Multiorgan Metabolomics and Lipidomics Provide New Insights Into Fat Infiltration in the Liver, Muscle Wasting, and Liver-Muscle Crosstalk Following Burn Injury.

Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victims, due to liver failure and muscle wasting. Metabolic changes may persist up to 2 years following the injury. Thus, understanding the underlying mechanisms of the pathology is crucially important to develop appropriate therapeutic approaches. We present detailed metabolomic and lipidomic analyses of the liver and muscle tissues in a rat model with a 30% body surface area burn injury located at the dorsal skin. Three hundred and thirty-eight of 1587 detected metabolites and lipids in the liver and 119 of 1504 in the muscle tissue exhibited statistically significant alterations. We observed excessive accumulation of triacylglycerols, decreased levels of S-adenosylmethionine, increased levels of glutamine and xenobiotics in the liver tissue. Additionally, the levels of gluconeogenesis, glycolysis, and tricarboxylic acid cycle metabolites are generally decreased in the liver. On the other hand, burn injury muscle tissue exhibits increased levels of acyl-carnitines, alpha-hydroxyisovalerate, ophthalmate, alpha-hydroxybutyrate, and decreased levels of reduced glutathione. The results of this preliminary study provide compelling observations that liver and muscle tissues undergo distinctly different changes during hypermetabolism, possibly reflecting liver-muscle crosstalk. The liver and muscle tissues might be exacerbating each other's metabolic pathologies, via excessive utilization of certain metabolites produced by each other.

Experience of outreach in a resource-constrained environment: 10 years of outcomes in burn care.

OBJECTIVE: The objective of this work was to describe an efficient and sustainable outreach model in a resource-constrained environment, with a multifaceted approach focusing on national policy change, telemedicine, injury prevention, education and treatment of burns. SUMMARY BACKGROUND DATA: Burn injury constitutes a significant portion of morbidity and mortality worldwide, particularly in children, and in low- and middle-income countries. METHODS: We reviewed the impact of ten-years of a burn outreach program. Our focus was on clinical data on burn care within one region of Ukraine. We assessed knowledge of burn prevention/first aid utilizing a large survey, analyzed clinical data from our outreach clinic and telemedicine program, and analyzed data within a newly created burn repository within Ukraine. RESULTS: A national burn prevention policy has been implemented through our efforts along with a burn prevention program. Educational efforts have led to improvements of major complication rates (wound infection [7% vs. 16%], pneumonia [2.4% vs. 0.3%], sepsis [1.6% vs. 0.6%], UTI [2% vs. 0.6%], and cellulitis [11% vs. 3.4%]), respiratory support of acutely ill patients [1.3% vs. 0.4%], and blood transfusion triggers. CONCLUSIONS: Broadly, our model could be an example of building sustainable outreach programs in resource-constrained environments. Through collaboration with local healthcare providers, we have developed and implemented an outreach program in a resource-constrained environment.

The selenium status of pediatric patients with burn injuries.

BACKGROUND: Dietary selenium (Se) requirements during critical illness are not well known. The objective of this study was to assess the longitudinal Se status of pediatric patients with burns. METHODS: Twenty patients admitted to our hospital with burns exceeding 10% of their total body surface area were studied longitudinally during the first 8 weeks of admission or until 95% wound closure was achieved. Dietary Se intake was calculated daily, and plasma and urine samples were collected weekly for analyses of plasma Se, urinary Se, and glutathione peroxidase activity. RESULTS: Patients included in this study were individuals with an average age of 6.5 years ± 5.3 years and with burn injury of a mean total body surface area of 42% ± 21%. Dietary Se intake throughout the study (mean = 60 µg/d ± 39 µg/d) was consistent with established standards for healthy children and did not change throughout the study. Plasma Se (mean = 1.08 µmol/L ± 0.34 µmol/L) and plasma glutathione peroxidase (mean = 3.2 U/g protein ± 1.42 U/g protein) were below reported normal values for healthy American children. Mean urinary Se excretion (65.9 µg/L ± 50 µg/L) exceed dietary Se intake. Plasma Se was inversely related to incidence of total infection (p = 0.04). CONCLUSIONS: Results from this study indicate that Se status is depressed among pediatric patients with burns and that recommended Se intake for healthy children is likely insufficient for this population. Further studies are necessary to elucidate the amount of dietary Se required to maximize Se stores among pediatric patients with burn injuries.

