Body Surface Area Full Thickness Research Articles

109 Effects of Fat-Rich Nutrients in the Pancreas of an Experimental Burn Model

Abstract Introduction Oversupply of nutrients overstimulates beta cells in standard conditions, and severe burn injuries increase the metabolic needs. In this study, we investigated the effects of fat-rich nutrients on the endocrine pancreas during the acute phase of severe burns. Methods Twenty-one Wistar albino rats were randomly divided into 3 groups. Two groups were fed with standard commercial rat chow (1 with sham procedure and 1 with burn procedure), and the third group (also with burn procedure) was fed a fat-rich diet (60% kcal fat). The burn procedure involved a 25% total body surface area fullthickness burn. Blood samples were taken at 36 hours and 7 days after burn injury or sham procedure. On postburn day 7, skin biopsies were taken and a pancreatectomy was performed. Pancreatic tissues were examined under light microscopy; islets size and cellularity were calculated and investigated immunohistochemically. Results Plasma glucose, C-Peptide, and insulin levels were similar in all the study groups 36 hours and 7 days after burn induction or sham procedure. There was a significant increase in the number of cells per one islet in the burn group given a fat-rich diet compared with the other groups (P = .05). Caspase-3 was strongly expressed in both groups with burn injuries. Conclusions Overconsumption of certain fats can lead to a compensatory response by beta cells that eventually can progress to beta-cell dysfunction during the acute phase of burns. Severe burns induce pancreatic islet cell hyperplasia. Providing excessive fat nutrients during the acute postburn period attenuates this response. Despite the morphophysiological changes observed in the pancreas, all animals in our study achieved similar glycemic homeostasis. Applicability of Research to Practice The delivery of nutritional support is a vital element of burn care, and the main goal is simply to avoid nutritional complications. Lipotoxicity contributes to multisystem organ failure and worse clinical outcomes in obese patients and mice with pancreatitis. Neutralization of IL-1β produces beneficial effects on postburn glycemic control and improves survival. apoptosis in the pancreas of patients with severe burns may be linked to a series of events that can induce Caspase-1 activation and IL-1β release, and these pathways may be influenced by the nutritional status, especially in the early postburn phase. Effective nutritional assessment and management can optimize wound healing and decrease complications and mortality.

549 Lessons Learned from Two Survivors of Greater Than 90% Total Body Surface Area Full Thickness Burn Injuries Using a Dermal Biodegradable Substitute and Autologous Skin Cell Suspension: A Case Series

Abstract Introduction Advances in burn injury knowledge, critical care, and pharmacological developments have increased survival rates among extensive burn patients. Survival now dependents not just on skin coverage, but effective control of SIRS response, metabolic derangement, fluid loss and sepsis. Novel synthetic dermal substitutes create robustness, thickness, and pliability of the skin in addition to an improved aesthetic appearance while; point-of-care autologous skin cell harvesting enhances treatment by amplifying small split-thickness skin samples to produce an autologous skin cell suspension (ASCS) to cover a larger burn area. This study reports on two survivors with greater than 90% total body surface area full-thickness burns utilizing a combined treatment of a dermal substitute along with ASCS and traditional burn management strategies. Methods Chart review of two patients with >90% burns and inhalation injury after being trapped in a burning vehicle following a traffic collision occurred. Most of the burns in both patients were “leathery” and consistent with full thickness, sparing only the plantar and dorsal aspect of the feet and bilateral small areas of the hip in Patient 1. Patient 2 had fourth-degree burns in some areas of the chest and flank with only the bilateral groin regions and feet spared. The patients were treated with a multi-step process which included using allograft, dermal substitute, and ASCS with split-thickness skin grafts (STSG) in place of cultured epidermal autograft to achieve coverage of >90% burns with high meshed ratio. Results The dermal substitute was limited to deep burns that penetrated down to fat, muscle, and/or joints. Fluid loss was well controlled by the dermal substitute during initial resuscitation. Post reconstruction, areas covered with the dermal substitute and grafted with autogenous STSG with ASCS exhibited less hypertrophy and contracture bands. The elbow and knee joints showed minimal restriction with passive motion and good skin compliance, but contractures persisted in areas where 4th degree tendon and fascia thermal injury occurred. Areas that showed signs of infection were trimmed or unroofed and allowed to drain while maintaining the remainder of the dermal substitute. Conclusions The use of dermal substitutes and ASCS allowed the care team to achieve SIRS control, improved fluid management, enhanced skin coverage, and reduced hospitalization stay. The process experienced in these cases shows promise for future patients with extensive burns. Both patients were able to survive and show improvement during rehabilitation.

