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Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.

Summary Background & aims Poor outcomes can result from inadequate energy intake. We aimed to investigate the reliability of resting energy expenditure (REE) measured by indirect calorimetry (IC) with REE calculated using predictive equations for nutritional support in patients with major burns. Methods REE was measured using IC and compared with predictive equations in 215 adult severe burns patients from Jan 2011 to Jun 2015. Agreement between IC and predictive equations was assessed using Bland–Altman methods. Results All predictive equations, including newly developed Hangang equation, were compared with REE measured using IC. The mean measured REE was 1712 kcal/d. Bland–Altman analysis showed that 1.2 times HBE, Thumb 25, and Ireton–Jones equations had higher accuracy and reliability. The concordance correlation coefficient was higher (0.49) in the Ireton–Jones equation, and root mean square error (RMSE) was lowest (471.5) in the Thumb 25 equation. The proportion of patients with predicted REE within ±10% of measured REE was highest with Thumb 25 (52.5%). In the validation set, the Hangang equation showed the highest Lin's concordance correlation coefficient (0.67) and the lowest RMSE (311.4). Other equations for burns patients had higher mean bias and overestimated REE when compared with IC results. Conclusions This study suggests that Thumb 25 can be used as an alternative method for estimating energy requirements of patients with major burns when IC is not available or applicable. However, for these patients with significant variation in metabolism over time, an alternative equation is the new Hangang equation.

OBJECTIVE: To evaluate the efficacy of fibrin sealant as a topical hemostatic agent and for graft fixation during skin grafting of hand burns. METHODS: This prospective cohort study enrolled 40 patients with hand burns from January 2013 to December 2016. They were all treated with excision and split-thickness skin graft and divided into the fibrin sealant with tourniquet group (20 patients) and epinephrine tumescence group (20 patients). MAIN OUTCOME MEASURES: Demographic and clinical data such as age, sex, burn characteristics, operation time, estimated blood loss, and take rate were collected from each patient. MAIN RESULTS: The demographic and burn characteristics were not statistically different between the two groups. Estimated blood loss per cm2 (0.30 vs 1.00; P < .001) was significantly lower and the graft take rate (99.2% vs 98.2%; P = .032) was significantly higher in the fibrin sealant with tourniquet group. CONCLUSIONS: The use of fibrin sealants accompanied by tourniquets for hand burns exhibited superior results in terms of decreasing blood loss and had a better graft take rate compared with treatment with epinephrine tumescence.

Additional file 1: Supplementary Table 1. Time varying Performance of baseline biomarkers using ID approach (AUC with 95% CI).

Additional file 2: Supplementary Table 2. Time varying Performance of updated biomarker using ID approach (AUC with 95% CI).

Additional file 4: Supplementary Table 4. Time varying Performance of updated biomarker using CD approach (AUC with 95% CI).

Additional file 3: Supplementary Table 3. Time varying Performance of baseline biomarkers using CD approach (AUC with 95% CI).

Background The progression of biomarkers over time is considered an indicator of disease progression and helps in the early detection of disease, thereby reducing disease-related mortality. Their ability to predict outcomes has been evaluated using conventional cross-sectional methods. This study investigated the prognostic performance of biomarkers over time. Methods Patients aged > 18 years admitted to the burn intensive care unit within 24 h of a burn incident were enrolled. Information regarding longitudinal biomarkers, including white blood cells; platelet count; lactate, creatinine, and total bilirubin levels; and prothrombin time (PT), were retrieved from a clinical database. Time-dependent receiver operating characteristic curves using cumulative/dynamic and incident/dynamic (ID) approaches were used to evaluate prognostic performance. Results Overall, 2259 patients were included and divided into survival and non-survival groups. By determining the area under the curve using the ID approach, platelets showed the highest c-index [0.930 (0.919–0.941)] across all time points. Conversely, the c-index of PT and creatinine levels were 0.862 (0.843–0.881) and 0.828 (0.809–0.848), respectively. Conclusions Platelet count was the best prognostic marker, followed by PT. Total bilirubin and creatinine levels also showed good prognostic ability. Although lactate was a strong predictor, it showed relatively poor prognostic performance in burns patients.

This study aimed to investigate the differences in the trajectory of blood biomarkers routinely assessed through forward- and backward-looking approaches among burn patients. This cohort study included patients above 18 years of age from February 2007 to December 2018. All the biomarkers were estimated from admission to discharge from the intensive care unit. Significant differences were observed in the platelet count at 40 days, prothrombin time (PT) at 32 days, white blood cell count at 26 days, creatinine levels at 22 days, and lactate and total bilirubin levels at 19 days before death. In reverse order, significant differences were observed in the fitted model in platelet count at 44 days and in the platelet count and PT at 33 days. We obtained more valuable information from the longitudinal biomarker trajectory using the backward-looking method than using the forward-looking method. The platelet count served as the earliest predictor of mortality among burn patients.

