Apoptosis and Necrosis in the Ischemic Zone Adjacent to Third Degree Burns

Objectives:  Burns are characterized by a central zone of necrosis surrounded by a zone of potentially reversible ischemia. The authors explored the contribution of necrosis and apoptosis to cell death in the zone of ischemia.
Methods:  A previously established rat contact thermal injury model that utilizes a brass comb to produce four distinctive burns sites separated by three "interspaces" of unburned skin was used. The interspaces represent the zone of stasis or ischemia while the burn sites represent the zone of coagulation. With this model, most unburned interspaces progress to necrosis over 2 to 3 days. Full-thickness 3-mm biopsies were obtained from the interspaces, burns, and normal skin controls at 30 minutes, 24 hours, and 48 hours after injury. Slides were stained with hematoxylin and eosin as well as activated cleaved caspase-3 (CC3a) for evidence of apoptosis and high-mobility group box 1 (HMGB1) for evidence of necrosis.
Results:  Necrosis was not seen at 30 minutes, but was found in a large number of cells within the epidermis, sebaceous glands, and follicles at 24 and 48 hours. Faint nuclear CC3a staining indicative of apoptosis was present in a minority of cells within the epidermis, dermal fibroblasts, dermal follicles, and dermal sebaceous glands at 30 minutes and to a lesser degree at 24 and 48 hours.
Conclusions:  Both early apoptosis and delayed necrosis are present in the zone of ischemia, contributing to injury progression. Necrosis appears to play a larger role than apoptosis in injury progression in the comb burn model.     

Reepithelialization of mid-dermal porcine burns after rapid enzymatic debridement with Debrase?

Reepithelialization of mid-dermal burns is delayed by the presence of a layer of necrotic eschar. The authors hypothesized that rapid selective debridement using an enzymatic bromelain-based preparation, Debrase?, would speed reepithelialization. Forty mid-dermal burns (2.5 × 2.5 cm) were created on the back and flanks of two anesthetized domestic pigs (25 kg) using an aluminum bar (150 g) preheated in hot water (80°C) and applied for 20 seconds. The burns were randomized to a 4-hour topical application of Debrase? (n = 20) or its vehicle (n = 20) followed by daily application of a petrolatum-based triple antibiotic. Wounds were visualized and photographed daily for evidence of reepithelialization. Reepithelialization was considered complete when the entire wound was opaque and dry when blotted with tissue paper. 4-mm full-thickness biopsies were obtained for histological analysis using hematoxylin and eosin staining by a board-certified dermatopathologist masked to the burn therapy at 7, 9, 11, and 13 days after injury. The primary outcome was time to complete reepithelialization of the burns. Secondary outcomes were the percentage of burns that were reepithelialized at days 7, 11, and 13 and the mean percentage reepithelialization on microscopic analysis. A sample of 20 burns in each group had 80% power to detect a 2-day difference in the time to complete reepithelialization (two-tailed, P < .05). Application of Debrase?, but not the control vehicle, resulted in dissolution of the necrotic upper dermis in all treated burns. The mean time to complete reepithelialization was faster for Debrase?-treated (7.4 ± 0.8 days) than control-treated (9.1 ± 2.1 days) burns: difference, 1.7 days (95% confidence interval, 0.5-2.9). The percentage of completely reepithelialized Debrase?- and control-treated burns were day 7, 65.0 vs 25.0% (P = .02); day 9, 80.0 vs 40.0% (P = .02); and day 11, 100.0 vs 92.0% (P = .45). Treatment of mid-dermal porcine burns with a single topical application of Debrase? results in earlier wound reepithelialization.     