Clinical characteristics and risk factors for severe burns complicated by early acute kidney injury.

Early acute kidney injury (AKI) is a frequent fatal complication of severely burned patients. Although significant progress has been made in fluid resuscitation, intensive care, and renal replacement therapy (RRT) technology in recent years, the incidence and mortality rate in severely burned patients with AKI remains considerable. This study aims to provide theoretical evidence for prevention and treatment by investigating the clinical characteristics and risk factors influencing the incidence and severity of early AKI in severely burned patients. This 3-year retrospective, single-center study was conducted in critically ill burned patients admitted to the Burn ICU at Guangzhou Red Cross Hospital of Jinan University. Patients whose age is older than 18 years with ≥30% burned total body surface area (TBSA) were enrolled in this study. Those patients who arrived at our burn ICU>72h after injury or died within 48h from arrival were excluded. Data of 128 patients were studied in the final. Demographic and injury details were recorded. KDIGO criteria were used to assess the incidence and severity of early AKI. Factors influencing early AKI were determined using univariate and multiple logistic regression analysis. Between January 2016 and December 2018, Data from 128 critically ill burned patients were available for analysis. The median age was 44.9±16.8 years; 68.8% of the patients were male. The median TBSA% was 60 (IQR, 41.3-80%). According to the KDIGO criteria, 36 patients (28.3%) developed early AKI, as follows: stage 1 AKI, 69.4% (25/36); stage 2 AKI, 13.9% (5/36); and stage 3 AKI, 16.7% (6/36). The incidence of early AKI was associated with TBSA%, full-thickness TBSA%, abbreviated burn severity index on admission (ABSI), inhalation injury, mechanical ventilation, cardiovascular complications, and rhabdomyolysis. Multiple logistic regression analysis indicate that TBSA% (OR=0.224, p=0.007), full-thickness TBSA% (OR=0.254, p=0.014), ABSI (OR=18.326, p=0.009), and rhabdomyolysis (OR=24.036, p=0.000) were independent risk factors for the occurrence of early AKI. Significant factors influencing the severity of early AKI included full-thickness body surface area burns, electrical burns, and rhabdomyolysis. Full-thickness TBSA% (OR=1.437, p=0.041) and rhabdomyolysis (OR=5.401, p=0.035) are associated with mortality. The risk of death due to the occurrence of AKI was 5.407 in the Cox model adjusted for TBSA%, full-thickness body surface area burns, ABSI and rhabdomyolysis. Three patients died, all of whom had stage 3 AKI, accounting for 8.3% (3/36) of AKI patients. The death rate of stage 3 AKI who did and did not receive early RRT was 33.3% and 66.7%, respectively. Rhabdomyolysis is an independent risk factor for early AKI and closely related to the severity of early AKI in critically ill burned patients. Although with a high incidence of early AKI in severely burned patients, most of them are mild. Early adequate fluid resuscitation, timely and effective escharotomy, reducing the incidence and severity of rhabdomyolysis, most of them can achieve a relatively good prognosis.

Dysregulation of microRNA biogenesis in the small intestine after ethanol and burn injury

