Radiation exposure induces inflammasome pathway activation in immune cells.

Radiation exposure induces cell and tissue damage, causing local and systemic inflammatory responses. Because the inflammasome pathway is triggered by cell death and danger-associated molecular patterns, we hypothesized that the inflammasome may signal acute and chronic immune responses to radiation. Using a mouse radiation model, we show that radiation induces a dose-dependent increase in inflammasome activation in macrophages, dendritic cells, NK cells, T cells, and B cells as judged by cleaved caspase-1 detection in cells. Time course analysis showed the appearance of cleaved caspase-1 in cells by day 1 and sustained expression until day 7 after radiation. Also, cells showing inflammasome activation coexpressed the cell surface apoptosis marker annexin V. The role of caspase-1 as a trigger for hematopoietic cell losses after radiation was studied in caspase-1(-/-) mice. We found less radiation-induced cell apoptosis and immune cell loss in caspase-1(-/-) mice than in control mice. Next, we tested whether uric acid might mediate inflammasome activation in cells by treating mice with allopurinol and discovered that allopurinol treatment completely blocked caspase-1 activation in cells. Finally, we demonstrate that radiation-induced caspase-1 activation occurs by a Nod-like receptor family protein 3-independent mechanism because radiation-exposed Nlrp3(-/-) mice showed caspase-1 activation profiles that were indistinguishable from those of wild-type mice. In summary, our data demonstrate that inflammasome activation occurs in many immune cell types following radiation exposure and that allopurinol prevented radiation-induced inflammasome activation. These results suggest that targeting the inflammasome may help control radiation-induced inflammation.

A haemostatic technique using silicone gel dressing for burn surgery.

Significant blood loss and high rates of transfusion remain ongoing concerns in burn surgery. We have reported a haemostatic technique using silicone gel dressing to minimise bleeding during tangential excision in burn surgery. The purpose of this study was to identify the efficacy of our novel haemostatic technique for burn surgery. This study was a retrospective observational study. From 1 April 2011 to 31 March 2015, we collated data including pre- and 24-hour postoperative haemoglobin levels from patients over 15 years of age who underwent tangential excision for burn injuries. We also collected data on the amounts of measured blood loss, blood transfusions, excised areas, harvest areas and duration of surgeries. The collected data were divided into a conventional group and a silicone gel dressing group. Then, we analysed the differences between the two groups. During the study period, 357 patients were admitted to our burn centre, and 60 operations (44 patients) were performed by tangential excision. The conventional group comprised 28 operations (20 patients), and the silicone gel dressing group comprised 32 operations (26 patients). Excised areas and harvested areas were significantly larger in the silicone gel dressing group than in the conventional group. The amount of blood loss per percent excised and the number of units of blood transfused were significantly lower in the silicone gel dressing group. Duration of the surgeries was almost the same between the two groups. Application of our new technique during tangential excision for burn injuries resulted in a remarkable reduction in blood loss and transfusion requirements.

Systemic immune response of burns from the acute to chronic phase.

Immune responses that occur following burn injury comprise a series of reactions that are activated in response to damaged autologous tissues, followed by removal of damaged tissues and foreign pathogens such as invading bacteria, and tissue repair. These immune responses are considered to be programmed in living organisms. Developments of modern medicine have led to the saving of burned patients who could not be cured previously; however, the programmed response is no longer able to keep up, and various problems have arisen. This paper describes the mechanism of immune response specific to burn injury and the emerging concept of persistent inflammation, immunosuppression, and catabolism syndrome.

The timing of death in burn patients.