Characterization of the novel P-selectin inhibitor PSI-697 [2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h] quinoline-4-carboxylic acid] in vitro and in rodent models of vascular inflammation and thrombosis

P-selectin plays a significant and well documented role in vascular disease by mediating leukocyte and platelet rolling and adhesion. This study characterizes the in vitro activity, pharmacokinetic properties, and the anti-inflammatory and antithrombotic efficacy of the orally active P-selectin small-molecule antagonist PSI-697 [2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h] quinoline-4-carboxylic acid; molecular mass, 367.83]. Biacore and cell-based assays were used to demonstrate the ability of PSI-697 to dose dependently inhibit the binding of human P-selectin to human P-selectin glycoprotein ligand-1, inhibiting 50% of binding at 50 to 125 microM. The pharmacokinetics of PSI-697 in rats were characterized by low clearance, short half-life, low volume of distribution, and moderate apparent oral bioavailability. A surgical inflammation model, using exteriorized rat cremaster venules, demonstrated that PSI-697 (50 mg/kg p.o.) significantly reduced the number of rolling leukocytes by 39% (P < 0.05) versus vehicle control. In a rat venous thrombosis model, PSI-697 (100 mg/kg p.o.) reduced thrombus weight by 18% (P < 0.05) relative to vehicle, without prolonging bleeding time. Finally, in a rat carotid injury model, PSI-697 (30 or 15 mg/kg p.o.) administered 1 h before arterial injury and once daily thereafter for 13 days resulted in dose-dependent decreases in intima/media ratios of 40.2% (P = 0.025) and 25.7% (P = 0.002) compared with vehicle controls. These data demonstrate the activity of PSI-697 in vitro and after oral administration in animal models of both arterial and venous injury and support the clinical evaluation of this novel antagonist of P-selectin in atherothrombotic and venous thrombotic indications.     

严重烧伤早期大鼠心肌肌球蛋白ATP酶活性变化及其机制的实验研究

目的：探讨心肌肌球蛋白ＡＴＰ酶活性在严重烧伤后的变化特点及其机制。方法：用热水浴法造成３０％体表面积Ⅲ度烧伤大鼠模型并测定心肌营养性血流（ＮＢＦ）、血清心肌肌球蛋白轻链Ⅰ（ＣＭＬＣ１）和心肌肌球蛋白ＡＴＰ酶活性。结果：严重烧伤２４小时内，随着ＮＢＦ的减少，ＣＭＬＣ１含量大幅度升高，心肌肌球蛋白ＡＴＰ酶活性显著下降。结论：提示心肌血液灌流不足，心肌缺血缺氧导致心肌肌球蛋白崩解是烧伤早期心肌肌球蛋白ＡＴＰ酶活性下降的重要原因之一；心肌肌球蛋白ＡＴＰ酶活性下降在烧伤早期心肌收缩性减弱的发病学中具有重要作用。     

CAN PROPHYLACTIC ORAL ERYTHROMYCIN REDUCE TIME TO FULL ENTERAL FEEDS IN PRETERM NEONATES?

Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur.     

Hydrofluoric acid burns: a 15-year experience

Hydrofluoric acid (HF) is a strong inorganic acid commonly used in many domestic and industrial settings. It is one of the most common chemical burns encountered in a burn center and frequently engenders controversy in its management. We report our 15 year experience with management of HF burns. We reviewed our experience from 1990 to 2005 for patients admitted with HF burns. Primary treatment was with calcium gluconate gel. Arterial infusion of calcium and fingernail removal were reserved for unrelenting symptoms. There were 7944 acute burn admissions to our center during this study period, 204 of which were chemical burns. HF burns comprised 17% of these chemical burn admissions (35 patients). All were men, with a mean burn size of 2.1 +/- 1.5% (range, 1-6%) and hospital stay of 1.6 +/- 0.7 days (range, 0-3 days). The most common seasonal time of injury was in the summer. Twelve patients (34%) were admitted to the intensive care unit for a total of 14 intensive care unit days, primarily for arterial infusions. Ventilator support was not required in any patient. No electrolyte abnormalities occurred. All burns were either partial thickness or small full thickness with no operative intervention required and no deaths. The upper extremity was most commonly involved (29 patients, 83%). The most common cause was air conditioner cleaner (8 patients, 23%). HF is a common cause of chemical burns. Although hospital admission is usually required for vigorous treatment and pain control, burn size is usually small and does not cause electrolyte abnormalities, significant morbidity, or death.     