Ethanol exposure at the time of burn injury is a major contributor to post-burn pathogenesis. Many of the adverse effects associated with ethanol and burn injury are linked to an impaired intestinal barrier. The combined insult causes intestinal inflammation, resulting in tissue damage, altered tight junction expression, and increased intestinal permeability. MicroRNAs play a critical role in maintaining intestinal homeostasis including intestinal inflammation and barrier function. Specifically, miR-150 regulates inflammatory mediators which can contribute to gut barrier disruption. The present study examined whether ethanol and burn injury alter expression of microRNA processing enzymes (Drosha, Dicer, and Argonaute-2) and miR-150 in the small intestine. Male mice were gavaged with ethanol (~2.9g/kg) 4h prior to receiving a ~12.5% total body surface area full thickness burn. One or three days after injury, mice were euthanized and small intestinal epithelial cells (IECs) were isolated and analyzed for expression of microRNA biogenesis components and miR-150. Dicer mRNA and protein levels were not changed following the combined insult. Drosha and Argonaute-2 mRNA and protein levels were significantly reduced in IECs one day after injury; which accompanied reduced miR-150 expression. To further determine the role of miR-150 in intestinal inflammation, young adult mouse colonocytes were transfected with a miR-150 plasmid and stimulated with LPS (100ng/ml). miR-150 overexpression significantly reduced IL-6 and KC protein levels compared to vector control cells challenged with LPS. These results suggest that altered microRNA biogenesis and associated decrease in miR-150 likely contribute to increased intestinal inflammation following ethanol and burn injury.

Preclinical Evaluation of Flt3 Ligand to Improve T Cell Adaptive Immune Response During Sepsis

BackgroundSepsis is a leading cause of death in the United States. Severely burned patients are highly susceptible to opportunistic infections and sepsis, leading to multi‐organ failure and death. Studies by Hotchkiss and colleagues show that T cell dysfunction significantly contributes to impaired immune response during sepsis in non‐burn subjects. However, the changes in T cell adaptive immunity after burn wound sepsis have not been investigated in detail. We used a clinically relevant mouse model of burn wound infection to assess adaptive immune system function. Furthermore, we evaluated the cytokine, Fms‐like tyrosine kinase‐3 ligand (Flt3L), to improve T cell adaptive immunity post burn wound sepsis. Flt3L is known to stimulate the expansion of hemopoietic progenitors, particularly dendritic cells.Methods8–10 weeks old male BALB/c mice were subjected to 35% total body surface area full thickness burn and the wound was infected with Pseudomonas aeruginosa on day 4 post‐burn. Flow cytometry was used to characterize the cell counts and phenotype of CD4+ and CD8+ T and dendritic cells in spleen and wound draining lymph nodes. Flt3L (10 μg, i.p.) was administered daily for 4 days following burn injury.ResultsWound infection led to severe sepsis in the mice as evidenced by detection of bacteria in blood and lungs, and multi‐organ injury (increased markers of liver and kidney injury) on day 2 after infection and mortality rate of approximately 80% by seven days. We observed a significant decline (>80%) in blood absolute lymphocyte count and CD4+ and CD8+ T cell counts in the spleen and burn‐draining lymph nodes of wound infected mice as compared to non‐infected burn mice on day 2 post infection. Flt3L significantly attenuated the infection induced decline in CD4+ and CD8+ T cell counts in the spleen. Wound infection also caused a decline in the CD11c+ dendritic cell numbers in lymph nodes. Flt3L stimulated the expansion of both the splenic and lymph node dendritic cells and protected against the dendritic cell loss in the lymph nodes. Furthermore, wound infection caused an increase in the expression of Programmed Death‐Ligand 1 (PD‐L1) expression on dendritic cells, F4/80+ macrophages and Ly6C+ inflammatory monocytes in the spleen. PD‐L1 is known to interact with its binding partner PD‐1 on T cell surface leading to T cell inhibition. Flt3L attenuated the increase in PD‐L1 expression and thus indirectly improves T cell function.ConclusionBurn wound sepsis causes significant adaptive immune system dysfunction and Flt3L represents a novel therapeutic cytokine to protect T cell function during sepsis and merits further investigation.Support or Funding InformationSupported by NIH R01 GM66885

Regional variation in expression of pro-inflammatory mediators in the intestine following a combined insult of alcohol and burn injury

The intestine is segmented into functionally discrete compartments (duodenum, jejunum, ileum, and colon). The present study examined whether alcohol combined with burn injury differently influences cytokine levels in different parts of the intestine. Male mice were gavaged with alcohol (∼2.9 g/kg) 4 h prior to receiving a ∼12.5% total body surface area full thickness burn. Mice were sacrificed 1, 3, and 7 days after injury. The intestine segments (duodenum, jejunum, ileum, and colon) were harvested, homogenized, and analyzed for inflammatory mediators (IL-6, IL-18, and KC) using their respective ELISAs. KC levels were significantly increased in the jejunum, ileum, and colon following alcohol and burn injury as compared to shams. The increase in KC was ∼28-fold higher in the colon as compared to the levels observed in duodenum following alcohol and burn injury. Both IL-6 and IL-18 levels were significantly elevated in both the ileum and colon following the combined insult. There was a ∼7-fold increase in IL-6 levels in the colon as compared with the duodenum after the combined insult. Levels of IL-18 were increased by ∼1.5-fold in the colon as compared to the ileum following alcohol and burn injury. The data suggest that pro-inflammatory mediators are differentially expressed in the intestine following alcohol and burn injury.