Aim: When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its underlying causes among burn patients. Methods: Patients evaluated were admitted to our burn center between January 2015, and December 2019. Patient information, time, and cause of death were retrospectively collected from their medical records. Results: Among 342 admitted patients, 49 died. The time of death was as follows: within 24 h (n = 9), within 3 days (n = 7), within 1 week (n = 5), within 2 weeks (n = 4), within 3 weeks (n = 3), within 30 days (n = 6), within 60 days (n = 5), and after 60 days (n = 9). The causes of death within 3 days were hypoxic encephalopathy, extensive burns (>80%), severe heat stroke, and acute coronary syndrome. The causes of death after 3 days were sepsis, pneumonia, intestinal ischemia, pancreatitis, and worsening of chronic diseases. The mortality rate was similar for patients ≥65 years of age and those with a burn area of ≥20%, with both groups showing a particularly poor prognosis. Conclusions: The timing of death in hospitalized burn patients showed a bimodal distribution as approximately 40% of patients who survived the resuscitation period died after 30 days. Elderly patients were at particularly high risk for mortality. In burn care, treatment planning should consider not only the short-term but also the long-term prognosis.

Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

Recent advancements in proteomics allow for the concurrent identification and quantification of multiple proteins. This study aimed to identify proteins associated with severe burn pathology and establish a clinically useful molecular pathology classification. In a retrospective observational study, blood samples were collected from severe burn patients. Proteins were measured using mass spectrometry, and prognosis-related proteins were extracted by comparing survivors and non-survivors. Enrichment and ROC analyses evaluated the extracted proteins, followed by latent class analysis. Measurements were performed on 83 burn patients. In the non-survivor group, ten proteins significantly changing on the day of injury were associated with metabolic processes and toxin responses. ROC analysis identified HBA1, TTR, and SERPINF2 with AUCs > 0.8 as predictors of 28-day mortality. Latent class analysis classified three molecular pathotypes, and plasma mass spectrometry revealed ten proteins associated with severe burn prognosis. Molecular pathotypes based on HBA1, TTR, and SERPINF2 significantly correlated with outcomes.

Prognostic impact of fecal pH in critically ill patients.

INTRODUCTION: We have reported that altered gut flora is associated with septic complications and eventual death in critically ill patients with systemic inflammatory response syndrome. It is unclear how fecal pH affects these patients. We sought to determine whether fecal pH can be used as an assessment tool for the clinical course of critically ill patients. METHODS: Four hundred ninety-one fecal samples were collected from 138 patients who were admitted to the Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Japan. These patients were treated in the intensive care unit for more than 2 days. Fecal pH, fecal organic acids, and fecal bacteria counts were measured and compared by survived group and nonsurvived group, or nonbacteremia group and bacteremia group. Logistic regression was used to estimate relations between fecal pH, age, sex, or APACHE II score and mortality, and incidence of bacteremia. Differences in fecal organic acids or fecal bacteria counts among acidic, neutral, and alkaline feces were analyzed. RESULTS: The increase of fecal pH 6.6 was significantly associated with the increased mortality (odds ratio, 2.46; 95% confidence interval, 1.25 to 4.82) or incidence of bacteremia (3.25; 1.67 to 6.30). Total organic acid was increased in acidic feces and decreased in alkaline feces. Lactic acid, succinic acid, and formic acid were the main contributors to acidity in acidic feces. In alkaline feces, acetic acid was significantly decreased. Propionic acid was markedly decreased in both acidic and alkaline feces compared with neutral feces. No differences were noted among the groups in bacterial counts. CONCLUSIONS: The data presented here demonstrate that the fecal pH range that extended beyond the normal range was associated with the clinical course and prognosis of critically ill patients.

Resistin forms a network with inflammatory cytokines and is associated with prognosis in major burns.

BACKGROUND: In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. METHODS: This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. RESULTS: Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. CONCLUSIONS: In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Growth Differentiation Factor-15 Correlates with Mortality and Severity in Severe Burns.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is expressed in almost all tissues of the body and is necessary for the body's defense response to stress such as inflammation. It has been reported to be associated with incidence and mortality in many diseases, including systemic inflammatory response syndromes. There are no reports on GDF-15 in burns. The purpose of this study was to investigate the trend of GDF-15 in blood in patients with severe burns and to determine its relationship with severity and mortality. METHODS: This was a retrospective, observational, single-center study. The level of GDF-15 in the blood was measured and compared with clinical parameters, including prognosis. Time points for sample collection were the day of injury, 4 days after injury, and 1 week after injury. RESULTS: Eighty-three patients were enrolled in the study. At all time points, GDF-15 levels in the nonsurvivor group were significantly higher than those in the survivor group. In the analysis using the ROC curve for 28-day survival, the AUC of the GDF-15 value on the day of injury was 0.798, which was higher than those of % total body surface area, burn index, and Sequential Organ Failure Assessment (SOFA) score. GDF-15 levels correlated positively with SOFA score, and the relationship became stronger along with the time course of severe burn. CONCLUSIONS: In the acute phase of severe burn, GDF-15 levels were associated with mortality and SOFA scores.