Apolipoprotein A-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complex (ETC-216) protects the in vivo rabbit heart from regional ischemia-reperfusion injury

Ex vivo studies demonstrated that a synthetic high-density lipoprotein (HDL) comprised of a complex of recombinant apolipoprotein A-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine protects the isolated rabbit heart from reperfusion injury. Therefore, we sought to determine whether a pharmaceutical preparation of this complex, ETC-216, was cardioprotective in an in vivo model of left anterior descending artery (LAD) occlusion and reperfusion. Initially, ETC-216 (100 mg/kg) was tested in acute (one-treatment) and chronic (two-treatment) i.v. administrations. ETC-216-treated rabbits developed smaller infarcts expressed as percentage of area at risk (p <0.01) compared with vehicle treatments. No differences were noted between chronic and acute administration. Therefore, ETC-216 (10, 3, or 1 mg/kg) or equivalent vehicle volumes were acutely infused. Compared with vehicle, ETC-216 reduced infarct size as a percentage of the area at risk at 10 (p <0.0005) and 3 mg/kg (p <0.05). No significant differences occurred at 1 mg/kg. To determine whether ETC-216 could protect the heart after initiation of ischemia, the synthetic HDL (10 mg/kg) was infused intravenously beginning 5 min before the end of 30 min of LAD occlusion. Infarct size as percentage of the area at risk was 31.6 +/- 3.0 (ETC-216) versus 49.5 +/- 2.5 (vehicle) (p <0.001), and as percentage of left ventricle was 19.7 +/- 1.6 (ETC-216) versus 34.1 +/- 2.3 (vehicle) (p <0.0005). Electron microscopy demonstrated that ETC-216 prevented irreversible cardiac damage as assessed by mitochondrial granulation and sarcomere contraction band formation. These findings suggest ETC-216 reduces reperfusion injury and may have utility for coronary artery revascularization procedures.     

The Effects of Epidermal Debridement of Partial-thickness Burns on Infection and Reepithelialization in Swine

OBJECTIVE: Early postburn debridement of burn blisters is controversial. This study was conducted to compare rates of infection and reepithelialization in debrided vs nondebrided second-degree burns in swine. METHODS: This was a prospective, blinded, controlled, experimental trial using isoflurane-anesthetized swine. Standardized partial-thickness burns were inflicted by applying an aluminum bar preheated to 80 degrees C to the backs and flanks of two young pigs for 20 seconds. In half of the burns the necrotic epidermis was manually debrided. All burns were randomly treated with octylcyanoacrylate spray (OCA) or dry gauze (C). Full-thickness biopsies were taken at 7, 10, and 14 days for blinded histopathologic evaluation. The primary outcomes were the proportions of infected burns at days 7 and 10 and the proportion of completely reepithelialized burns at day 14. Burns were considered infected in the presence of intradermal neutrophils containing bacteria (intraobserver agreement, K = 1.00). A secondary outcome was the proportion of burns with the presence of scar tissue (abnormal collagen under polarized light; intraobserver correlation, K = 0.93). Chi-square tests were used for group comparisons. This study had 90% power to detect a 40-percentage-point difference in infection rates (alpha = 0.05). RESULTS: A total of 126 biopsies from 42 burns were available for review. Infection rates were higher in the debrided burns both at day 7 (55% vs 4.5%, p < 0.001) and at day 10 (65% vs 9%, p < 0.001) after injury. The proportion of nondebrided burns that were completely reepithelialized was higher at days 10 (68% vs 0%, p < 0.001) and 14 (100% vs 65%, p = 0.003). The presence of scar tissue was more common in debrided burns (75% vs 4.5%, p < 0.001). Burns treated with OCA had fewer infections than controls (4% vs 55%, p < 0.001). Fewer OCA-treated debrided burns were reepithelialized at 14 days than those that were not debrided (30% vs 100%, p = 0.001). CONCLUSIONS: Under the current study conditions, early postburn epidermal debridement of second-degree burns resulted in more infections and slower reepithelialization rates in swine. The effects of early postburn epidermal debridement in humans should be explored.     