The Role of Aryl Hydrocarbon Receptor in Interleukin-23-Dependent Restoration of Interleukin-22 Following Ethanol Exposure and Burn Injury

T-helper (Th)-17 lymphocytes play a crucial role in maintenance and regulation of gut immunity. Our laboratory has demonstrated that acute ethanol (EtOH) exposure before burn injury results in intestinal T cell suppression and enhanced bacterial translocation. To extend these studies, we examined the effects of EtOH exposure and burn injury on Th17 responses within intestinal lymphoid Peyer's patches (PP). We further investigated whether restitution of interleukin (IL)-23 enhances PP cell IL-17 and IL-22 after EtOH and burn injury. Male mice, approximately 25 g, were gavaged with EtOH (2.9 mg/kg) before receiving an approximately 12.5% total body surface area full thickness burn. One day postinjury, PP mixed cells were cultured in the presence of plate-bound anti-CD3/soluble anti-CD28 in the presence or absence of IL-23 for 48 hours. Supernatants were harvested for IL-17 and IL-22 levels. When combined with EtOH intoxication, burn injury significantly decreased IL-17 and IL-22, as compared with sham injury. IL-23 treatment successfully increased levels of IL-22 but not IL-17. This restoration was prevented when PP cells were treated with CH-223191, an aryl hydrocarbon receptor inhibitor. To further delineate the mechanism of differential IL-17 and IL-22 suppression, PP cells were treated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, which signal via protein kinase C (PKC) and calcium flux. Treatment with PMA and ionomycin significantly prevented the decrease in IL-17 but not IL-22 after EtOH exposure and burn injury. These findings suggest that IL-23-mediated restoration of IL-22 is aryl hydrocarbon receptor dependent, whereas IL-17 requires activation of protein kinase C and intracellular calcium signaling.

Procalcitonin in the Burn Unit and the Diagnosis of Infection

ObjectiveTo determine the usefulness of procalcitonin (PCT) in decision-making when faced with suspected infection in patients with extensive burns. StudyRetrospective, observational follow-up study. InstitutionBurn Unit of the Complexo Hospitalario Universitario A Coruña (CHUAC), Spain. Patients and methodWe included all patients admitted to the Unit from June 2011 to March 2012 with ≥20% total body surface area burned or ≥10% full-thickness body surface area burned with suspected infection (17 patients with 34 events of suspected infection). ResultsThe infections were confirmed in 16/34 episodes (47.1%), and documented in 44.1% (n=15). There were no statistically significant differences in the PCT figures at the time the infection was suspected between the cases with confirmed and unconfirmed infection (p=0.682). The PCT values showed no discriminative value for differentiating patients with SIRS from those with sepsis, severe sepsis and septic shock (area under ROC curve (AUC)=0.546; 95% CI: 0.326–0.766). No significant correlation was found between SOFA and PCT, although there were differences in the PCT values in the patients who had tissue hypoperfusion. ConclusionResults show that PCT is not a precise indicator of sepsis at the time of diagnosis. A correlation between PCT levels and hypoperfusion was observed.