This study aimed at identifying properties of cryopreserved acellular dermal matrix (CPADM) and evaluating its effectiveness in the treatment of burn patients. The prospective study included 50 patients who received split-thickness skin grafts with CPADM over joints between January 2010 and July 2012. From June to October 2014, a total of 11 patients revisited our burn clinic for evaluation of the range of motion (ROM) of the joints in the involved areas. Additionally, an assessment of the condition of the grafted skin was made with regard to skin elasticity, transepidermal water loss (TEWL), and melanin and erythema levels. 19 of 50 patients who received CPADM and 31 of the 64 patients who received a freeze-dried acellular dermal matrix (FDADM) agreed to undergo analysis of the conditions of their scars. The CPADM was introduced in 2009. It was created using a controlled-rate freezer with a cryopreservation solution and was evaluated with regard to its tensile strengths and angiogenic factor release. In all, 53.8% of patients who had received the CPADM application had no ROM limitations afterwards. The TEWL in the CPADM-grafted areas was similar to that in normal skin; however, there was significantly less elasticity and higher melanin and erythema values in the grafted areas than in normal skin. Application of CPADM was more effective than that of FDADM in terms of scar thickness, elasticity, and TEWL levels (0.13±0.04 vs. 0.2±0.1 cm, 0.67±0.27 vs. 0.456±0.48 mm, and 16.2±6.8 vs. 12.1±5.3 g/h/m2, respectively). Therefore, the CPADM for split-thickness skin grafts is a safe and effective dermal replacement for one-stage surgery in patients with acute burns.

OBJECTIVE To retest the safety and effectiveness of a thermosensitive hydrogel-type cultured epithelial allograft (KeraHeal-Allo; MCTT, Seoul, South Korea) and identify the subjective experience of patients and doctors with this product. DESIGN AND SETTING Prospective interventional phase 3 study in 3 burn centers near Seoul, South Korea. PATIENTS Thirty-three patients with deep second-degree burns larger than 200 cm (for intervention and control sites of 100 cm each) were enrolled. INTERVENTION A cultured epithelial allograft containing 2 × 10/1.5 mL keratinocytes was applied to each patient's intervention site. Three principal investigators (1 in each institution) evaluated the effectiveness of the allograft at their institution and the others'. Researchers administered a subjective satisfaction survey during each patient's last visit. MAIN OUTCOME MEASURE The primary end point of the study was the re-epithelialization period. MAIN RESULTS The re-epithelialization period for the intervention was 2.8 ± 2.2 days faster than that of control sites at other institutions (P < .001) and 2.5 ± 3.4 days faster than that of control sites in the same institution (P < .001). There were no reported adverse events. Satisfaction scores provided by patients and doctors showed significantly high scores on all items. CONCLUSUIONS This type of cultured epithelial allograft is safe and well received by patients and providers and promotes re-epithelialization.

s Background Acute kidney injury (AKI) is a critical complications in severely burned patients associated with high morbidity and mortality. The purpose of this study was to investigate the impact of severity of AKI at the time of continuous renal replacement therapy (CRRT) start on patient outcome and to identify the prognostic factors in severely burned patients with CRRT application. Methods From January 2007 to June 2010, 84 burn patients with more than 40% of total body surface area (TBSA) burned who treated with continuous renal replacement therapy for acute kidney injury were analyzed retrospectively. Results There was no significant difference of mortality by the severity of AKI at the time of CRRT start. However, the mean TBSA burned, abbreviated burn severity index, arterial pH, partial pressure of carbon dioxide (PaCO 2 ) and blood urea nitrogen (BUN)/creatinine (Cr) ratio had a statistical significance to predict mortality in receiver operation characteristic curve. In a multivariate logistic regression analysis, only sepsis had an independent association with mortality. Conclusions The severity of the AKI at the time of CRRT start did not have significant relationship with patient outcome. CRRT can be applied to minimize the complication of AKI including electrolyte imbalance and volume overload. Because only the presence of sepsis was independently associated with mortality, treatment for sepsis should be focused to improve the survival of the severely burned patients with CRRT.

Collagen sponges are often used as dermal substitutes in the treatment of burns, trauma, infections, and wounds. Dermal substitutes that can be applied in a one-stage operation are particularly important for dermal regeneration. Some protocols for the production of collagen sponges have been developed, but many issues remain, including low yield, contraction, and expense. In this study, the effectiveness of two skin substitutes was evaluated. Specifically, we compared two thin matrices, i.e., the newly developed INSUREGRAF® 1.2 mm and the widely used Matriderm® 1 mm Single Layer, with respect to their biochemical and mechanical properties, safety, and efficacy. We examined the rate of contractibility and biocompatibility using in vitro and in vivo models. The INSUREGRAF had an interconnected pore structure, which affects cell attachment and proper vascularization. Accordingly, this novel collagen sponge type has the potential to promote skin tissue regeneration and is especially suitable for full-thickness skin defects as a one-stage operation substitute.