Patterns of Gram-stained fecal flora as a quick diagnostic marker in patients with severe SIRS.

BACKGROUND: The gut is an important target organ of injury during critically ill conditions. Although Gram staining is a common and quick method for identifying bacteria, its clinical application has not been fully evaluated in critically ill conditions. AIMS: This study's aims were to identify patterns of Gram-stained fecal flora and compare them to cultured bacterial counts and to investigate the association between the patterns and septic complications in patients with severe systemic inflammatory response syndrome (SIRS). METHODS: Fifty-two patients with SIRS were included whose Gram-stained fecal flora was classified into three patterns. In a diverse pattern, large numbers of multiple kinds of bacteria completely covered the field. In a single pattern, one specific kind of bacteria or fungi predominantly covered the field. In a depleted pattern, most bacteria were diminished in the field. RESULTS: In the analysis of fecal flora, the numbers of total obligate anaerobes in the depleted pattern was significantly lower than those in the diverse pattern and single pattern (p < 0.05). The concentrations of total organic acids, acetic acid, and propionic acid in the depleted pattern were significantly lower than those in diverse pattern and single pattern (p < 0.05). Mortality due to multiple organ dysfunction syndrome for the single pattern (52%) and the depleted pattern (64%) was significantly higher than that for the diverse pattern (6%) (p < 0.05). CONCLUSIONS: Gram-stained fecal flora can be classified into three patterns and are associated with both cultured bacterial counts and clinical information. Gram-stained fecal bacteria can be used as a quick bedside diagnostic marker for severe SIRS patients.

Good recovery without decompression fasciotomy for crush syndrome caused by using a Japanese-style toilet.

We report a case of crush syndrome that developed while the patient was squatting to use a Japanese-style toilet. The patient was a 61-year-old male with an obese body. He was sitting on the toilet and couldn't stand up, and after a few hours, the landlord found him and called the emergency services. On presentation, the patient was hyperkalemic and in shock, and his serum creatine kinase levels rose to a maximum of 287,600 U/L. He was diagnosed with postural crush syndrome in both lower extremities due to squatting position in a Japanese-style toilet. Subjective symptoms, physical examination, and blood tests were monitored and the patient was observed. As a result, the patient could be treated conservatively without fasciotomy. Dialysis was not necessary because the fluid infusion maintained adequate urine output and corrected the hyperkalemia. Magnetic resonance imaging of both lower extremities showed multiple high-signal areas in the muscles of the bilateral thighs and lower legs. This case suggested that if the wound is closed, the peripheral pulse is palpable, and the patient's symptoms have improved, a fasciotomy should not be performed. People who are too heavy to squat may need to be careful when using this kind of toilet.

Chest physical therapy reduces pneumonia following inhalation injury.

PURPOSE: The purpose of this study was to clarify the efficacy of chest physiotherapy (CPT) in patients with inhalation injury in the acute phase. PATIENTS AND METHODS: This was a single-institution retrospective study of patients with inhalation injury admitted to the Chukyo Hospital Burn Center from April 2004 to March 2014 who required endotracheal intubation for respiratory care. The patients were divided into two groups: the CPT group and the conventional physical therapy group. We compared the two groups according to the incidence of pneumonia, length of ICU/hospital stay, and level of activities of daily living at discharge. To match subject backgrounds, we conducted a propensity score matching analysis, and using a Cox regression analysis, we evaluated the effect of CPT on the first pneumonia event. RESULTS: Of 271 patients admitted to the burn center, 139 patients were included. The incidence of pneumonia in the CPT group was significantly lower and these patients required fewer days until they could sit on the edge of the bed compared with the conventional physical therapy group. In a Cox regression model, the hazard ratio for the first incidence of pneumonia in the CPT group vs. the conventional therapy group was 0.27 (95% confidence interval: 0.13-0.54, P = 0.0002) after propensity score matching. CONCLUSIONS: CPT reduces the incidence of pneumonia and facilitates patient mobilization following inhalation injury.

