Postburn Day Research Articles

Natriuretic peptide proANP (1–98), a biomarker of ALI/ARDS in burns

Plasma atrial natriuretic peptide levels (proANP (1-98)), a parameter of myocardial dysfunction, have been reported to be increased in critically ill patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The aim of the study was to examine if proANP is a biomarker of ALI/ARDS as assessed by the Sequential Organ Failure Assessment score (SOFA Lung ≥2) in burn patients, and how it compares to the corresponding values for age, total body surface area percent (TBSA%) and inhalation injury for mortality prediction. A group of 22 burn patients with a mean TBSA of 30% (10-75%) and a mean age of 52 years (25-84 years) was investigated during 2010. Organ dysfunction/failure was classified according to the SOFA score. The criteria for ALI/ARDS were based on SOFA Lung ≥2. ProANP (1-98) concentrations (nmoll(-1)) were measured by commercially available enzyme linked immunosorbent assay (ELISA) immunoassays (Biomedica Austria) on post-burn days 2 and 7. ProANP levels on day 7 post-burn positively correlated with a SOFA score day 7 post-burn, c=0.91. The receiver operating curve (ROC) analysis proved a sensitivity of 75% and a specificity of 75% for ALI/ARDS at cut-off values >3.35 nmoll(-1). The ROC value of proANP for ALI/ARDS (SOFA Lung ≥2) was significantly larger than that of age, TBSA% and inhalation injury: 0.90, 0.71, 0.74, and 0.69 (p<0.001). ProANP levels, as a biomarker of ALI/ARDS, in critically burn patients correlated with SOFA scoring. The inhalation injury did not lead to increase in proANP values.

Cimetidine enhances delayed-type hypersensitivity responses and serum interleukin (IL)-2, -10, -12, and IL-17 levels after burn injury in an animal model

The immunosuppression that occurs after burn injury causes an increase in susceptibility to infection. The aim was to investigate time-related alterations in various cytokines following thermal injury and to modulate cytokines by use of an immunomodulant, cimetidine. Male Balb/c mice were anesthetized and given a 10% total body surface area full-thickness burn by submerging in 90°C water for 9 s. Time-dependent changes in delayed type hypersensitivity (DTH) and serum levels of the cytokines IL-2, IL-10, IL-12, IL-17 and TGFβ were then assessed at various post-burn day (PBD) timepoints. Effects of 10 mg cimetidine/kg on DTH responses and cytokine levels were evaluated up to PBD 14. In comparison to healthy non-burned control mice, levels of IL-2 and IL-17 significantly decreased at PBD 3, 5, 10, and 14, those of IL-10 at PBD 1, 3, 5, and 10, and those of IL-12 at PBD 1, 3, 5, 10, and 14. Administration of cimetidine significantly augmented the levels of IL-2 (at PBD 3, 5, and 10), IL-10 (at PBD 1 and 5), IL-12 (at PBD 3, 5, 10, and 14), and IL-17 (at PBD 3 and 14) as compared to those in burned counterparts who did not receive drug. In comparison to healthy mice, biphasic alterations were observed regarding TGFβ levels; values were significant decreased and increased at PBD 3 and PBD 14, respectively. Cimetidine significantly diminished the elevated TGFβ levels at PBD 14. Cimetidine also significantly augmented DTH responses at PBD 5, 10, and 14 as compared to responses in non-drug-treated burned hosts. Taken together, the results here showed significant time-dependent changes in serum cytokines levels after burn injury and that cimetidine was able to significantly augment IL-2, IL-10, IL-12, and IL-17 levels as well as DTH responses that are normally suppressed following thermal trauma.