烫伤大鼠组织肿瘤坏死因子α受体基因表达的变化

目的：观察烫伤后机体主要脏器肿瘤坏死因子α（ＴＮＦα）及其受体（ＴＮＦＲ）ｍＲＮＡ表达的变化规律及二者的平衡关系。方法：采用大鼠３５％Ⅲ度烫伤模型,分别于伤前、伤后１２、２４、４８、７２小时活杀动物。留取组织和血标本分别检测组织ＴＮＦα、ＴＮＦＲｍＲＮＡ表达及器官功能指标。结果：烫伤后组织ＴＮＦα基因表达明显增强,而ＴＮＦＲｍＲＮＡ表达则呈持续降低趋势。同时,烫伤后各组织ＴＮＦα／ＴＮＦＲｍＲＮＡ比值显著增加,其中以肺组织升高最为显著。相关分析表明,肝组织ＴＮＦＲｍＲＮＡ表达、ＴＮＦα／ＴＮＦＲｍＲＮＡ比值与血清谷草转氨酶（ＧＯＴ）呈显著相关（Ｐ＜０．０５和Ｐ＜０．０１）,肾组织ＴＮＦＲｍＲＮＡ表达与血清肌酐（ＳＣｒ）呈显著负相关（Ｐ＜０．０１）。结论：烫伤可明显上调机体主要脏器ＴＮＦαｍＲＮＡ的表达,而ＴＮＦＲ基因表达则呈下调反应,提示ＴＮＦα和ＴＮＦＲ比例严重失调可能参与了烧伤后多器官功能损害的病理生理过程。     

Thermoregulation in burn patients during exercise

The purpose of this study was to assess the ability of patients with burns on 30 to 40% and 60% or greater of their BSA to thermoregulate their core temperature during exercise in the heat. Two groups (n = 3 in each) of subjects with healed third-degree burns (34.0 +/- 1.4% and 77.7 +/- 12.4%, respectively) and a group of unburned subjects (n = 2) exercised for 1 hour on a cycle ergometer at 75 Watts in an environmental chamber set at 35 degrees C and 60% relative humidity. Subjects were monitored for rectal and skin temperatures, heart rate, whole body sweat rate, skin blood flow, and active sweat gland density (number per cm ) in unburned, burned, and harvested skin. The results demonstrated that patients with burns on 60% or greater BSA did not show an intolerance to moderate exercise in the heat, as evidenced by only a moderate rise in rectal temperature and heart rate. Furthermore, the responses were similar to those of the unburned subjects.     

Feasibility of biolistic gene therapy in burns

Skin is an especially attractive target for genetic manipulation because it is readily accessible and easily monitored for both the presence and the expression of inserted genes. This study was designed to assess the feasibility of particle mediated gene transfer to burned skin and to compare the transfection efficiency, anatomic distribution, and duration of transgene expression achievable in normal versus burned skin. Two days following scald injury of varying depths in 60 degrees C water (10 s: superficial partial; 20 s: deep partial; 40 s: full thickness) reporter gene (beta-galactosidase) constructs were delivered using a gene gun at various helium pressures (200-600 psi) to normal and burned skin. A time course study was performed to examine the kinetics of transgene expression. Animals received a superficial partial thickness burn and were sacrificed 12 h, 1, 3, 5, 7, 14, or 21 days after gene transfer. India Ink injection and immunohistochemistry were used to assess the depth of the scald injury. Transfection efficiency was measured in skin homogenates 24 h after gene transfer by morphometric and chemoluminescent assays. We found that the extent of tissue damage was directly related to the duration of heat source exposure. Reporter gene activity was significantly higher in superficial partial thickness burns compared to normal controls and gradually declined with increasing tissue injury. No activity was seen in the full thickness burn group. Beta-galactosidase activity reached a maximum level 12 h after gene transfer in both normal and superficial partial thickness burned skin with no levels seen after 5 days post-transfection. These findings indicate that particle-mediated gene transfer in thermally injured skin is feasible and may provide a means of introducing biologic agents into injured tissue capable of enhancing bacterial clearance and improving wound healing.     

