiple trauma patients from the day of trauma until 14 days after trauma by ELISA. To investigate major sources of lysozyme, its expression and regulation in serum samples, different blood cells, and tissue samples were analysed by ELISA and real-time PCR. Neutrophils and hepatocytes were stimulated with cytokines and supernatant of Staphylococcus aureus. The present study demonstrates the induction and release of lysozyme in serum of multiple injured patients. The highest lysozyme expression of all tested cells and tissues was detected in neutrophils. Stimulation with trauma-related factors such as interleukin-6 and S. aureus induced lysozyme expression. Liver tissue samples of patients without trauma show little lysozyme expression compared to neutrophils. After stimulation with bacterial fragments, lysozyme expression of hepatocytes is upregulated significantly. Toll-like receptor 2, a classic receptor of Gram-positive bacterial protein, was detected as a possible target for lysozyme induction.

Traumatic brain injury and its effect on coagulopathy.

Polytraumatic injury results in tissue factor (TF) release from damaged cells. The acute coagulopathy of trauma (ACT) occurs early and results from significant tissue injury and tissue hypoperfusion. ACT is augmented by therapies resulting in acidemia, hypothermia, and hemodilution contributing to trauma-induced coagulopathy. Coagulopathy associated with traumatic brain injury (TBI) results from the interplay of numerous variables. Because of the high concentration of TF in brain tissue, TBI has been believed to be associated with a greater degree of coagulopathy compared with injury in other body systems. TBI has also recently been shown to cause platelet dysfunction. Platelet receptor inhibition prevents cellular initiation and amplification of the clotting cascade, limiting thrombin incorporation, and stabilization of clot to stop hemorrhage. Therefore, head injury in the presence of polytrauma does appear to augment ACT and warrants close monitoring and appropriate intervention.