Locally Produced Microbial Cellulose Dressing from Acetobacter xylinum Compared with Silver Sulfadiazine Cream for Patients with Acute Superficial Partial Thickness Burn Wounds: A Randomized Controlled Trial

Objective: To compare the efficacy and safety of microbial cellulose (MCD) dressing from Acetobacter xylinum in promoting healing of superficial partial thickness burn wounds to standard dressing using silver sulfadiazine (SSD) cream and gauze in terms of the following: time to healing, pain score, scarring and infection rate. Population: Subjects included patients seen at the ATR Burn Center UP-PGH from February 2008 to December 2010. Patients were 18- 50 years of age with&lt;40% TBSA, acutely injured (≤ 48 hours) and with no uncontrolled medical condition. Pregnant patients were excluded. Methods: Each subject served as his own control, wherein burn wounds were randomized into 2 types of wound dressing. Wounds were assessed by a lone plastic surgeon blinded to all treatments. Results: Forty-five patients who fulfilled the inclusion criteria were seen and treated at the ATR Burn Center of the UP-PGH. Wounds dressed with MCD healed more rapidly compared to those dressed with SSD. The mean healing days were 8.51 and 12.07 for MC and SSD (P&lt;0.05). Only 29 subjects were able to return on the 30th post burn day for assessment of scarring. Conclusion: Locally produced MCD is more efficacious compared to SSD in the treatment of SPT burns in terms faster healing and lower VAS scores. Key words: superficial partial thickness burn, Acetobacter xylinum

The systemic effect of 830-nm LED phototherapy on the wound healing of burn injuries: A controlled study in mouse and rat models

Background: The present controlled study assessed the systemic effect of 830-nm LED phototherapy in rodent models. Materials and methods: Two HR-1 hairless mice and 3 HWY/Slc hairless rats were divided into two groups: the treatment group (Tx Group, one mouse, two rats) and the control group (Con Group, one mouse, one rat). All animals received an identical 12 mm × 12 mm control burn over three sites on the dorsum with a fractional ablative CO2 laser. Wounds were protected with a film-type dressing. The abdomen of the Tx Group subjects was irradiated with an 830-nm LED array immediately post CO2 treatment and then at 1, 5 and 6 days post laser irradiation. Wound healing was assessed macroscopically from the clinical photography. Results: At the 2-day post-laser assessment, the healing process in the wounds in the Tx Group was already apparent compared with the Con Group. At the final evaluation (post-burn day 7), no site on the Con Group (six wounds) showed 100% healing, recovery was over 70% in four and lower than 50% in two sites. Of the nine Tx Group sites, 100% recovery was seen in three sites, over 70% in five sites and one wound was exacerbated through trauma. Conclusions: LED phototherapy on the abdomen produced faster wound healing of the uniform burn wounds than in animals with the same burn wounds that did not receive LED phototherapy, strongly suggesting the systemic effect of phototherapy.

Management of ear burns

Ear is a very prominent part of the face after nose and eyes especially in Indian subcontinent where in both the males and females it adorns a variety of ornaments to beautify the face. However, because of limited functional importance of external ear the burns of the ear are often neglected. More often, isolated burns of the ear are very rare. They are usually involved with facial burns and therefore inhalational injuries. Overall management of burns to improve survival takes precedence over the management of just the burned ear. Therefore, neglected ear burns can lead to cosmetic deformity which can vary from minor to very severe. Giving due importance to this small structure can prevent a lot of morbidity during the acute phase and deformities later on as a sequel of burns. Correction of those deformities and giving a normal shape to the ear can be a very daunting task because of the intricacies involved in framing the cartilage and inadequate soft tissue availability in the surrounding area. This article emphasizes on the steps which can be taken from the first postburn day to avoid complications like chondritis, chondral abscess, and various other deformities because in a patient surviving burn injury, the quality of his or her life will be determined by the degree of these deformities.

Novel Mitochondria-Targeted Antioxidant Peptide Ameliorates Burn-Induced Apoptosis and Endoplasmic Reticulum Stress in the Skeletal Muscle of Mice

This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight), and the rectus abdominis muscles collected on postburn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses. Treatment with SS-31 peptide prevented burn-induced increases in the caspase 3 activity (P < 0.05) and apoptosis (P < 0.01) on postburn day 7. The SS-31 peptide treatment also prevented the increase in the expression levels of phosphatase and tensin homolog on postburn days 3 and 7. Burn injury-induced increases in the levels of two endoplasmic reticulum stress markers, binding immunoglobulin protein and protein disulfide isomerase, were significantly decreased by the SS-31 peptide treatments on postburn day 7 and on day 3 for binding immunoglobulin protein as well (P < 0.05). The effects of SS-31 appear to be, in part, due to its ability to reduce oxidative stress in burned mice, evidenced by reduced expression of oxidized proteins that were clearly evident on postburn day 7. Our results demonstrate a possible therapeutic potential of SS-31 peptide to ameliorate the adverse effects of burn injury in skeletal muscle.