Combined radiation and thermal injury induces a non-suppressive myeloid CD11b+ Gr1+ cell population (P4025)

Abstract Increasing sophistication of terrorist attacks and recent nuclear energy crises have amplified the interest in the immunobiology of combined radiation and burn injury (RCI). Burn is associated with immunosuppression and increased mortality with lower doses of ionizing radiation. Following trauma, putative myeloid derived suppressor cells (MDSCs; CD11b+Gr1+) have been described. We hypothesized that RCI-MDSCs display a suppressive phenotype and RCI will result in increased susceptibility to bacterial infection. C57BL/6 female mice underwent either a 20% total body surface area full thickness contact burn or sham procedure. All mice then received a single whole body dose of 5Gy γ-radiation. Mice were infected 14 days post injury with Pseudomonas aeruginosa intratracheally. Immune cells underwent apoptosis following RCI and infection, with CD11b+Gr1(Ly6C)+ cells being the predominant surviving cell type, which we isolated and cocultured 1:1 with untouched T cells. Surprisingly, T cells incubated with CD11b+Gr1(Ly6C)+ cells from RCI mice displayed greater proliferation, increased IFN-γ and decreased IL-10 production compared to MDSC from radiation-only mice. RCI mice were able to clear the P. aeruginosa infection significantly better than radiation-only mice. These data suggest that while RCI depletes immune cells, resistant CD11b+Gr1(Ly6C)+ cells represent a target population for modulation of bacterial clearance after injury.

Severe burn and disuse in the rat independently adversely impact body composition and adipokines

IntroductionSevere trauma is accompanied by a period of hypermetabolism and disuse. In this study, a rat model was used to determine the effects of burn and disuse independently and in combination on body composition, food intake and adipokines.MethodsMale rats were assigned to four groups 1) sham ambulatory (SA), 2) sham hindlimb unloaded (SH), 3) 40% total body surface area full thickness scald burn ambulatory (BA) and 4) burn and hindlimb unloaded (BH). Animals designated to the SH and BH groups were placed in a tail traction system and their hindlimbs unloaded. Animals were followed for 14 days. Plasma, urine, fecal and tissue samples were analyzed.ResultsSA had a progressive increase in body mass (BM), SH and BA no change and BH a reduction. Compared to SA, BM was reduced by 10% in both SH and BA and by 17% when combined in BH. Compared to SA, all groups had reductions in lean and fat body mass with BH being greater. The decrease in lean mass was associated with the rate of urinary corticosterone excretion. The loss in fat mass was associated with decreases in plasma leptin and adiponectin and an increase in ghrelin. Following the acute response to injury, BH had a greater food intake per 100 g BM. Food intake was associated with the levels of leptin, adiponectin and ghrelin.ConclusionsThe effects of the combination of burn and disuse in this animal model were additive, therefore in assessing metabolic changes with severe trauma both injury and disuse should be considered. Furthermore, the observed changes in adipokines, corticosterone and ghrelin provide insights for interventions to attenuate the hypermetabolic state following injury, possibly reducing catabolism and muscle loss and subsequent adverse effects on recovery and function.

Transcutaneous Carbon Dioxide Monitoring During Acute Respiratory Distress Syndrome Due to Smoke Inhalation and Burns

We evaluated the accuracy of continuous noninvasive transcutaneous carbon dioxide (tPCO2) monitoring utilizing the SenTec Digital Monitoring System in a model of ARDS due to smoke inhalation and burns.Subjectsanesthetized female Yorkshire pigs (47.4 ± 0.9 kg) received wood bark smoke inhalation injury and 40% total body surface area full thickness flame burn. A SenTec sensor heated to 43.5°C was used. Correlation of tPCO2 with arterial PaCO2 measured intermittently with i‐STAT blood gas analyzer.Resultsall animals developed ARDS at 23±2.08 hrs. Mean survival time was 51±14.9 hrs. A total of 88 paired measurements of PaCO2 and tPCO2 were performed. The mean overall bias between PaCO2 and tPCO2 under stable conditions (Bland‐Altman analysis (BAa)) was 0.75±5.34 mm Hg with overall correlation (R2 = 0.79, P<0.0001). Eighty‐nine percent of measurements were within the acceptable clinical range of agreement of ± 7.5mm Hg. This relationship deteriorated under hemodynamic instability with overall bias increasing to 17.3±18.5 mm Hg (BAa) and poor correlation (R2= 0.02, P=0.53) and only 33% of measurements were within the acceptable clinical range of agreement.ConclusionsTranscutaneous CO2 monitoring is a reliable surrogate for PaCO2 in the setting of severe lung injury and hemodynamic stability. Additional information must be considered during hemodynamic instability for accurate estimation of PaCO2.

