Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Morbidity and survival probability in burn patients in modern burn care.

OBJECTIVE: Characterizing burn sizes that are associated with an increased risk of mortality and morbidity is critical because it would allow identifying patients who might derive the greatest benefit from individualized, experimental, or innovative therapies. Although scores have been established to predict mortality, few data addressing other outcomes exist. The objective of this study was to determine burn sizes that are associated with increased mortality and morbidity after burn. DESIGN AND PATIENTS: Burn patients were prospectively enrolled as part of the multicenter prospective cohort study, Inflammation and the Host Response to Injury Glue Grant, with the following inclusion criteria: 0-99 years old, admission within 96 hours after injury, and more than 20% total body surface area burns requiring at least one surgical intervention. SETTING: Six major burn centers in North America. MEASUREMENTS AND MAIN RESULTS: Burn size cutoff values were determined for mortality, burn wound infection (at least two infections), sepsis (as defined by American Burn Association sepsis criteria), pneumonia, acute respiratory distress syndrome, and multiple organ failure (Denver 2 score>3) for both children (<16 yr) and adults (16-65 yr). Five hundred seventy-three patients were enrolled, of which 226 patients were children. Twenty-three patients were older than 65 years and were excluded from the cutoff analysis. In children, the cutoff burn size for mortality, sepsis, infection, and multiple organ failure was approximately 60% total body surface area burned. In adults, the cutoff for these outcomes was lower, at approximately 40% total body surface area burned. CONCLUSIONS: In the modern burn care setting, adults with over 40% total body surface area burned and children with over 60% total body surface area burned are at high risk for morbidity and mortality, even in highly specialized centers.

Benchmarking outcomes in the critically injured burn patient.

OBJECTIVE: To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers. BACKGROUND: Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries. METHODS: We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care. RESULTS: Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 ± 18.3 for adults and 57.8 ± 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant. CONCLUSIONS: This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions.

Mild obesity is protective after severe burn injury.

OBJECTIVE: To assess the impact of obesity on morbidity and mortality in severely burned patients. BACKGROUND: Despite the increasing number of people with obesity, little is known about the impact of obesity on postburn outcomes. METHODS: A total of 405 patients were prospectively enrolled as part of the multicenter trial Inflammation and the Host Response to Injury Glue Grant with the following inclusion criteria: 0 to 89 years of age, admitted within 96 hours after injury, and more than 20% total body surface area burn requiring at least 1 surgical intervention. Body mass index was used in adult patients to stratify according to World Health Organization definitions: less than 18.5 (underweight), 18.5 to 29.9 (normal weight), 30 to 34.9 (obese I), 35 to 39.9 (obese II), and body mass index more than 40 (obese III). Pediatric patients (2 to ≤18 years of age) were stratified by using the Centers for Disease Control and Prevention and World Health Organization body mass index-for-age growth charts to obtain a percentile ranking and then grouped as underweight (<5th percentile), normal weight (5th percentile to <95th percentile), and obese (≥95th percentile). The primary outcome was mortality and secondary outcomes were clinical markers of patient recovery, for example, multiorgan function, infections, sepsis, and length of stay. RESULTS: A total of 273 patients had normal weight, 116 were obese, and 16 were underweight; underweight patients were excluded from the analyses because of insufficient patient numbers. There were no differences in primary and secondary outcomes when normal weight patients were compared with obese patients. Further stratification in pediatric and adult patients showed similar results. However, when adult patients were stratified in obesity categories, log-rank analysis showed improved survival in the obese I group and higher mortality in the obese III group compared with obese I group (P < 0.05). CONCLUSIONS: Overall, obesity was not associated with increased morbidity and mortality. Subgroup analysis revealed that patients with mild obesity have the best survival, whereas morbidly obese patients have the highest mortality. (NCT00257244).

Glutathione: a redox signature in monitoring EPI-743 therapy in children with mitochondrial encephalomyopathies.