Conventional collagen scaffolds, which were fabricated like spongy types, have been used widely to promote wound repair since they can enhance various cellular activities including cell proliferation and migration, and even guidance of near cells to work as normal tissues functionally. Fabrication technology of 3 dimensional (3D) scaffolds including solid free-form fabrication and rapid prototyping methods is developing all the time in order to promote wound repair efficiently. In addition, researchers have been studying scaffolds containing other components, such as various cells, growth factors and related materials. In this study, we modified rapid prototyping methods and then set up a cell printing system, which is able to fabricate 3D cell-laden scaffolds for better skin tissue regeneration. These scaffolds have a layered structure and were manufactured using collagen, having optimal biocompatibility, and human primary skin cells including epidermal keratinocytes and dermal fibroblasts. Accordingly, these scaffolds are capable of proliferation and migration of keratinocytes and fibroblasts effectively. Therefore, we suggest that these cell-laden scaffolds can be used as engineered skin substitute (in other words, artificial skin), sufficiently.

Objectives We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis. Design This was retrospective cohort study. Setting The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea. Patients A total of 1,185 adult patients (mean age, 49.1 yr) were admitted between January 2009 and December 2015. Interventions The 1,185 patients enrolled in the present study and were then re-evaluated based on S1, burn sepsis, and S3 criteria, following which 565 patients, 812 patients, and 809 patients were diagnosed with sepsis based on S1, burn sepsis, S3 criteria, respectively. Measurements and main results For diagnostic performance, sensitivity, specificity, predictive value, and likelihood ratio were calculated. The area under the curve of the receiver operating characteristic curve was calculated to determine the accuracy of mortality prediction. The optimal cutoff value of Sequential Organ Failure Assessment score was calculated by the decision tree method. Total body surface area burned was 33.4%. Patients were identified with sepsis using S1 (812), S3 (809), and burn sepsis (565) criteria. Overall mortality was 20.3%, highest (82.2%) and lowest (26.5%) occurred with new septic shock (SH3) and S3, respectively. The sensitivity and specificity for burn sepsis (84.6% and 61.8%) and SH3 (63.1% and 96.5%) were reported. Area under the curve values for Sequential Organ Failure Assessment scores were the highest in all sepsis categories. With Sequential Organ Failure Assessment score greater than or equal to 6 (with infection), the accuracy was 0.86 (95% CI, 0.82-0.89). Conclusions The S3 criteria failed to show superior prognostic accuracy for mortality in severely burned patients. Sequential Organ Failure Assessment score greater than or equal to 6 may be a better criterion for the diagnosis of sepsis in burns patients.

Background Diagnosing acute kidney injury quickly is imperative since it is known as an independent risk factor for mortality in burn patients. We evaluated the diagnostic power of creatinine, cystatin, serum and urine neutrophil gelatinase-associated lipocalin at different time periods and observed the changes from baseline for each biomarker. Methods This was a prospective observation study from January 2015 to February 2016. A total of 84 patients were enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th, 21st, and 28th days after admission. All samples were collected until acute kidney injury developed. Results Acute kidney injury developed in 35 patients. The mean age was 49.6 years with a male predominance. The median urine neutrophil gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88 mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL) on the 14th day. The area under the curve of creatinine levels was the highest with 0.857 during the 1st week. The area under the curve of urine neutrophil gelatinase-associated lipocalin was the highest with 0.803 during the 5th week. Conclusions Within 1 week of acute kidney injury, creatinine level was the optimal biomarker for diagnosis while urine neutrophil gelatinase-associated lipocalin showed better diagnostic performance following the 4- week period.

Background Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. Methods A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. Results The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). Conclusion Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery., Graphical Abstract

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006-2013, total 177 massive-burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi-square test. Multivariate logistic regression, Kaplan-Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft-application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet-type and spray-type CEA groups. Allograft application (odds ratio, 4.44; p