Multidisciplinary team response to a mass burn casualty event: outcomes and implications

To describe the characteristics of patients with burn injury admitted to a major trauma hospital in Melbourne following the Black Saturday bushfires of 7 February 2009, and to provide a detailed analysis of the hospital's response to the crisis. A retrospective chart review of ambulance and hospital records of patients admitted to the Victorian Adult Burns Service (VABS) at The Alfred Hospital (The Alfred) following the bushfires. Patient characteristics and outcomes: age, sex, total and full thickness body surface area burnt, type and site of burn, hospital and intensive care unit length of stay (LOS) and receipt of standard burn care practices. Estimated glomerular filtration rate, theatre time and LOS data for the bushfire cohort compared with corresponding data for historical cohorts from VABS and from a similar institution in New Zealand. Nineteen patients were admitted to VABS over the first 48 hours after the bushfires. Of these, nine patients were subsequently admitted to The Alfred's intensive care unit. Most patients (74%) were men with a mean age of 52.7 years (SD, 12.4 years). Seventeen patients (89%) underwent at least one surgical procedure, which resulted in 4355 minutes of theatre time for the bushfire cohort in the first week. Hospital LOS was similar for the bushfire and New Zealand cohorts. Compared with the VABS historical cohort, there was a higher incidence of abnormal renal function among the bushfire cohort patients. Although relatively few patients with severe burns were admitted to VABS, significant increases in resource allocation were required to manage them in terms of additional theatre time, consumables and staffing. The experience of VABS may aid planning for future mass burns casualty events.

Limb intracompartmental sepsis in burn patients associated with occult infection

Background Intracompartmental sepsis (IS) is a rare complication in burn patients. IS presents in patients with inadequate perfusion of intracompartmental tissues with subsequent ischaemic necrosis and infection. Contributing factors include high-volume resuscitation, delayed escharotomies and previous bacteraemias. We describe the profile of a series of patients who developed IS in our Intensive Care Burn Unit (ICBU). Methods We carried out a retrospective chart review of patients admitted to an ICBU over a 5-year period. Results Seven patients of 659 admissions (1.0%) developed IS involving the extremities. Diagnosis was based on the identification of purulent drainage and local swelling associated with signs of sepsis of unknown origin. Total body surface area (TBSA) burned averaged 67.4% and full-thickness body surface area (FTBSA) burned averaged 48.4%. All patients were sedated and mechanically ventilated. The first 24-h fluid requirements averaged 6.0 ml kg –1 per %TBSA burn (range 3.5–7.0 ml kg –1 per %TBSA). Escharotomies were performed in five patients within the first 24 h of admission. Median time of diagnosis of IS was 23 days from admission (range 11–45 days). Four patients developed bacteraemia caused by the same microorganism infecting the soft tissue. In five cases, the infecting microorganism had previously colonised the overlying burned skin. Three patients required amputation of the affected limb. Conclusion IS is a devastating infectious complication which appears late after large burns. Predisposing factors include high-volume resuscitation, delayed escharotomies, colonisation of the overlying skin and previous bacteraemias. Earlier diagnosis and management are needed to attain a better outcome.

A model for predicting mortality among critically ill burn victims

Objective To develop a model for predicting mortality among burn victims. Methods All casualties admitted to our intensive care burn unit (ICBU) with a diagnosis of thermal or inhalation injury were studied. Age, total and full-thickness body surface area (BSA) burned, presence of inhalation injury, gender, mechanism of injury, delay to ICBU admission and mechanical ventilation during the first 72 h were recorded. The 851 participants were randomly divided into derivation (671) and validation (180) sets. From univariate and multivariate logistic regression analyses a mortality predictive equation was derived. Results Mortality was 17.6%. In univariate analysis, all variables were significantly associated with mortality except mechanism of injury and delay to ICBU admission. In multivariate analysis, age, total and full-thickness BSA burned, female gender and early mechanical ventilation were independently associated with mortality. Conclusions We propose a mortality predictive equation for burned victims. In this model, MV and not inhalation injury is a mortality risk factor.