Results of an internet survey on the treatment of partial thickness burns, full thickness burns, and donor sites.

The objective of this study was to analyze which materials and methods are used for the management of partial and full thickness burns, as well as donor sites. An Internet survey was used to poll directors of burn centers around the world on their preferences for local treatment of different types of burns and donor sites. Results were tabulated and expressed as a percentage of the total number of answers for a given indication. Although many new wound care materials have been launched in the last decade, few of these actually are used widely. The most commonly used materials for partial thickness burns and donor sites are still silver sulphadiazine 1% cream, other antimicrobial ointments and creams and impregnated gauze type dressings. Of the newly available treatment modalities, only two silver dressings were chosen frequently as a primary option for the management of partial thickness burns and donor sites. For full thickness burns, the primary choice is excision and grafting. The diversity of dressings and techniques indicated as preferred in this survey, including many that are known to have side effects, indicates that there is no consensus on topical treatment of partial thickness burns and donor sites. Many respondents prefer "tried and true" materials over newer dressings, particularly if the latter have not been tested in a clinical trial.     

The domestic iron. A danger to young children

OBJECTIVES: To study the epidemiology of thermal injury caused by the domestic iron in children 5 years old or less. METHODS: Retrospective review of case notes held in the accident and emergency (A&E) department of a large teaching hospital over a 36 month period. Data regarding demographics, site and extent of injury, mechanism of injury and outcome were retrieved. RESULTS: 62 thermal injuries were identified in 59 patients. Of these, 60 were contact burns and two were scalds. The male to female ratio was 2:1. The mean age was 24 months. Fifty five per cent were aged between 1 and 2 years old. The hand was the commonest site of injury (63%) and, of these, two thirds were on the palm. Interestingly 10% occurred on the face. Iron contact burns accounted for 23.5% of all contact burns in this age group over this period. The majority of contact burns were partial thickness and most were less than 1% body surface area. Inadequate supervision is a recurring theme in many of these cases. A suspicion of non-accidental injury was raised in 10 cases and confirmed in nine of these. CONCLUSIONs: Iron burns are common in young children, particularly boys aged between 1 and 2 years old. Most can be treated in the A&E clinic. The potential for serious injury does exist. Non-accidental injury always needs to be considered. Efforts at prevention and increasing public awareness are needed.     

Increased mortality with intravenous supplemental feeding in severely burned patients

Patients with large cutaneous burns are characterized by an elevated metabolic rate and lose up to 25% of their body weight within 3 weeks. A previous study suggested that intravenous supplementation to attain nutritional requirements was of no benefit in patients with cutaneous burns covering greater than 50% of their total body surface area. In this study 39 patients with burns greater than 50% of their total body surface area were randomly assigned to receive intravenous supplementation of enteral calories (n = 16) or enteral calories alone (n = 23). Intravenous supplementation decreased the amount of enteral calories that patients with burns could tolerate. The mortality rate was significantly higher (p less than 0.05) in the intravenously supplemented group at 63% as compared with 26% in the group receiving enteral calories alone. Both groups showed significant decrease in natural killer cell activity when compared with controls at both 0 to 7 and 7 to 14 days after injury. T cell helper/suppressor ratios were depressed in both groups when compared with controls; however, the intravenously supplemented group was significantly depressed at 7 to 14 days after burn. Both groups demonstrated hepatomegaly, moderate fatty infiltration, and cholestasis. It is suggested that intravenous supplementation should be carefully evaluated and used only in patients with total enteral failure.     