BACKGROUND: Genetically defined Leigh syndrome (LS) is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. Although mitochondrial dysfunction has clearly been associated with oxidative stress, few studies have specifically examined Leigh syndrome patients' blood glutathione levels. In this study, we analyzed the balance between oxidized and reduced glutathione in lymphocytes of 10 patients with genetically confirmed LS and monitored the effects of glutathione status following 6 months of treatment with EPI-743, a novel redox therapeutic. METHODS: Lymphocytes were obtained from blood samples of 10 children with a genetically confirmed diagnosis of LS and in 20 healthy subjects. Total, reduced, oxidized and protein-bound glutathione levels were determined by HPLC analysis. Erythrocyte superoxide dismutase and glutathione peroxidase enzyme activities were measured by spectrophotometric assays. Plasma total thiols, carbonyl contents and malondialdehyde were assessed by spectrophotometric and fluorometric assays. RESULTS: A significant impairment of all glutathione forms was detected in patients, including a profound decrease of total and reduced glutathione (GSH) associated with high levels of all oxidized glutathione forms (GSSG+GS-Pro; OX). These findings negatively correlated with the glutathione peroxidase activity, which underwent a significant decrease in patients. After treatment with EPI-743, all patients showed a significant increase in reduced glutathione levels and 96% decrease of OX/GSH ratio. CONCLUSIONS: The data presented here strongly support glutathione as a "redox blood signature" in mitochondrial disorders and its use as a clinical trial endpoint in the development of mitochondrial disease therapies.

EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome.

BACKGROUND: Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. METHODS: A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. RESULTS: Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. CONCLUSIONS: In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome.

Epidemiology of upper extremity replantation surgery in the United States.

PURPOSE: Replantation remains an important technique in the management of hand trauma. Given the resources necessary for a successful replantation program, regionalization of replantation care may ultimately be required. The purposes of this study were to analyze the geographic distribution of upper extremity replant procedures, analyze factors of patients undergoing replantation, and characterize the facilities performing these procedures. METHODS: We performed a cohort study using the National Inpatient Sample of the Healthcare Cost and Utilization Project from 2001, 2004, and 2007. Patients with an upper extremity amputation were defined, and a subgroup of patients undergoing replantation was delineated. We analyzed patient demographics and injury characteristics and characteristics of treating facilities. RESULTS: A total of 9,407 patients were treated for upper extremity amputation, 1,361 of whom underwent replantation. Mean age of patients undergoing replantation was 36 years (range, 0-86 y), compared with 44 years (range, 0-104 y) in patients not undergoing replantation. Hospital charges (P < .001) and length of stay (P < .001) were significantly higher for patients with replantations versus those without replantations. Patients treated at teaching facilities were more likely to undergo replantation than those at a non-teaching facility (19% replantation rate at teaching hospitals vs 7% at non-teaching). Large hospitals and urban hospitals were more likely to perform replantation. Self-pay, Medicare, and Medicaid patients all had lower replantation rates than patients with other payer status. CONCLUSIONS: Patients who undergo replantation are younger, incur higher hospital charges, and have longer hospital stays compared with patients who do not undergo replantation. Treatment at large, urban, and teaching facilities is associated with higher replantation rates. Payer status appears to have some bearing on replantation rates. Further studies are needed to better elucidate the relationship between patient and injury characteristics, treatment location, and outcomes, to adequately distribute the finite resources for replantation. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and Decision Analysis IV.

Fournier's gangrene: management and mortality predictors in a population based study.

PURPOSE: The Fournier's gangrene literature comes almost exclusively from tertiary referral centers. We used a population based database to evaluate variations in management and outcomes. MATERIALS AND METHODS: Inpatients with Fournier's gangrene who underwent surgical débridement or died were identified from select states in the State Inpatient Databases. Multivariate logistic regression analysis was done to evaluate patient and hospital related predictors of mortality. RESULTS: We identified 1,641 males with Fournier's gangrene treated at a total of 593 hospitals. At teaching hospitals more Fournier's gangrene cases were treated per year, and more surgical procedures, débridements and supportive care were reported. Patients treated at teaching hospitals had longer length of stay, greater hospital charges and a higher case fatality rate. Patient related predictors of mortality were increasing age (adjusted OR 4.0 to 15.0), Charlson comorbidity index (adjusted OR 1.20 per additional comorbidity), preexisting conditions, ie congestive heart failure (adjusted OR 2.1), renal failure (adjusted OR 3.2) and coagulopathy (adjusted OR 3.4), and hospital admission via transfer (adjusted OR 1.9), after adjusting for hospital factors and Fournier's gangrene experience. Teaching hospitals had higher mortality due primarily to more acutely ill patients (adjusted OR 1.9). Hospitals where more than 1 Fournier's gangrene case per year were treated had 42% to 84% lower mortality after adjusting for patient age, race, Charlson comorbidity index and admission via transfer (p <0.0001). CONCLUSIONS: Teaching and nonteaching hospitals differ substantially in the populations, case definitions, and severity and management of Fournier's gangrene. Hospitals where more patients with Fournier's gangrene were treated had lower mortality rates, supporting the rationale for regionalized care for this rare disease.