Burn Injury Dampens Erythroid Cell Production Through Reprioritizing Bone Marrow Hematopoietic Response

Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury. After anesthesia, B(6)D(2)F(1) mice received a 15% total body surface area dorsal scald burn. The sham group did not receive scald burn. Femoral bone marrow was harvested on 2, 5, 7, 14, and 21 postburn days (PBD). Total bone marrow cells were labeled with specific antibodies to erythroid (CD71/Ter119), myeloid (CD11b), and lymphoid (CD19) lineages and analyzed by flow cytometry. To test whether erythropoietin (EPO) could increase red blood cell production, EPO was administered to sham and burn animals and their reticulocyte response was measured on PBD 2 and PBD 7. Burn injury reduced the erythroid cells of the bone marrow from 35% in sham to 17% by PBD 5 and remained at similar level until PBD 21. Myeloid cells, however, increased from 42% in sham to 60% on PBD 5 and 77% on PBD 21. Burn injury reduced reticulocyte counts on PBD 2 and PBD 7 indicating that the erythroid compartment is severely depleted. This depleted compartment, however, responded to EPO but was not sufficient to change red cell production. Burn injury skews the bone marrow hematopoietic commitment away from erythroid and toward myeloid cells. Shrinkage of the erythroid compartment contributes to resistance to EPO and the anemia of critical illness.

Reduction of Plasma Gelsolin Levels Correlates with Development of Multiple Organ Dysfunction Syndrome and Fatal Outcome in Burn Patients

BackgroundDepletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in critically ill surgical patients. We hypothesized that the extent of pGSN reduction might correlate with different outcome of burn patients. The study was performed to evaluate the prognostic implications of pGSN levels on the development of multiple organ dysfunction syndrome (MODS) and fatal outcome in a group of severely burn patients.Methods and Findings95 patients were included, and they were divided into three groups with different burn area: group I (n = 33), group II (n = 32) and group III (n = 30). According to whether there was development of MODS or not, patients were divided into MODS group (n = 28) and none-MODS group (n = 67); then the patients with MODS were further divided into non-survivor group (n = 17) and survivor group (n = 11). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The levels of pGSN were determined and T cells were procured from the blood. The contents of cytokines (IL-2, IL-4 and IFN-γ) released by T cells were also measured. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The results showed that pGSN concentrations, as well as the levels of IL-2 and IFN-γ, decreased markedly on PBD 1–21, whereas, the levels of IL-4 increased markedly in all burn groups as compared with normal controls (P<0.05 or P<0.01), and there were obviously differences between group I and group III (P<0.05 or P<0.01). The similar results were found in MODS patients and the non-survivor group as compared with those without MODS and the survival group on days 3–21 postburn (P<0.05 or P<0.01). Moreover, as the pGSN levels decreased, the incidence of septic complication as well as MODS remarkably increased.ConclusionspGSN levels appear to be an early prognostic marker in patients suffering from major burns.

Early Glycemic Control in Critically Ill Patients With Burn Injury

Glucose management in patients with burn injury is often difficult because of their hypermetabolic state with associated hyperglycemia, hyperinsulinemia, and insulin resistance. Recent studies suggest that time to glycemic control is associated with improved outcomes. The authors sought to determine the influence of early glycemic control on the outcomes of critically ill patients with burn injury. A retrospective analysis was performed at the Ohio State University Medical Center. Patients hospitalized with burn injury were enrolled if they were admitted to the intensive care unit between March 1, 2006, and February 28, 2009. Early glycemic control was defined as the achievement of a mean daily blood glucose of ≤150 mg/dl for at least two consecutive days by postburn day 3. Forty-six patients made up the study cohort with 26 achieving early glycemic control and 20 who did not. The two groups were similar at baseline with regard to age, pre-existing diabetes, APACHE II score and burn size and depth. There were no differences in number of surgical interventions, infectious complications, or length of stay between patients who achieved or failed early glycemic control. Failure of early glycemic control was, however, associated with significantly higher mortality both by univariate (35.0 vs 7.7%, P = .03) and multivariate analyses (hazard ratio 6.754 [1.16-39.24], P = .03) adjusting for age, TBSA, and inhalation injury. Failure to achieve early glycemic control in patients with burn injury is associated with an increased risk of mortality. However, further prospective controlled trials are needed to establish causality of this association.