Burns caused by carburetors

During a 10-year period 4645 patients were admitted to the Joseph M. Still Burn Center with acute burns. Of these, 83 (1.79%) were caused by carburetor-related accidents. There were 79 males and 4 females. Ages ranged from 10 to 72 years. Burn size ranged from 1 to 97.5% (mean, 12.3%). There was one death in the group. Eighteen patients required only topical care; 65 patients required a total of 108 operations for debridement and grafting. Length of stay ranged from 1 to 63 days (mean, 11 days). The mechanism of injury was usually the same; in 81 cases the accident occurred while someone was pouring gasoline into a carburetor. In 63 cases the vehicle was an automobile or pickup truck. Explosions resulted in 12 instances; in 65 instances fires were started. These injuries are serious, expensive, fairly common, and may be life threatening. Proper handling of gasoline is stressed. Newer vehicles have fuel injector systems, which may gradually eliminate the problem over time, because pouring gasoline is not required.     

Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients

BACKGROUND: Recent data from military and civilian centers suggest that mortality is decreased in massive transfusion patients by increasing the transfusion ratio of plasma and platelet (PLT) products, and fibrinogen in relationship to red blood cell (RBC) products during damage control resuscitation and surgery. This study investigates the relationship of plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios to mortality in massively transfused patients at a civilian Level 1 trauma center. STUDY DESIGN AND METHODS: Demographic, laboratory, transfusion, and outcome data were collected prospectively from February 1, 2007, to January 31, 2009, and retrospectively from February 1, 2005, to January 31, 2007, on all injured patients who underwent massive transfusion (defined as ≥10 RBC products within 24 hr). Mortality was analyzed in relation to the plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios using both univariate and multivariate analyses. RESULTS: A total of 214 patients received massive transfusion secondary to traumatic injury. High versus low transfusion ratios were associated with improved 30‐day survival: plasma:RBC 59% versus 44%, p = 0.03; PLT:RBC 63% versus 33%, p < 0.01; and cryoprecipitate:RBC 66% versus 41%, p < 0.01. By multivariable stepwise logistic regression analysis, increased plasma:RBC (p = 0.02) and PLT:RBC (p = 0.02), and decreased age (p = 0.02), ISS (p < 0.01) and total RBCs (p = 0.03) were statistically associated with improved 30‐day survival. CONCLUSIONS: In the civilian setting, plasma, PLT, and cryoprecipitate products significantly increased 30‐day survival in trauma patients. Future prospective randomized clinical trials are required to determine the optimal transfusion ratios.     

How well does the Parkland formula estimate actual fluid resuscitation volumes?

We had anecdotally observed that fluid resuscitation volumes often exceed those estimated by the Parkland Formula in adults with isolated cutaneous burns. The purpose of this study was to compare estimated and actual fluid resuscitation volumes using the Parkland Formula. We performed a retrospective study of fluid resuscitation in patients with burns > or = 15% TBSA. Patients with inhalation injury, high voltage electrical injury, delayed resuscitation, or associated trauma were excluded. We studied 31 patients (mean age 51 +/- 20 years, mean TBSA burn 27 +/- 10%). The 24 hour resuscitation volume of 13 354 +/- 7386 ml (6.7 +/- 2.8 ml/kg/%TBSA) was significantly greater than predicted (P = 0.001) and exceeded estimated volume in 84% of the patients. The mean urine output in the first 24 hrs was 1.2 +/- 0.6 ml/kg/hr. After the first 8 hours of resuscitation, the infusion rate decreased by 34% in 16 patients (DCR group), while in 15 patients the rate increased by 47% (INCR group). Both the DCR and INCR groups received significantly more fluid than predicted, (5.6 +/- 2.1 ml/kg/%TBSA and 7.7 +/- 3.1 ml/kg/%TBSA respectively). The INCR patients had significantly larger full thickness burns (14 +/- 11% vs 3 +/- 6%, P < 0.001). Our findings reveal that despite its effectiveness, the Parkland Formula underestimated the volume requirements in most adults with isolated cutaneous burns, and especially in those with large full thickness burns.     