Fournier's Gangrene: population based epidemiology and outcomes.

PURPOSE: Case series have shown a Fournier's gangrene mortality rate of 20% to 40% with an incidence of as high as 88% in some studies. Because to our knowledge there are no population based data, we used a national database to investigate the epidemiology of Fournier's gangrene. MATERIALS AND METHODS: We used the State Inpatient Databases, the largest hospital based database available in the United States, which includes 100% of hospital discharges from participating states. Inpatients diagnosed with Fournier's gangrene (ICD-9 CM 608.83) who underwent genital/perineal débridement or died in the hospital were identified from 13 participating states in 2001 and from 21 in 2004. Population based incidence, regional trends and case fatality rates were estimated. RESULTS: We identified 1,641 males and 39 females with Fournier's gangrene. Cases represented less than 0.02% of hospital admissions. The overall incidence was 1.6/100,000 males, which peaked in males who were 50 to 79 years old (3.3/100,000) with the highest rate in the South (1.9/100,000). The overall case fatality rate was 7.5%. Patients with Fournier's gangrene were rarely treated at hospitals (mean +/- SD 0.6 +/- 1.2 per year, median 0, range 0 to 23). Overall 0 to 4 and 5 or greater cases were treated at 66%, 17%, 10%, 4%, 1% and 1% of hospitals, respectively. CONCLUSIONS: Patients with Fournier's gangrene are rarely treated at most hospitals. The population based mortality rate of 7.5% was substantially lower than that reported in case series from tertiary care centers.

Geographic access to burn center hospitals.

CONTEXT: The delivery of burn care is a resource-intensive endeavor that requires specialized personnel and equipment. The optimal geographic distribution of burn centers has long been debated; however, the current distribution of centers relative to geographic area and population is unknown. OBJECTIVE: To estimate the proportion of the US population living within 1 and 2 hours by rotary air transport (helicopter) or ground transport of a burn care facility. DESIGN AND SETTING: A cross-sectional analysis of geographic access to US burn centers utilizing the 2000 US census, road and speed limit data, the Atlas and Database of Air Medical Services database, and the 2008 American Burn Association Directory. MAIN OUTCOME MEASURE: The proportion of state, regional, and national population living within 1 and 2 hours by air transport or ground transport of a burn care facility. RESULTS: In 2008, there were 128 self-reported burn centers in the United States including 51 American Burn Association-verified centers. An estimated 25.1% and 46.3% of the US population live within 1 and 2 hours by ground transport, respectively, of a verified burn center. By air, 53.9% and 79.0% of the population live within 1 and 2 hours, respectively, of a verified center. There was significant regional variation in access to verified burn centers by both ground and rotary air transport. The greatest proportion of the population with access was highest in the northeast region and lowest in the southern United States. CONCLUSION: Nearly 80% of the US population lives within 2 hours by ground or rotary air transport of a verified burn center; however, there is both state and regional variation in geographic access to these centers.

Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy.

BACKGROUND: Mitochondrial disease is a family of genetic disorders characterized by defects in the generation and regulation of energy. Epilepsy is a common symptom of mitochondrial disease, and in the vast majority of cases, refractory to commonly used antiepileptic drugs. Ferroptosis is a recently-described form of iron- and lipid-dependent regulated cell death associated with glutathione depletion and production of lipid peroxides by lipoxygenase enzymes. Activation of the ferroptosis pathway has been implicated in a growing number of disorders, including epilepsy. Given that ferroptosis is regulated by balancing the activities of glutathione peroxidase-4 (GPX4) and 15-lipoxygenase (15-LO), targeting these enzymes may provide a rational therapeutic strategy to modulate seizure. The clinical-stage therapeutic vatiquinone (EPI-743, α-tocotrienol quinone) was reported to reduce seizure frequency and associated morbidity in children with the mitochondrial disorder pontocerebellar hypoplasia type 6. We sought to elucidate the molecular mechanism of EPI-743 and explore the potential of targeting 15-LO to treat additional mitochondrial disease-associated epilepsies. METHODS: Primary fibroblasts and B-lymphocytes derived from patients with mitochondrial disease-associated epilepsy were cultured under standardized conditions. Ferroptosis was induced by treatment with the irreversible GPX4 inhibitor RSL3 or a combination of pharmacological glutathione depletion and excess iron. EPI-743 was co-administered and endpoints, including cell viability and 15-LO-dependent lipid oxidation, were measured. RESULTS: EPI-743 potently prevented ferroptosis in patient cells representing five distinct pediatric disease syndromes with associated epilepsy. Cytoprotection was preceded by a dose-dependent decrease in general lipid oxidation and the specific 15-LO product 15-hydroxyeicosatetraenoic acid (15-HETE). CONCLUSIONS: These findings support the continued clinical evaluation of EPI-743 as a therapeutic agent for PCH6 and other mitochondrial diseases with associated epilepsy.