Changing pattern of fungal infection in burn patients

Invasive fungal burn wound infection is an important emerging cause of late onset morbidity and high mortality in patients with major burns. Following a pilot study done in our unit in 1 year, i.e. January 2008–March 2009 in 71 patients where 28% (20 patients) of the burn wound biopsies from suspected cases showed fungal wound invasion (FWI), a detailed study was planned in order to study the epidemiology of fungal infection in burns in our unit wherein routine wound biopsies in 100 patients were sent on 7th, 14th and 21st postburn day over a one year period (July 2009–June 2010). 12 patients (12%) were diagnosed with FWI on culture. This was then followed by another study in a 9 month period (July 2010–March 2011) when wound samples for only 36 patients in whom there was clinical suspicion of fungal infection were sent. 16 of these patients were diagnosed with fungal wound invasion (FWI) thus establishing an incidence of 44% from suspected cases. These studies showing the increase in fungal infection in our unit have therefore made us wiser, increased our awareness and our accuracy in diagnosing this uncommon infection in extensive burns where patient is not only severely immunocompromised but also has many other risk factors making them more vulnerable to fungal invasion. Another glaring fact which emerged from these studies was the rising incidence of nonalbicans Candida infection compared to Candida albicans, especially C. tropicalis and C. krusei which are more severe in nature and associated with a higher mortality. This signifies that there is a shift of FWI in burns from commensal organism, i.e. C. albicans to pathogenic nosocomial organisms, i.e. C. nonalbicans.

Cerium nitrate treatment prevents progressive tissue necrosis in the zone of stasis following burn

Cerium nitrate (CN) was used as a topical antiseptic agent for the treatment of burn wounds and found to reduce the number of anticipated death in burn. This decreased burn related mortality cannot be explained by the control of wound infection alone. In the studies performed to elucidate the unexplained effects of CN treatment, it was shown that CN treatment reduced the alarm cytokine levels, decreased leukocyte activation, reduced macromolecular leakage and finally burn edema formation. We hypothesized that CN treatment prevents the conversion of the zone of stasis to progressive tissue necrosis by decreasing leukocyte activation and reducing macromolecular leakage and burn edema.This was investigated on a well-described burn comb model in the rats. Fifty-four rats were randomly divided into control and CN treatment groups. Each rat in CN treatment group received 0.04M CN bathing 30min after burn whereas rats in control group received 0.09% saline bathing. Viability of zone of stasis is assessed with 99mTc-sestamibi scintigraphy. Nine rats in each group were scintigraphically evaluated at the 3rd and 7th day after burn and remaining 9 rats had macroscopic and histological examination at the 21st day after burn to confirm the scintigraphic results.In CN treatment groups, the scintigraphic uptake ratios were higher both at post burn day 3rd and 7th when compared to that of control groups. This was statistically significant (p≤0.05). In the CN treatment group, the results of the average percentage of the re-epithelialization in the zone of stasis were higher than that of control groups. The difference between the groups was also statistically significant (p≤0.05).These results were accepted that CN treatment prevents progressive tissue necrosis in the zone of stasis. This study further elucidates the unexplained effects of CN treatment on burn.