PURPOSE: To determine epidemiological trends among burns patients admitted to our burns center during 2003-2012, and the usefulness of the Abbreviated Burns Severity Index (ABSI) for predicting burns-related mortality. METHODS: We retrospectively reviewed the data of 4481 burns patients. We analyzed the epidemiological trends and ABSI scores using Student t-test and one-way analysis of variance (continuous variables), chi-square test (categorical variables) and stepwise logistic-regression analysis (predictors of mortality). RESULTS: The mean age and male-to-female ratio were 39.9±19.7 years and 2.88, respectively. ABSI scores decreased from 7.7±3.0 in 2003 to 6.9±3.0 in 2012. Mortality rate improved from 24.5% in 2003 to 15.8% in 2012. Burns were caused by flames (67.3%), scalding (22.0%) and electrical (7.5%), chemical (1.6%) and contact (1.5%) injuries. Scalding and flames were the most common causes in patients aged ≤20 years and ≥21 years, respectively. Female sex, inhalation injury, full-thickness burns, large total body surface area (TBSA) burned and old age predicted mortality. ABSI scores 14 were associated with 0.7% and >90% mortality, respectively. CONCLUSIONS: The mortality of major burns has decreased but remains high. ABSI scores predict burns-related mortality. Language: en

Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA) burned, and inhalation injury) and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio) by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p

The purpose of this study was to assess the plasma neutrophil gelatinase-associated lipocalin (NGAL) for early detection of acute kidney injury (AKI) and prediction of mortality in severely burned patients. From January 2014 to September 2015, 76 consecutive patients with more than 20% of TBSA burned were enrolled. Blood samples for plasma NGAL were collected at 0, 7, 14, 21, and 28 days after admission and analyzed with injury severity, clinical outcome, and AKI development. Plasma NGAL was significantly affected by the TBSA burned, AKI, and mortality, and it was significantly increased after operation and septic shock. Plasma NGAL was significantly increased within 7 days before AKI development in total patients (P < .001) and septic shock patients (P < .001) but not significantly increased in patients without septic shock (P = .167). Though, in a receiver operating characteristic curve analysis for predicting AKI, continuous renal replacement therapy application, and mortality, plasma NGAL was statistically significant; plasma NGAL was not independently associated with mortality in a multivariate logistic regression analysis. Plasma NGAL should be interpreted carefully in the major burn patients because it can reflect both inflammatory condition and AKI.

Purpose The purpose of this study was to develop a new prediction model to reflect the risk of mortality and severity of disease and to evaluate the ability of the developed model to predict mortality among adult burn patients. Methods This study included 2009 patients aged more than 18 years who were admitted to the intensive care unit (ICU) within 24 hours after a burn. We divided the patients into two groups; those admitted from January 2007 to December 2013 were included in the derivation group and those admitted from January 2014 to September 2017 were included in the validation group. Shrinkage methods with 10-folds cross-validation were performed to identify variables and limit overfitting of the model. The discrimination was analyzed using the area under the curve (AUC) of the receiver operating characteristic curve. The Brier score, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were also calculated. The calibration was analyzed using the Hosmer-Lemeshow goodness-of-fit test (HL test). The clinical usefulness was evaluated using a decision-curve analysis. Results The Hangang model showed good calibration with the HL test (χ2 = 8.785, p = 0.361); the highest AUC and the lowest Brier score were 0.943 and 0.068, respectively. The NRI and IDI were 0.124 (p-value = 0.003) and 0.079 (p-value

The purpose of this study is to clarify the clinical significance of serum transthyretin (TTR) in massively burned patients in nutrition support and clinical severity.A retrospective study was performed with 204 patients admitted to Hangang Sacred Heart Hospital's Burn Center September 2010-September 2012 with burn wounds20% of total body surface area (TBSA) burned. Serum TTR, C-reactive protein (CRP), lactic acid, and an NST index (calculated by dividing real caloric intake by estimated caloric need for 7 days) were analyzed on a weekly basis for 5 weeks after admission.When we classified patients with severity according to mortality, percentage of TBSA burned, serum lactic acid, and CRP, mean serum TTR level was significantly higher in the less severe patient group than in the severe patient group in each week for every severity index. And the serum TTR level did not show significant differences by NST index in both the severe patient group and the less severe patient group. In a multivariate logistic regression, percentage TBSA burned, TTR, and lactic acid had an independent association with mortality.Serum TTR did not show a significant difference by nutrition support in massively burned patients with20% of TBSA burned. But serum TTR was significantly different by the severity of the patient and independently associated with mortality. Hence, serum TTR level can be 1 of the useful biomarkers for comprehending the severity of the illness in massively burned patients.

The pharmacokinetic (PK) property of fluconazole might be significantly altered in major burn patients by medical interventions and physiologic changes. In this study, our aims were to investigate fluconazole PK in burn patients using a population approach and to recommend the optimal fluconazole regimen based upon the predicted therapeutic outcome. At steady state, blood samples for PK analysis were obtained from 60 burn patients receiving between 100 and ∼400 mg fluconazole daily. A mixed-effect modeling was performed and the therapeutic outcome of antifungal therapy was predicted for 10,000 virtual patients using NONMEM (version 7.2). MIC values were sampled from the MIC distribution at the study site. An area under the free drug concentration-time curve (fAUC)/MIC measurement of >25 h was used as the criterion for therapeutic success. When the same dose was given, the plasma concentration of fluconazole was predicted to be lower in burn patients compared to the nonburn population because of the large PK parameter (clearance, volume of distribution) estimates and continuous renal replacement therapy (CRRT). This tendency was particularly predominant when the patients were within 30 postburn days. Based upon our findings, 400 mg/day fluconazole is recommended to obtain therapeutic successes in major burn patients.