Poster 45: Functional Outcome in a Patient with 92 Percent Total Body Surface Area Full-Thickness Burns: A Case Report

Setting: Acute inpatient rehabilitation unit. Patient: 31-year-old man without medical history who sustained 92% full-thickness total body surface area (TBSA) burns secondary to flame-related injury. Case Description: The patient presented to the inpatient rehabilitation unit after surviving 92% TBSA full-thickness burns from a flame-related injury at work. During the patient's 4 month stay in the burn unit, he required pressor support and mechanical ventilation. He also underwent multiple skin grafts and debridements secondary to his severe burns. He was transferred to the acute inpatient rehabilitation unit 4 months after his original injury with a tracheostomy and percutaneous gastric tube. Assessment/Results: On admission to the rehabilitation unit, the patient was nonambulatory and was at a maximum assist level for transfers and self-care. He also remained nothing by mouth with bolus tube feeds. His wounds were aggressively managed and required dressing changes with each nursing shift. The patient was followed closely by all disciplines, including physical and occupational therapy, speech/language/pathology, psychology, wound care, and respiratory therapy. During his 57-day stay in the rehabilitation unit, the patient made significant progress. The patient was able to ambulate at a modified independent level within 4 weeks. Self-care skills improved slowly secondary to upper-extremity contractures. On discharge, the patient was minimum assist for upper-extremity dressing, set-up for feeding, and maximum assist for toileting and lower body dressing. Dysphagia improved and was upgraded to a mechanical soft diet with thin liquids on discharge to home. Conclusions: Survival rates for patients sustaining greater than 90% TBSA are low. According to the National Burn Repository Report of 2006, 74 cases in the 30 to 39 year-old age group were reported for full-thickness burns of 90% or greater, and of those 74 cases, 61 patients died. Current literature reveals that it is rare for a patient to sustain and survive greater than 90% TBSA full-thickness burn injury. Comprehensive inpatient rehabilitation is vital to burn-injured patients, providing a multi-disciplinary approach for patients to regain function and independence.

The Neuropeptide Substance P Is a Critical Mediator of Burn-Induced Acute Lung Injury

The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses alter neural activity. Therefore, this study aimed to investigate the effect of local burn injury on inducing distant organ pulmonary SP release and its relevance to lung injury. Our results show that burn injury in male BALB/c mice subjected to 30% total body surface area full thickness burn augments significant production of SP, preprotachykinin-A gene expression, which encodes for SP, and biological activity of SP-neurokinin-1 receptor (NK1R) signaling. Furthermore, the enhanced SP-NK1R response correlates with exacerbated lung damage after burn as evidenced by increased microvascular permeability, edema, and neutrophil accumulation. The development of heightened inflammation and lung damage was observed along with increased proinflammatory IL-1beta, TNF-alpha, and IL-6 mRNA and protein production after injury in lung. Chemokines MIP-2 and MIP-1alpha were markedly increased, suggesting the active role of SP-induced chemoattractants production in trafficking inflammatory cells. More importantly, administration of L703606, a specific NK1R antagonist, 1 h before burn injury significantly disrupted the SP-NK1R signaling and reversed pulmonary inflammation and injury. The present findings show for the first time the role of SP in contributing to exaggerated pulmonary inflammatory damage after burn injury via activation of NK1R signaling.

Burn-Related Metabolic and Signaling Changes in Rat Brain

Postburn alterations in the morphology and metabolism of brain tissue have been previously reported. It was demonstrated in our previous study that thermal injury decreased glucose usage in rat brain during the ebb phase. The cellular and molecular signaling events that trigger the pathophysiologic alterations, however, have not yet been characterized. In the present report, the authors have examined the effect of burn injury on mitogen-activated protein kinases (MAPKs) activities and insulin signaling in the brain tissue. Rats were subjected to 50% total body surface area full thickness scald injury. Brain samples were collected at 6 hours after injury. Tissue lysates were analyzed for MAPKs activities, insulin receptor substrate (IRS)-1 expression, and Akt activity which were determined by western blot and immunoprecipitation. Burn injury stimulated the stress-responsive components, SAPK/JNK, p38 MAP kinase and p44/42 MAP kinase, and increased IRS-1 expression and Akt activity. There was no change, however, on the phosphorylation of Ser307 of IRS-1 in brain tissue. The present data is consistent with the hypothesis that activation of the three major MAPKs pathways appears to be events involved in the mechanisms of burn injury induced insulin resistance and encephalopathy. Changes in signal transduction pathways in the brain after burn injury provide the underlying molecular mechanism of neurologic abnormalities (burn encephalopathy) that occur in burn patients.