Japanese Leigh syndrome case treated with EPI-743.

BACKGROUND: Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. CASE: At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I. RESULTS: At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time. CONCLUSION: Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome.

Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.

AIM: To evaluate the safety and clinical effects of EPI-743 in Friedreich's ataxia patients. EPI-743 is a compound that targets oxidoreductase enzymes essential for redox control of metabolism. METHODS: We conducted a multicenter trial that evaluated EPI-743 during a 6-month placebo-controlled phase, followed by an 18-month open-label phase. End points included low-contrast visual acuity and the Friedreich's Ataxia Rating Scale. RESULTS/CONCLUSION: EPI-743 was demonstrated to be safe and well tolerated. There were no significant improvements in key end points during the placebo phase. However, at 24 months, EPI-743 treatment was associated with a statistically significant improvement in neurological function and disease progression relative to a natural history cohort (p < 0.001).

Assets and liabilities of the Burn Model System data model: a comparison with the National Burn Registry.

OBJECTIVES: To determine whether the Burn Model System (BMS) population is representative of the larger burn population and to investigate threats to internal and external validity in a multicenter longitudinal database of severe burns. DESIGN: Cohort data for the BMS project have been collected since 1994. Follow-up data have been collected at 6, 12, and 24 months postburn. The demographic and burn characteristics of the BMS population were compared with those of patients in the National Burn Registry (NBR). SETTING: The BMS, which collected data for these analyses from 5 regional burn centers in the United States, and the NBR dataset, which is a registry of information collected through the Trauma Registry of the American College of Surgeons and includes data from 70 hospitals in the United States and Canada. PARTICIPANTS: BMS study participants were severely burned patients treated at 1 of the 5 participating burn centers. We compared the BMS population with that of the NBR both in total and filtered to include only patients with comparable injuries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Comparable demographic and burn characteristics contained in both the NBR and the 5-center BMS longitudinal database and baseline and follow-up distributions of demographic variables and burn characteristics in the BMS database. RESULTS: Although minor deviations in demographic distributions were found between the BMS and NBR and between discharge and follow-up populations, our results show that the BMS population sample is internally and externally valid and is adequate for answering research questions. CONCLUSIONS: Cohort studies examining long-term outcomes have the potential flaw of using a nonrepresentative study population. The BMS population was found to be sufficiently representative, but future analyses will require cautious and purposeful application of statistical adjustment strategies.

Surgical management of acute necrotizing lung infections.

BACKGROUND: Surgical resection for acute necrotizing lung infections is not widely accepted due to unclear indications and high risk. OBJECTIVE: To review results of resection in the setting of acute necrotizing lung infections. METHODS: A retrospective review of patients who underwent parenchymal resection between January 1, 2000, and January 1, 2006, for management of necrotizing pneumonia or lung gangrene. RESULTS: Thirty-five patients underwent resection for lung necrosis. At the time of consultation, all patients presented with pulmonary sepsis, and also had the following: empyema (n = 17), hemoptysis (n = 5), air leak (n = 7), septic shock requiring pressors (n = 8) and inability to oxygenate adequately (n = 7). Twenty-four patients were ventilated preoperatively. Eleven patients had frank lobar gangrene, and the other patients had combinations of necrotizing pneumonia and abscesses. In 10 patients, preresection procedures were performed, including percutaneous drainage of an abscess (n = 4), thoracoscopic decortication (n = 4) and open decortication (n = 2). Procedures included pneumonectomy (n = 4), lobectomy (n = 18), segmentectomy (n = 2), wedge resection (n = 4) and debridement (n = 7). There were three (8.5%) postoperative deaths--two due to multiple organ failure and one due to anoxic brain injury. All patients not ventilated preoperatively were weaned from ventilatory support within three days. Of those ventilated preoperatively, three died, while four remained chronically ventilator dependent. CONCLUSIONS: Surgical resection for necrotizing lung infections is a reasonable option in patients with persistent sepsis who are failing medical therapy. Ventilated patients have a worse prognosis but can still be candidates for resection. Patients who are hemodynamically unstable appear to have better outcomes if they can be stabilized before resection.