Background Major burn injury induces an inflammatory response that is accompanied by the release of various cytokines. We investigated the gradual changes in the levels of pro-inflammatory and anti-inflammatory cytokines following burn injury and determined the relationship between these levels and burn size in adult Korean patients with burn injury. Methods Blood samples from 9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7, 14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF) were measured. Burn patients were divided into 3 groups according to burn size (15-30%, 31-50%, >50% total body surface area), and the concentrations of the cytokines were compared between these groups and the control group over 3 weeks. Results Compared to their levels in controls, IL-6, IL-8, IL-10, TNF-α, and G-CSF levels in burn patients were significantly higher during the observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time point increased with burn size, although peak levels and time to peak levels of these cytokines differed from patient to patient. Conclusions These findings indicate that IL-6, IL-8, IL-10, TNF-α, and G-CSF are important mediators in inflammatory changes after burn injury; however, various factors, including burn size, may influence the concentrations of these cytokines.

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases.

In efforts to prevent and reduce joint contracture and scar formation after burn, we used the acellular human dermis (AlloDerm) as a dermal replacement in the acute stage. A total of 64 patients received AlloDerm graft selectively on joint areas during the study period from March, 2005 to July, 2007. From January to March, 2008, a total of 31 patients returned to our burn center to examine the functional results by measuring range of motion of joints. Additionally, the quality of grafted skin condition criteria of skin elasticity, scar thickness, trans-epidermal water loss, melanin and erythema level was measured in a total of 11 patients among them. By analyzing the limitation level of 55 joints excluding hand areas, we found that 24 joints (43.6%) showed no limitations, 12 joints (21.8%) showed limitations below 10%, 16 joints (29.1%) showed limitations between 10 and 19% and 3 joints (5.5%) showed limitations over 20%. The scar thickness of non-AlloDerm applied areas was 2.5+/-0.9 mm and AlloDerm applied areas was 1.8+/-0.7 mm (p = 0.396). Trans-epidermal water loss for non-AlloDerm applied areas was 20.9+/-7.7 g/h/m(2) and AlloDerm applied areas was 10.8+/-3.4 g/h/m(2) (p

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006-2013, total 177 massive-burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi-square test. Multivariate logistic regression, Kaplan-Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft-application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet-type and spray-type CEA groups. Allograft application (odds ratio, 4.44; p 0.01) significantly influenced CEA application. The CEA group showed significantly higher survival rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p = 0.02) and 0.59 (p = 0.05) according to the uni- and multivariate Cox regression analysis, respectively. In conclusion, early and aggressive allograft application is required to facilitate CEA application. Furthermore, the use of CEAs was associated with a lower mortality, but this result should be interpreted with caution as the groups were not randomized.

Background This study was aimed at evaluating the effectiveness of serum cystatin C and microalbuminuria as diagnostic markers for acute kidney injury (AKI) in major burn patients. Materials and methods Major burn adult patients admitted to the burn intensive care unit within 24 h from the onset of injury were enrolled. Serum cystatin C and microalbuminuria (albumin–creatinine ratio, ACR) were obtained at postburn days 1, 3, 7, 14, 21 and 28. The patients were divided into two groups of the AKI group and the nonacute kidney injury group. Results A total of 97 patients were enrolled in this study. Acute kidney injury was diagnosed in 40 patients (41·2%) at postburn day 17·3 ± 7·9. The area under the curve of the receiver operating characteristic curve for serum cystatin C was 0·808 (95% CI, 0·711–0·905, P

This study is a phase 1 and 2 clinical trial for investigating the safety profile, effective treatment dose and effectiveness of the newly developed thermosensitive hydrogel-type cultured epidermal allograft. For phase 1, the keratinocytes were divided into 3 groups as follows, with 5 patients in each group: (1) low-dose group (6.7×10(6)/1.5mL), (2) medium-dose group (2×10(7)/1.5mL), and (3) high-dose group (6.0×10(7)/1.5mL). The second phase of the trial proceeded with 10 cases after choosing the most effective dose based on the analysis of the first phase. When comparing re-epithelialization time, medium- and high-dose group showed significantly shorter re-epithelialization time than low-dose group (p=0.003 and p=0.002). A total of 15 cases, 5 cases selected from phase 1 and 10 cases test in phase 2 with the medium dose, were compared with the re-epithelialization period. The re-epithelialization period was 9.6±4.0 days in the test site and 12.4±4.8 days in the control site. In the test site, re-epithelialization was 2.8±1.8 days faster than in the control site (p