Astragalus Polysaccharides Attenuate Postburn Sepsis via Inhibiting Negative Immunoregulation of CD4+CD25high T Cells

BackgroudAstragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. However, it is not yet clear whether APS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of APS on the immune function of peripheral blood Tregs in postburn sepsis.Methodology/Principal FindingsBalB/c mice were randomly divided into six groups as follows: sham burn group, burn control(burn without infection animals) group, burn plus P. aeruginosa group, burn plus P. aeruginosa with APS (50 mg/kg) treatment group, burn plus P. aeruginosa with APS (100 mg/kg) treatment group, and burn plus P. aeruginosa with APS (200 mg/kg) treatment group, and they were sacrificed on postburn day 1, 3, 5, and 7, respectively, with seven animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4+ T cells. Phenotypes were analyzed by flow cytometry, and cytokine levels were determined with ELISA. In the burn plus P. aeruginosa group, forkhead/winged helix transcription factor p3 (Foxp3) expression on CD4+CD25+Tregs were strongly enhanced in comparison to the sham group, and the capacity of CD4+CD25+Tregs to produce interleukin (IL)-10 was markedly increased. Administration of APS to inhibit CD4+CD25+Tregs could significantly decrease expression of Foxp3 on CD4+CD25+Tregs, and IL-10 production in burned mice with P. aeruginosa infection. At the same time, proliferative activity and expression of IL-2 and IL-2Rα on CD4+ T cells were restored. In contrast, anti-Toll-like receptor 4 (TLR4) antibody could block the effect of APS on Tregs immune function.ConclusionAPS might suppress CD4+CD25+Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1 with activation of CD4+ T cells in burned mice with P. aeruginosa infection.

Neuromuscular pharmacodynamics of mivacurium in adults with major burns

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Early Escharectomy and Concurrent Composite Skin Grafting over Human Acellular Dermal Matrix Scaffold for Covering Deep Facial Burns

Although escharectomy and full-thickness skin autografting have been widely used to treat deep facial burns, the clinical outcomes remain unacceptable. Composite razor-thin skin grafting over acellular dermal matrix scaffold has been used successfully in repairing burns of the trunk and limbs, but its use in covering deep facial burns has rarely been reported. In this study, the authors investigated the clinical outcomes of early escharectomy and concurrent composite razor-thin skin autografting and acellular dermal matrix scaffold for treating deep facial burns. Patients with deep facial burns (n = 16) involving 8 to 30 percent of the total body surface area received early escharectomy by postburn day 3 and concurrent, one-stage, large, razor-thin skin autografting on top of human acellular dermal matrix scaffold. Wound dressings were changed on postoperative days 7, 9, and 12 to examine the survival of skin autografts. Patients were followed up for 12 months to evaluate their facial profiles. The take rate of composite skin autografts was 97.3 percent at postoperative day 12. At the follow-up visit, the skin autografts appeared normal in color, with soft texture and good elasticity. The skin junctures showed little scarring. The patients exhibited a chubby facial appearance and abundant expression, except for one patient with microstomia and two patients with ectropion who required further plastic surgical interventions. Early escharectomy and concurrent composite razor-thin skin autografting on top of acellular dermal matrix scaffold constitute an effective and favorable option for covering deep facial burns, especially for patients with limited donor sites.

The Burn Wound Inflammatory Response Is Influenced by Midazolam

Burn patients requiring hospitalization are often treated for anxiety with benzodiazepines (BDZs). Benzodiazepines are reported to influence immune system function. Immune system alterations are a major cause of burn-induced mortality. We wanted to determine whether the BDZ, midazolam given daily at an anxiolytic dose, had any influence on the burn injury-induced inflammatory response in the blood and wound. Mice received a 15% total body surface area flame burn and received either midazolam 1 mg/kg i.p. or saline 0.1 ml daily. Blood and skin wounds were harvested 24 h after injection on post-burn day 2, 3, 7, or 8. Mice treated with midazolam had significantly lower serum IL-1β (p=0.002), TNF-α (p=0.002), IL-6 (p=0.016), IL-10 (p=0.009), and TGF-β (p=0.004) than saline-treated mice, with little impact on serum chemokine levels. In the wound, TNF-α and IL-10 were the only cytokines significantly influenced by the drug, being lower (p=0.018) and higher (p=0.006), respectively. The chemokines in the wound influenced significantly by midazolam were MIP-1α, MIP-1β, and MIP-2 while MCP-1 and KC were not. There were more inflammatory cells at the burn wound margin in midazolam-treated mice on post-burn day 3. Although serum nitrate/nitrite was significantly increased by midazolam (p=0.03), both eNOS and iNOS mRNA expression in the wound were similar to the saline group. We found that midazolam given daily after burn injury significantly influenced the inflammatory response. The clinical implications of these findings on wound healing and shock following burn injury, especially larger burns, deserve further investigation.