Inhibition of leukocyte-mediated tissue destruction by synthetic fibronectin peptide (Trp-9-Tyr)

Burns are surrounded by an inflammatory zone of stasis that can progress to ischemia and extension of burn size. Synthetic fibronectin peptides have reduced tissue destruction in several models of inflammation. In this study, we postulate that administration of the peptide Trp-9-Tyr will alter the progression of tissue destruction following thermal injury. Baseline cutaneous blood flow was measured on New Zealand White rabbits with a laser doppler blood-flow meter. While the rabbits were under general anesthesia, 6 full-thickness burns were produced on the rabbits' backs. Blood flow in the zones of stasis was followed daily, and the number of zones that progressed to necrosis was determined at 72 hours. There were 3 experimental groups. Ten control animals received saline. Ten were treated with Trp-9-Tyr for 24 hours postburn. Ten received Trp-9-Tyr for 48 hours. Animals treated with Trp-9-Tyr had higher blood flow and less necrosis in the zones of stasis than did control animals, which was evident at 24 hours but more significant at 48 hours.     

Development and Validation of the Excess Mortality Ratio–adjusted Injury Severity Score Using the International Classification of Diseases 10th Edition

Objectives: This study aimed to develop and validate a new method for measuring injury severity, the excess mortality ratio–adjusted Injury Severity Score (EMR‐ISS), using the International Classification of Diseases 10th Edition (ICD‐10). Methods: An injury severity grade similar to the Abbreviated Injury Scale (AIS) was converted from the ICD‐10 codes on the basis of quintiles of the EMR for each ICD‐10 code. Like the New Injury Severity Score (NISS), the EMR‐ISS was calculated from three maximum severity grades using data from the Korean National Injury Database. The EMR‐ISS was then validated using the Hosmer‐Lemeshow goodness‐of‐fit chi‐square (HL chi‐square, with lower values preferable), the area under the receiver operating characteristic curve (AUC‐ROC), and the Pearson correlation coefficient to compare it with the International Classification of Diseases 9th Edition–based Injury Severity Score (ICISS). Nationwide hospital discharge abstract data (DAD) from stratified‐sample general hospitals (n = 150) in 2004 were used for an external validation. Results: The total number of study subjects was 29,282,531, with five subgroups of particular interest identified for further study: traumatic brain injury (TBI, n = 3,768,670), traumatic chest injury (TCI, n = 1,169,828), poisoning (n = 251,565), burns (n = 869,020), and DAD (n = 26,374). The HL chi‐square was lower for EMR‐ISS than for ICISS in all groups: 42,410.8 versus 55,721.9 in total injury, 7,139.6 versus 20,653.9 in TBI, 6,603.3 versus 4,531.8 in TCI, 2,741.2 versus 9,112.0 in poisoning, 764.4 versus 4,532.1 in burns, and 28.1 versus 49.4 in DAD. The AUC‐ROC for death was greater for EMR‐ISS than for ICISS: 0.920 versus 0.728 in total injury, 0.907 versus 0.898 in TBI, 0.675 versus 0.799 in TCI, 0.857 versus 0.900 in poisoning, 0.735 versus 0.682 in burns, and 0.850 versus 0.876 in DAD. The Pearson correlation coefficient between the two scores was ?0.68 in total injury, ?0.76 in TBI, ?0.86 in TCI, ?0.69 in poisoning, ?0.58 in burns, and ?0.75 in DAD. Conclusions: The EMR‐ISS showed better calibration and discrimination power for prediction of death than the ICISS in most injury groups. The EMR‐ISS appears to be a feasible tool for passive injury surveillance of large data sets, such as insurance data sets or community injury registries containing diagnosis codes. Additional further studies for external validation on prospectively collected data sets should be considered.