a b s t r a c t Objective: To evaluate the effect of burn rehabilitation massage therapy on hypertrophic scar after burn. Method: One hundred and forty-six burn patients with hypertrophic scar(s) were randomly divided into an experimental group and a control group. All patients received standard rehabilitation therapy for hypertrophic scars and 76 patients (massage group) additionally received burn scar rehabilitation massage therapy. Both before and after the treatment, we determined the scores of visual analog scale (VAS) and itching scale and assessed the scar characteristics of thickness, melanin, erythema, transepidermal water loss (TEWL), sebum, and elasticity by using ultrasonography, Mexameter 1 , Tewameter 1 , Sebumeter 1 , and Cutometer 1 , respectively. Results: The scores of both VAS and itching scale decreased significantly in both groups, indicating a significant intragroup difference. With regard to the scar characteristics, the massage group showed a significant decrease after treatment in scar thickness, melanin, erythema, TEWL and a significant intergroup difference. In terms of scar elasticity, a significant intergroup difference was noted in immediate distension and gross skin elasticity, while the massage group significant improvement in skin distensibility, immediate distension, immediate retraction, and delayed distension. Conclusion: Our results suggest that burn rehabilitation massage therapy is effective in improving pain, pruritus, and scar characteristics in hypertrophic scars after burn.

Background: Extracorporeal shock wave therapy (ESWT) has been used to reduce pain in patients with various musculoskeletal diseases and wounds. We investigated the effect of ESWT on scar pain after complete wound epithelialization in burn patients. Methods: A prospective, single-blind, placebo-controlled study was conducted from February 2014 to 2015. Forty patients with burn scar pain despite standard therapy (medication, physical therapy, and burn rehabilitation massage therapy) were randomized into ESWT or control (sham ESWT) groups. ESWT was administered at 100 impulses/cm2 (0.05–0.15 mJ/mm2) once per week for 3 weeks. The treatment effects were assessed using the numerical rating scale (NRS), pain threshold, Nirschl pain phase system, and Roles and Maudsley scores. Results: The characteristics of patients between the 2 study groups were balanced (P >0.05) for age, sex, and total burn surface area (%). In both groups, the NRS, pain threshold (Ib/cm2), and Nirschl pain phase system values significantly improved (P

BACKGROUND Hypophosphatemia is relatively common phenomenon in patients with massive burn injury. Therefore, we check serum phosphate level routinely and try to supply phosphate in a timely manner. The purpose of this study was to investigate the change of the serum phosphate level of early postburn period and the impact of hypophosphatemia on the prognosis of patients. METHODS A total of 227 patients with burn injury were reviewed retrospectively. We performed analysis of serum phosphate level within 20 days from burn injury. RESULTS Patients' mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate < 1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia (1.0 ≤ phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore, overall incidence of hypophosphatemia was 66.4%. There was no significant difference in serum phosphate level with survival, total body surface area burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence interval [CI], 1.025-9.871; p = 0.045), total body surface area burned (OR, 20.934; 95% CI, 6.845-64.024; p = 0.000), and mechanical ventilation (OR, 5.581; 95% CI, 2.380-13.085; p = 0.002) were independently associated with mortality. However, serum phosphate level (OR, 0.828; 95% CI, 0.275-2.495; p = 0.737) does not have a statistical significance. CONCLUSION Although multiple studies have evaluated the efficacy and safety of phosphate repletion regimens, the effect on mortality and morbidity is not well reported. However, our results show that patients with massive burn injury have high incidence of hypophosphatemia, and hypophosphatemia can result in many complications. Therefore, routine check and supply of phosphate can be suggested in patients with massive burn injury. LEVEL OF EVIDENCE Prognostic study, level II.

We observed that serum transthyretin (TTR) levels consistently remain low when patients' general conditions are poor, despite adequate nutritional support. We conducted this study to analyze the changes of serum TTR over time from injury in massively-burned patients and verify the validity of prediction by clinical outcomes, which are assessed via serum TTR in the early postburn period.From January 2005 to December 2010, the samples of serum TTR from 471 burn patients (mean % total body surface area [TBSA] burned, 51% ± 20%) were analyzed with time frames from injury retrospectively.Serum TTR significantly decreased during the period from day 5 to day 10 postinjury in both the survival group (n = 290, mean %TBSA burned, 42.9% ± 14.2%) and nonsurvival group (n = 181, mean %TBSA burned, 64.6% ± 20.8%). However, after this period, the serum TTR constantly increased in the survival group but remained low in nonsurvivors. At all time, the levels of serum TTR obtained from survivors were significantly higher than those of nonsurvivors. The serum TTR had weak correlation with the extent of the burn injury (r = -0.234). Survival rates of the patients increased significantly by the increase of the serum TTR of early postburn period. In multivariable model, age (odds ratio [OR], 1.054; 95% confidence interval [CI], 1.043-1.066; p = 0.000), TBSA burned (OR, 1.058; 95% CI, 1.051-1.066; p = 0.000), sex (OR, 0.720; 95% CI, 0.547-0.947; p = 0.019), and serum TTR during early postburn period (OR, 1.05; 95% CI, 0.873-0.972; p = 0.003) were independently associated with mortality.The serum TTR of early postburn period can be used as a prognostic markers, and low serum TTR can be used as a signal for screening out the patients at risk who need careful assessment and monitoring at an early stage.