Surgical Burn Wound Infections and Their Clinical Implications

Typically, burn wound infections are classified by the organisms present in the wound within the first several days after injury or later by routine surveillance cultures. With universal acceptance of early excision and grafting, classification of burn wound colonization in unexcised burn wounds is less relevant, shifting clinical significance to open burn-related surgical wound infections (SWIs). To better characterize SWIs and their clinical relevance, the authors identified the pathogens responsible for SWIs, their impact on rates of regrafting, and the relationship between SWI and nosocomial infection (NI) pathogens. Epidemiologic and clinical data for 71 adult patients with ≥ 20% TBSA burn were collected. After excision and grafting, if a grafted site had clinical characteristics of infection, a wound culture swab was obtained and the organism identified. Surveillance cultures were not obtained. SWI pathogen, anatomic location, postburn day of occurrence, and need for regrafting were compiled. A positive culture obtained from an isolated anatomic location at any time point after excision and grafting of that location was considered a distinct infection. Pathogens responsible for NIs (urinary tract infections, pneumonia, bloodstream and catheter-related bloodstream infections, pseudomembranous colitis, and donor site infections) and their postburn day were identified. The profiles of SWI pathogens and NI pathogens were then compared. Of the 71 patients included, 2 withdrew, 6 had no excision or grafting performed, and 1 had incomplete data. Of the remaining 62 patients, 24 (39%) developed an SWI. In these 24 patients, 70 distinct infections were identified, of which 46% required regrafting. Candida species (24%), Pseudomonas aeruginosa (22%), Serratia marcescens (11%), and Staphylococcus aureus (11%) comprised the majority of pathogens. Development of an SWI with the need for regrafting increased overall length of stay, area of autograft, number of operative events, and was closely associated with the number of NIs. The %TBSA burn and depth of the burn were the main risk factors for SWI with need for regrafting. The SWI pathogen was identified as an NI pathogen 56% of the time, with no temporal correlation between shared SWI and NI pathogens. SWIs are commonly found in severely burned patients and are associated with regrafting. As a result, patients with SWIs are subjected to increased operative events, autograft placement, and increased length of hospitalization. In addition, the presence of an SWI may be a risk factor for development of NIs.

Comparison of silver-coated dressing (Acticoat ®), chlorhexidine acetate 0.5% (Bactigrass ®) and nystatin for topical antifungal effect in Candida albicans-contaminated, full-skin-thickness rat burn wounds

Background In this experimental animal study, the effects of three different topical antimicrobial dressings on Candida albicans contaminated full-thickness burn in rats were analyzed. Methods In total 32 adult Wistar rats (body weight 200–220 g) were used. Silver-coated dressing (Acticoat™ ®), chlorhexidine acetate 0.5% (Bactigrass ®) and Mycostatine (Nystatin ®) were compared to assess the antifungal effect of a once-daily application on experimental rat 15% full-skin thickness burn wound seeded 24 h earlier with a 10 8 CFU/mL standard strain of C. albicans ATCC 90028. All the animals were sacrificed at post burn day 7. The quantitative counts of seeded organism in burn eschar and subjacent muscle were determined, in addition to the cultures of left ventricle blood and lung biopsies. Results While there were significant differences between Acticoat™ ® group (4 ± 10 × 10 4) and control group (5 ± 6 × 10 6), and between Nystatin group (4 ± 4 × 10 4) and control group ( P = 0.01, P = 0.01), there were no significant differences between chlorhexidine acetate 0.5% group (2 ± 3 × 10 4) and control group ( P = 0.7 ) respectively. Acticoat™ ® and Nystatin were sufficient to prevent to C. albicans from invading to the muscle and from causing systemic infection. Conclusions The animal data suggest that nystatin is the most effective agents in the treatment of C. albicans-contaminated burn wounds, and Acticoat™ ® is a choice of treatment on fungal burn wound infection with antibacterial effect and the particular advantage of limiting the frequency of replacement of the dressing.