Specific Patterns of Postoperative Temperature Elevations Predict Blood Infection in Pediatric Burn Patients.

Using readily available temperature data, we seek to propose a scoring criteria that can facilitate accurate and immediate prediction of blood infection. The standard in diagnosing blood infection is a positive blood culture result that may take up to 3 days to process, requiring providers to make a prediction about which febrile patient is actually bacteremic. This prediction is difficult in burned children as systemic inflammation can cause fever in the absence of infection. An ability to make this prediction more accurate using readily available information would be useful. A retrospective chart review was performed for 28 pediatric patients, with a burn size 20% or greater, admitted to the burn unit between 2010 and 2014. All children had blood cultures drawn. They were divided into either infection (positive blood cultures) or control (negative blood cultures) groups. Median temperature and mean number of temperature elevations were compared between the two groups. We evaluated the predictive accuracy of using temperature elevation, pattern, and timing to predict blood infection. A significant difference was seen in the mean number of temperature elevations above 39°C. This was significant for each time stage, especially in the 0- to 24-hour post-surgery period. We found the most predictive accuracy in the 0- to 12-, 12- to 38-, and 12- to 48-hour time periods. We found a strong association between mean number of fever spikes above 39°C and blood infection, especially 12 to 24 hours after surgery. This readily available data can be useful to clinicians as they access children with burns.

Practical guidelines for nutritional management of burn injury and recovery.

Nutrition practice in burn injury requires a multifaceted approach aimed at providing metabolic support during a heightened inflammatory state, while accommodating surgical and medical needs of the patient. Nutritional assessment and determination of nutrient requirements is challenging, particularly given the metabolic disarray that frequently accompanies inflammation. Nutritional therapy requires careful decision making, regarding the safe use of enteral or parenteral nutrition and the aggressiveness of nutrient delivery given the severity of the patient's illness and response to treatment. With the discovery that specific nutrients can actually alter the course of disease, the role of nutrition support in critical illness has shifted from one of preventing malnutrition to one of disease modulation. Today the use of glutamine, arginine, essential fatty acids, and other nutritional factors for their effects on immunity and cell regulation is becoming more common, although the evidence is often lagging. An exciting dichotomy exits, forcing nutrition support specialists to make responsible choices while remaining open to new potential helpful therapeutic options.

Measures of Total Energy Expenditure and Its Components Using the Doubly Labeled Water Method in Rehabilitating Burn Children.

BACKGROUND: A persistent hypermetabolic state delays anabolism and growth in burned children. However, our own clinical experience has been that resting energy expenditure (REE) is not increased during the rehabilitative phase, suggesting other contributing factors. We measured total energy expenditure (TEE) and its components in rehabilitating pediatric burn patients to identify the basis for accelerated energy metabolism in this population. MATERIALS AND METHODS: Children admitted with initial burns of 20% of their total body surface area (TBSA) or greater were enrolled into this prospective, descriptive study. TEE was measured using the doubly labeled water method over a 7-day period. During that period, REE was measured on 2 days by indirect calorimetry. Activity energy expenditure (AEE) was assessed using a physical activity monitoring device for a 24-hour period. TEE and REE were compared with sex-specific, age-matched, and weight-matched norms using the Dietary Reference Intakes (DRI) standards. RESULTS: Ten children with an average burn size of 53.7% ± 20% (range, 27%-82%) of TBSA completed this study. Their mean age and weight were 10.4 ± 5.5 years and 35.8 ± 16.4 kg, respectively. Daily TEE averaged 66 kcal/kg and was 1.08% of reference DRI. REE was 92% ± 25% of predicted basal metabolic rate, not exceeding 120% as a maximum value in any child. CONCLUSIONS: TEE and REE in rehabilitating burn children are comparable to reference standards. Increased REE was not typical in our population, but measures of AEE were commonly high.

Post-operative pain control for burn reconstructive surgery in a resource-restricted country with subcutaneous infusion of local anesthetics through a soaker catheter to the surgical site: Preliminary results.