OBJECTIVES: To develop a population pharmacokinetic model of meropenem in burn patients and to explore the appropriateness of current dosage regimens. PATIENTS AND METHODS: Fifty-nine patients with burns ranging from 3% to 97% of total body surface area treated with meropenem were analysed. The population pharmacokinetic parameters of meropenem in 59 burn patients were estimated, and concentrations were simulated by using a mixed effect method (NONMEM, ver. 6.2). RESULTS: The final model was a two-compartment model with first-order elimination where creatinine clearance (CL(CR)) and oedema contributed. The mean population pharmacokinetic parameters were clearance (L/h) =4.45 +10.5 × CL(CR) (mL/min)/138, V1 (central volume) =17.0+11.1 × presence of oedema (0 or 1) L, V2 (peripheral volume) =10.1 L and Q (intercompartmental clearance) =5.25 L/h with interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated), respectively. CONCLUSIONS: The population clearance and volume of distribution in our burn patients were significantly greater than those reported in non-burn patients. The simulation of 1000 virtual patients' plasma meropenem concentration treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted the probability of achieving the time above MIC >40% of the dosing interval as 58.9% for Pseudomonas aeruginosa isolated from three university hospitals in Korea.

Purpose: Acute kidney injury (AKI) in major burn patients is a common complication with high morbidity and mortality. The mainstream treatment is early diagnosis and rapid termination and prevention of the underlying insult. Therefore, it’s essential to identify early biomarkers predicting AKI. Methods: A total of 85 patients who were admitted to the burn intensive care unit from June 2012 to July 2013 were included in this prospective cohort study. Ten biomarkers (blood urea nitrogen, serum creatinine, urine creatinine, cystatin C, cystatin C glomerular filtration rate, AST, lacate dehydrogenase [LD], creatine kinase, lactic acid, and myoglobin) were obtained at time of admission and evaluated as diagnostic biomarkers to predicting AKI and early AKI. Results: Out of 85 patients, 35 patients were dead and overall mortality was 41.2%. The mean age was 49.4 years and mean percentage of total body surface area was 53.2%. Area under the curve (AUC) of receiver operating characteristic curve of biomarkers on predicting AKI were 0.746, 0.718, and 0.717 in LD, lactic acid, and serum creatinine, respectively. AUC of cystatin C predicting AKI was much lower at 0.555. AUC of biomarkers on predicting early AKI were 0.833, 0.816, 0.790, and 0.759 in LD, serum creatinine, AST, and serum myoglobin. Conclusion: LD, lactic acid and serum creatinine were acceptable as diagnostic biomarkers of AKI and LD, serum creatinine, AST, and serum myoglobin were reasonable as diagnostic biomarkers of early AKI. However, cystatin C was an unfavorable biomarker in major burn patients.

Introduction The reported mortality rates range from 28% to 100% in burn patients who develop acute kidney injury (AKI) and from 50% to 100% among such patients treated with renal replacement therapy. Recently, the serum cystatin C and plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels have been introduced as early biomarkers for AKI; the levels of these biomarkers are known to increase 24 to 48 hours before the serum creatinine levels increase. In this study, we aimed to estimate the diagnostic utility of the cystatin C and plasma and urine NGAL levels in the early post-burn period as biomarkers for predicting AKI and mortality in patients with major burn injuries. Methods From May 2011 to July 2012, 90 consecutive patients with a burn wound area comprising ≥ 20% of the total body surface area (TBSA) were enrolled in this study. Whole blood and urine samples were obtained for measuring the serum creatinine, serum cystatin C, and urine and plasma NGAL levels at 0, 3, 6, 12, 24, and 48 hours after admission. Receiver operating characteristic curve, area under the curve, and multivariate logistic regression analyses were performed to assess the predictive values of these biomarkers for AKI and mortality. Results In the multivariate logistic regression analysis, all variables, including age, percentage TBSA burned, sex, inhalation injury, and serum creatinine levels, serum cystatin C levels, and plasma and urine NGAL levels were independently associated with AKI development. Moreover, age, sex, percentage TBSA burned, and plasma and urine NGAL levels were independently associated with mortality. However, inhalation injury and the serum creatinine and cystatin C levels were not independently associated with mortality. Conclusions Massively burned patients who maintained high plasma and urine NGAL levels until 12 hours after admission were at the risk of developing early AKI and early mortality with burn shock. However, the plasma and urine NGAL levels in the early post-burn period failed to predict late AKI and non-burn shock mortality in this study. Nevertheless, the plasma and urine NGAL levels were independently associated with AKI development and mortality within 48 hours after admission.