An outcome analysis of patients transferred to a regional burn center: transfer status does not impact survival.

BACKGROUND: Optimal burn care is provided at specialized burn centers. Given the geographic location of these centers, many burn patients receive initial treatment at local emergency departments prior to transfer. The purpose of this study was to determine whether patients transferred from other facilities have worse outcomes than those admitted directly from the field. STUDY DESIGN: A retrospective cohort study was performed comparing the outcomes of patients admitted to our burn center directly from the field with patients requiring transfer from a preliminary care facility. The outcomes of interest were mortality, length of stay, length of stay/TBSA burned, number of operations and hospital charges. Poisson regression or Cox proportional hazards model was used to evaluate differences in outcomes after adjusting for potential confounders. RESULTS: From 2000 to 2003 a total of 1877 patients were admitted to our burn center and 953 (51%) were transferred from a preliminary care facility. No difference (p<0.05) was found in length of stay, number of operations, hospital charges and mortality between the two cohorts. CONCLUSIONS: This study demonstrates that patients transferred to a regional burn center from local hospitals have equivalent mortality, length of stay and hospital charges as those admitted directly from the field.

Propranolol Dosing Practices in Adult Burn Patients: Implications for Safety and Efficacy.

Studies in children with burn injuries have demonstrated that propranolol improves metabolism and reduces muscle protein wasting. However, safety and efficacy in adults are less well established than in children. The purpose of this study was to determine safety of propranolol use in adult patients with burn injuries. Medical records were reviewed for burn-injured adults receiving propranolol. Patients between 18 and 65 years old and with ≥20% TBSA burn were included. Fifty-four patients met the criteria with mean age of 37 years and mean burn size of 38% TBSA. Propranolol dosages ranged from 0.1 to 3.8 mg/kg/day, with an average maximum dosage of 0.61 mg/kg/day. Mean heart rate decreased by 25% during 4 weeks. Seventy-two percent of patients experienced at least one episode of hypotension and 15% experienced bradycardia. Propranolol doses were most frequently held for low blood pressure; 32% of patients had at least one dose held for hypotension. This retrospective analysis suggests that modest dosing of propranolol results in frequent episodes of hypotension or bradycardia. Our data suggest that adults do not tolerate the higher doses reported in a pediatric population. Despite potential beneficial anti-catabolic effects of propranolol, burn care providers must recognize potential iatrogenic hemodynamic effects of this intervention. Our data support the need for prospective multicenter studies to delineate the safety and efficacy of propranolol in adult burn-injured patients.

Management of facial burns with a collagen/glycosaminoglycan skin substitute-prospective experience with 12 consecutive patients with large, deep facial burns.

Management of deep facial burns remains one of the greatest challenges in burn care. We have developed a protocol over the past 20 years for management of facial burns that includes excision and coverage with thick autograft. However, the results were not perfect. Deformities of the eyelids, nose and mouth as well as the prominence of skin graft junctures demonstrated the need to explore novel approaches. Integra has been used with success in the management of burns of the trunk and extremities. The purpose of this study was to prospectively evaluate the aesthetic outcome of the use of Integra for deep facial burns. Twelve consecutive patients underwent excision of large, deep facial burns and placement of Integra. Integra provides excellent color and minimally visible skin graft junctures. The texture is good but not as supple as thick autograft. Integra is not well suited for use in the coverage of eyelid burns due to the need to wait 2 weeks for adequate vascularization. In summary, thick autograft remains the gold standard for deep facial burns. However, for patients with extensive burns and limited donor sites, Integra provides an acceptable alternative.

Patterns of grease burn injury: development of a classification system.

Grease burns occur commonly in the home during food preparation. It has been our observation that grease burns follow a particular pattern of injury. The purpose of this study was to review our institutional experience in the management of these burns to develop a classification scheme. We performed a retrospective review of patients admitted to our burn center with grease burns. Subjects were identified through our database and their charts were reviewed with particular attention to burn distribution, TBSA and need for grafting. We excluded workplace burns and children under the age of six. A total of 249 patients who fit the above criteria were admitted with grease burns to our burn center from 1993 to 2003. The sequence of events leading to burn and its distribution followed a consistent pattern. The majority of patients (86%) had an isolated upper extremity burn or upper extremity burn in combination with a face, trunk or lower extremity burn. Forty percent of patients required at least one excision and grafting procedure. Grease burns associated with cooking at home follow predictable patterns of injury. Based on these patterns we proposed a classification system for domestic grease burns.

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar.

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.