The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats

This study was designed to assess intestinal drug transport via transcellular absorption and intestinal P-glycoprotein content following thermal injury in rats using propranolol as a marker substrate. Male, Sprague Dawley rats ( n=30) underwent either a 30% total body surface area full thickness burn or sham treatment. Twenty-four hours later, animals were anesthetized, underwent laparotomy and the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing [ 3 H] propranolol. Following euthanasia, jejunal tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in jejunal integrity were observed following thermal injury; however, no significant differences in the absorption characteristics of propranolol following thermal injury were observed. Mean effective permeability of propranolol was 5.67±1.79 and 5.85±1.67 cm/ s×10 −5 for burn and sham groups, respectively ( P>0.05). P-glycoprotein and villin content in the jejunum were significantly decreased in burn animals. The transcellular transport of propranolol is unaffected 24 h following thermal injury in rats, despite alterations in intestinal P-glycoprotein content. The decrease in P-glycoprotein and villin content in thermally injured animals may reflect loss of mature enterocytes at the villus tips.

Effect of bombesin on gut mucosal impairment after severe burn.

Severe cutaneous bum alters gut epithelial homeostasis. In previous studies, treatment with bombesin decreased mucosal atrophy and improved maintenance of gut mucosal integrity after severe burn. Our current hypothesis is that bombesin reduces burn-induced gut impairment by decreasing gut epithelial cell death. Fifty-four adult male Fisher-344 rats were randomly assigned to three groups: control, sham burn (I), burn (II), and burn + bombesin (III). Animals in groups II and III received a 60% total body surface area full thickness scald burn, and the treatment group (III) received bombesin subcutaneously (10 microg/kg, every 8 h) beginning immediately before the experiment. The proximal small bowel was harvested at 12 and 72 h after burn with measurement of wet and dry weight, mucosal weight, and protein content, and a 1-cm length of proximal end was excised and fixed in fomalin for histological and immunohistochemical observation. Data are expressed as means +/- SEM. Statistical analysis was by done by analysis of variance (significance at P < 0.05). Bombesin treatment attenuated mucosal atrophy demonstrated by restoration of the mucosal weight, mucosal protein content, and maintenance of mucosal height and total mucosal epithelial cell count. Gut epithelial cell apoptosis was, at least in part, inhibited by bombesin compared with a significant increase of gut cell apoptosis at 12 h after burn. Gut epithelial proliferation was not affected. Bombesin diminished burn-induced gut mucosal atrophy and gut epithelial cell apoptosis, suggesting that bombesin treatment may play an important role in the recovery of gut impairment after severe burn.

Recombinant human growth hormone modulates the hepatic acute-phase response and P-selectin in burned rats

The purpose of this study was to determine the effect of recombinant human growth hormone (rhGH) on serum constitutive proteins, cytokines, P-selectin, and insulin-like growth factor (IGF-1) in the thermally injured rats. Sprague–Dawley rats (64 males) were given 30% total body surface area full thickness scald burn. They were randomly divided to receive either 2.5 mg/kg per day im rhGH or saline (control). Rats were sacrified on postburn days 1, 2, 5, and 7, and serum constitutive proteins, cytokines, P-selectin, and IGF-1 levels were measured. Serum IGF-1 levels were increased on days 2, 5, or 7 after burn in rhGH-treated rats compared with controls ( P<0.001, <0.01 and <0.001, respectively). Serum transferrin and albumin levels were increased on days 7 after burn in rhGH-treated rats compared with controls ( P<0.05). The cytokines increased after thermal injury. The rhGH decreased serum levels of tumor necrosis factor-α on postburn days 1 compared with controls ( P<0.001). Serum levels of interleukin-1 were decreased on days 1 and 2 after burn in rhGH treated rats compared with controls ( P<0.001, <0.01, respectively). Rats receiving rhGH showed significantly increased P-selectin levels at 5 and 7 postburn days compared with controls ( P<0.001). Our data indicate that rhGH, given after thermal injury, increased albumin, transferrin, IGF-1, and P-selectin levels and decreased serum tumor necrosis factor-α and interleukin-1 levels.