Purpose: The aim of this study was to elucidate whether plasma lactate (PL) and base deficit (BD) are useful early parameters to predict the prognosis of burn patients with inhalation injury. In addition, one of the main objectives was to evaluate if PL and its change, BD and its change due to fluid resuscitation, adds additional information. Methods: A retrospective review was performed on 151 patients admitted to our burn intensive care unit who were suspected to have inhalation burn injury, and then were confirmed by fibreoptic bronchoscopy between 1 Jan 2008 and 31 Dec 2008. All patients received proper fluid and electrolyte resuscitation, pain management, nutritional support, wound care and surgical debridement of dead tissue by burn surgeon. Results: Initial PL, PL1 (24 hours later) and initial BD show statistical differences between survivors group and non-survivors group. A better chance of survival occurs when resuscitation results in normal PL values within 24 h. Moreover, an outcome predictor of shock and effective resuscitation could be defined by evaluating the changes of BD on Day 1. Normalization of the BD within 24 h is associated with a better chance of survival. Conclusion: Measuring PL, BD and their changes may help to identify burn patients either for adequacy of treatment, or selection of other therapeutic options. Therefore titration of burn resuscitation to normalize PL and BD levels may be a reasonable method to improve burn mortality.

Purpose: Inhalation injury is one of the most severe morbidity and mortality factors in burn patients. The purpose of this study is to analyze the impact of inhalation injury to the prognosis of burn patients and to investigate the relationship between the inhalation injury assessment and the prognosis of patients. Methods: Bronchoscopy was performed in 170 patients who had the suspicion of inhalation injury and the patients were reviewed retrospectively from January 2008 to December 2009. Mortality was compared between the factors of brochoscopic findings, age, total body surface area (TBSA) burned, carboxyhemoglobin (COHb) level, PaO2/FiO2 (P/F) ratio. Results: Of 170 patients, 28 patients had no inhalation bronchoscopic finding. 109 patients had mild inhalation, 31 patients had moderate inhalation, only 2 patients had severe inhalation findings. The patients of moderate and severe inhalation findings had higher mortality (48.5%) than mild inhalation patients (31.1%). The larger total burnsurface area in inhalation patients, the greater the mortality. When compared to total admitted burn patients during the same period, inhalation patients showed higher mortality in the patients between 10 to 40% total burn surface area. Inhalation patients whose P/F ratio was below 300 showed higher mortality than above 300. But inhalation patients whose COHb level was below 1.5 had no difference in mortality with patients above 1.5. The COHb level and P/F ratio was the statistically different factors between inhalation patients and non-inhalation group in the mortality. Conclusion: Bronchoscopic findings, age, TBSA burned, P/F ratio were related with mortality in inhalation patients. When the international standardization of bronchoscopic classification developed, it can be possible to assess the inhalation patients more objectively and that will lead to the advancement in inhalation treatment and research.

Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), potentially life-threatening skin diseases with organ failures caused by drugs, require specialized intensive care. However, SJS and TEN have usually been managed in general wards and intensive care units by most doctors. This study describes the efficacy of treatment in the burn intensive care unit (BICU) compared to previous general treatments. Methods: To investigate the clinical features, outcomes and benefits of 11 patients with SJS and TEN treated in our burn intensive care unit. Data on 11 patients who were treated between January 2004 and December 2008 were collected via a retrospective chart review. Also, the data were reviewed with previous literatures on SJS and TEN treatments. Results: Patients were classified with overlap SJS/TEN (n=4, 36.36%) or TEN (n=7, 63.64%). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common causative agents. Hepatitis was the most common organ involvement in both overlap SJS/TEN (n=1, 9.1%) and TEN (n=4, 36.36%). Renal dysfunction (n=4, 36.36%) and respiratory disorders (n=3, 27.27%) were seen in some cases. Mean time of total reepithelization was 9 days and mean hospital day was 14.66 days. Two patients with TEN died from sepsis with multi-organ failure, and the mortality rate was 18.18%. Conclusion: Adequate treatment of SJS and TEN in the BICU supports efficacy with a low mortality rate, short healing time, short hospitalization and fewer complications.