Simvastatin treatment improves survival in a murine model of burn sepsis: Role of interleukin 6

Infection is the most common and most serious complication of a major burn related to burn size. Recent studies have demonstrated that statin treatment can decrease mortality in murine or human sepsis. In the current study mice were anesthetized and subjected to a dorsal 30% TBSA scald burn. Simvastatin or placebo were administered by intraperitoneal injection once daily or every 12 h. On post burn day 7 cecal ligation and puncture with a 21-gauge needle (CLP) was performed under ketamine/xylazine anesthesia, the two different dosing schedules were continued and survival was monitored. In other groups of mice, interleukin-6 (IL-6) levels in blood were measured in mice at 7 days after injury. A simvastatin dependent improvement in survival was observed in the burn sepsis model. This protection was found to be dose and time dependent. In addition, statin treatment reduced the elevation in IL-6 levels of mice burned 7 days previously. However, IL-6 levels in burned mice with or without statin treatment were elevated by CLP to the same degree. The results of these studies suggest that statin treatment reduces mortality in mice with burns and CLP and that this effect may not be mediated via IL-6 levels.

A Ribonucleotide Reductase Inhibitor Reverses Burn-Induced Inflammatory Defects

Immature myeloid cells have been implicated as a source of postburn inflammation, and the appearance of these cells correlates with enhanced upregulation of hematopoiesis. The role of proliferative cells in postburn immune changes has not been directly tested. Gemcitabine, a ribonucleotide reductase inhibitor, has been shown to deplete proliferative immature myeloid cells in tumor models while sparing mature cells, leading to restored lymphocyte function and tumor regression. We treated burn mice at postburn day 6 (PBD6) with 120 mg/kg gemcitabine. On PBD8, splenocytes were taken and stimulated with LPS, peptidoglycan, or concanavalin A. The blood and spleen cell populations were enumerated by flow cytometry or automated cell counter. In addition, mice treated with gemcitabine were given LPS or infected with Pseudomonas aeruginosa at PBD8, and mortality was monitored. Gemcitabine depleted burn-induced polymorphonuclear leukocytes and inflammatory monocytes without affecting mature F4/80 macrophages. This was accompanied by reduced TNFα, IL-6, and IL-10 production by burn splenocytes. Burn splenocytes stimulated with mitogens exhibited increased nitric oxide production relative to sham mice. In vivo treatment of burn mice with gemcitabine blocked these burn-induced changes without damaging lymphocyte function. Treatment of burn mice with gemcitabine ameliorated burn-induced susceptibility to LPS and infiltration of polymorphonuclear leukocytes into the liver and lung. Finally, gemcitabine treatment blocked the protective effect of burn injury upon P. aeruginosa infection. Our report shows that proliferative cells are major drivers of postburn immune changes and provides evidence that implicates immature myeloid cells in these processes.

Association of high mobility group box-1 protein levels with sepsis and outcome of severely burned patients

BackgroundThe study was performed to observe the systemic release and kinetics of high mobility group box-1 protein (HMGB1) in burned patients. Methods106 patients were included, and they were divided into three groups with different burn sizes: group I, group II and group III. Healthy volunteers served as normal controls (n=25). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The blood samples were used to detect levels of HMGB1 in plasma by ELISA kits for human. Gene expression of HMGB1 in peripheral blood mononuclear cells was assessed by real-time quantitative PCR taking GAPDH as the internal standard. ResultsThe levels of HMGB1 were significantly elevated on PBD 1–21 in patients with various burn sizes compared with normal controls, and there were obvious differences between group I and group III. The HMGB1 levels were significantly higher in septic patients than those without sepsis on PBD 7–21. Among septic patients, the HMGB1 levels in the survival group were markedly lower than those with fatal outcome on PBD 3–21. ConclusionsExtensive burn injury could result in significantly increased HMGB1 levels, which appears to be associated with the development of sepsis and fatal outcome of major burns.