OBJECTIVE: Post-operative pain can significantly affect a patient's ability to recover following surgery. In this study we introduced the concept of post-operative pain evaluation of burn patients as well as a technique for placement and use of subcutaneous catheters for continuous infusion of local anesthetic to provide analgesia following skin harvest from the lateral thigh in a hospital in resource-restricted country--Ukraine. METHODS: A total of 109 patients were enrolled in this study. In the control group 64 patients received the standard post-operative pain regimen of metamizole 1 g and/or ketorolac 3%- 30 mg at the discretion of the nursing staff. In the interventional group, 45 patients received the catheter infusion of local anesthetic by elastomeric pump which was placed intraoperatively; it continuously delivers a regulated flow 4-5 ml/h of procaine 0.5% for 48 h to a patient's surgical donor site with the standard pain regimen available for breakthrough pain. All patients were assessed post-operatively and in the peri-dressing change period by the nursing staff. Blood pressure, heart rate, and pain scores were documented based on the Wong-Baker Faces Pain Rating Scale. All data were analyzed using SAS version 9.3. The Student's t test and Fisher's exact test were used to assess differences between groups for continuous variables. The Mann-Whitney U Test was used to examine differences in pain scores between groups. A p value of <0.05 was considered significant. RESULTS: The median pain score immediately following surgery was 5.0 in the control group, which was significantly greater (p=0.03) than median pain score of 4.0 for the patients receiving continuous infusion of procaine. However, there is no statistically significant difference in the median pain score (3.0 and 3.0) after the initial dressing change (p=0.73). CONCLUSIONS: Our Ukrainian colleagues now have a method of objective pain assessment and a new technique in pain management. With assessment linked to intervention, improvement in post-operative pain can be expected.

Case of extreme growth deceleration after burns.

Studies have demonstrated deceleration in both weight and height following burns in children. It is expected patients will display catch up growth and return to normal weight within three years but continued height deficiency may remain in cases of severe burns. We describe a case of severe growth retardation of 8 years old orphan child from Ukraine who suffered of burn less than 40% of total body surface area when he was a 3 years of life. His case was complicated by domestic abuse, neglect and limited medical care. He initially presented to the United States for surgical care of his contractures but his treatment quickly focused on his profound growth retardation. Despite aggressive nutritional supplementation and evaluation he did not demonstrate any weight gain.

Improving burn care and preventing burns by establishing a burn database in Ukraine.

BACKGROUND: Burns are a challenge for trauma care and a contribution to the surgical burden. The former Soviet republic of Ukraine has a foundation for burn care; however data concerning burns in Ukraine has historically been scant. The objective of this paper was to compare a new burn database to identify problems and implement improvements in burn care and prevention in this country. METHODS: Retrospective analyses of demographic and clinical data of burn patients including Tukey's post hoc test, analysis of variance, and chi square analyses, and Fisher's exact test were used. Data were compared to the American Burn Association (ABA) burn repository. RESULTS: This study included 1752 thermally injured patients treated in 20 hospitals including Specialized Burn Unit in Municipal Hospital #8 Lviv, Lviv province in Ukraine. Scald burns were the primary etiology of burns injuries (70%) and burns were more common among children less than five years of age (34%). Length of stay, mechanical ventilation use, infection rates, and morbidity increased with greater burn size. Mortality was significantly related to burn size, inhalation injury, age, and length of stay. Wound infections were associated with burn size and older age. Compared to ABA data, Ukrainian patients had double the length of stay and a higher rate of wound infections (16% vs. 2.4%). CONCLUSION: We created one of the first burn databases from a region of the former Soviet Union in an effort to bring attention to burn injury and improve burn care.

Asymptomatic hyperamylasemia and hyperlipasemia in pediatric patients with toxic epidermal necrolysis.

Although pancreatitis is rare in pediatric burn patients, elevated pancreatic enzymes have been recently observed among toxic epidermal necrolysis (TEN) patients. This clinical phenomenon has implications particularly for the nutritional management of patients involved. The objective of this study was to assess the frequency of sustained, elevated amylase, and lipase enzymes among children with TEN or Stevens Johnson Syndrome (SJS) and to evaluate the utilization of enteral nutrition support in this population. Medical records of 24 patients admitted to our hospital between January 1994 and October 2008 with TEN or SJS were retrospectively reviewed. Only patients with > or =4 consecutive measures for both amylase and lipase were included in this study (n = 10). Serial laboratory values were collected during the first 30 days of disease. Four patients (40%) had elevated amylase and lipase values, whereas six patients had values within normal limits. Patients with elevated pancreatic enzymes were significantly younger in age (4.7 +/- 1.7 years) than patients without elevated enzymes (11 +/- 5.9 years) and also had a higher incidence of sepsis. All other characteristics were similar between the groups. Enteral nutrition support was initiated within 4 days of admission in all 10 patients and did not correlate with elevated enzymes. Our findings suggest that hyperlipasemia and hyperamylasemia can occur in the pediatric population with TEN or SJS. Although the sample size in this study makes it difficult to determine the cause, sepsis may have been a contributing factor. In the absence of symptomatic pancreatitis, patients with TEN can safely meet nutritional goals orally or with standard enteral nutrition support.

The contribution of muscle to whole-body protein turnover throughout the course of burn injury in children.

The physiologic response to trauma results in the efflux of large amounts of amino acids from skeletal muscle. This is extreme in large burn injuries. Protein kinetic studies, although useful in determining the rates of protein synthesis and breakdown, do not provide information about muscle loss. This study determined the contribution of muscle protein to whole-body protein breakdown in children throughout their course of burn injury. Children aged 0 to 18 years with initial burn size ≥30% TBSA underwent ¹5N glycine and 3 methylhistidine (3MH) analysis during three phases of care: A, early acute; B, wound closure; and C, convalescence. Muscle protein breakdown was estimated using a factor of 4.2 µmol 3MH per 1 g of mixed protein. Twenty-two patients with a mean of 54.5 ± 20.1% TBSA burn were studied. Protein balance did not change remarkably and remained positive by 2 g/kg during hospitalization. However, muscle protein breakdown dropped from 1.1 to 0.6 g/kg with wound closure (P < .0001), representing a decrease in the contribution of muscle protein to whole-body protein breakdown from 20 to 7%. Ten patients returned for a third measurement after discharge. Although protein turnover was high, muscle breakdown was consistent with 3MH values reported in healthy children. Serial determination of 3MH excretion is a simple way to track muscle catabolism throughout burn injury. Our data suggest that despite accelerated protein turnover, muscle catabolism significantly decreases with wound closure and begins to normalize around discharge. In convalescence, 3MH excretion is comparable with normal children.

Malnutrition among pediatric burn patients: A consequence of delayed admissions.

Early definitive burn treatment is assumed to improve prognosis, in part because open wounds rapidly stimulate muscle catabolism and systemic inflammation. This study describes the incidence and management of injury associated malnutrition among pediatric burn patients transferred for definitive care 21-166 days following burn injury. Medical records of patients admitted to our hospital between January 2003 and January 2009, at least 3 weeks after burn injury, were retrospectively reviewed. Only children with an initial total body surface area (TBSA) burn of ≥20% were included in this study (n=36). Patients were classified as acutely well nourished or malnourished by the medical team. All patients were admitted with chronic open wounds (31±16% TBSA). Sixty-one percent (n=22) of patients were diagnosed with malnutrition. These patients had a significantly longer delay to transfer (26-166 days) than well nourished patients who transferred at 21-138 days (p<0.05). Average protein (2.8±0.18g/kg), and kilocalorie (1.6±0.1% basal metabolic rate) provision did not differ between groups. Incidence of infection was not different between well nourished and malnourished patients. Malnutrition occurs frequently among pediatric burn patients with delayed admissions. Adequate surgical care, infection control, and nutrition are required for wound healing.

Maternal selenium nutrition and neonatal immune system development.

We evaluated the impact of dietary selenium intake on neonatal immune cell differentiation and function. A low selenium intake during pregnancy and lactation produced reductions in maternal plasma selenium (33%, p = 0.0001), milk selenium (36%, p = 0.001), and corresponding neonatal plasma selenium (47%, p = 0.008). Thymocytes from neonates receiving low-selenium milk showed an impaired activation in vitro (p = 0.001). The percentages of CD8 cytotoxic T cells (p = 0.03), CD2 T cells (p = 0.09), panB cells ( = 0.02), and natural killer cells (p = 0.07) were all decreased in neonates nursed by mothers fed a low-selenium diet. The results indicate that maternal selenium intake impacts neonatal selenium status which in turn influences the neonatal immune system development.