Comment on "volume-outcome relationship on survival and cost benefits in severe burn injury: a retrospective analysis of a Japanese nationwide administrative database" (Endo et al., Journal of Intensive Care 2019).

This is a critical comment on the paper by Endo et al. on the volume-outcome relationship on survival and cost benefits in severe burn injury which addresses biases related to patient transfer and burn severity assessment.

Impact of fecal short-chain fatty acids on prognosis in critically ill patients.

AIM: This study aimed to evaluate the relationship between fecal organic acids and mortality in critically ill patients. METHODS: This retrospective study included 128 patients who fulfilled the criteria of systemic inflammatory response syndrome and had a serum C-reactive protein level of greater than 10 mg/dL. Patients were treated in the intensive care unit for more than 2 days. Patients were divided into two groups: survivors and non-survivors. We measured and compared eight kinds of fecal organic acids between the two groups. We focused on the minimum and maximum value of each fecal organic acid and evaluated prognostic factors by using classification and regression tree (CART) and multivariate logistic regression analyses. RESULTS: We included 90 patients as survivors and 38 as non-survivors. The CART analysis revealed that the dominant factors for mortality were the minimum values of propionate and acetate and the maximum values of lactate and formic acid. In the evaluation of the minimum values of fecal organic acids, propionate was significantly associated with increased mortality (odds ratio, 0.11 [95% confidence interval, 0.024-0.51]; P = 0.005), acetate (0.047 [0.005-0.49]; P = 0.01), and age (1.048 [1.015-1.083]; P = 0.004). In the evaluation of the maximum values, lactate was significantly associated with increased mortality (5.21 [2.024-13.42], P = 0.001) and age (1.050 [1.017-1.084]; P = 0.003). CONCLUSION: An altered balance of fecal organic acids was significantly associated with mortality in critically ill patients.

C1 Esterase Inhibitor Activity Is Reduced in the Acute Phase Following Burn Injury: A Prospective Observational Study.

Hereditary angioedema has been attributed to an inherited deficiency of C1 esterase inhibitor that increases vascular permeability. The role of C1 esterase inhibitor in burn patients has not been described previously. In this study, we attempted to identify the relationship between serial changes of C1 esterase inhibitor activity and the clinical course in major burn patients. This study was a single-center, prospective, observational study. C1 esterase inhibitor activity values were serially examined in major burn patients admitted into the burn center from April 2014 to December 2016. Inclusion criteria were age ≥16 years old and %TBSA burned ≥20%. This study included 38 patients with major burn. C1 esterase inhibitor activity after burn dropped acutely on days 1 and 2 but increased immediately until days 3 to 5, after which it continued to gradually increase to above the reference value. C1 esterase inhibitor activity on admission showed significant inverse correlation with the volume of infusion per body weight required in the first 24 hours after injury and %TBSA burned (r = -0.405, P = 0.01; r = -0.375, P = 0.02, respectively). C1 esterase inhibitor activity on admission was significantly lower in the nonsurvivors than in the survivors during the 28-day evaluation period (59% vs 90%, P = 0.01). These findings suggest that C1 esterase inhibitor may play a critical role in regulating vascular permeability in the acute phase following the burn injury.

Natural kinetics of blood cells following major burn: Impact of early decreases in white blood cells and platelets as prognostic markers of mortality.

BACKGROUND: Severely burned patients often suffer white blood cell and platelet drop following the injury. Though coagulopathy after burn injury have been reported, the association between leukopenia or thrombopenia and mortality is still unrevealed. To determine whether early drastic drops in white blood cells (WBCs) and platelets following injury can be prognostic markers in patients with major burns. METHODS: This is a retrospective cohort study setting in a single Burn Center in Japan. Data comprising patients' characteristics and blood cell counts (red blood cells [RBCs], WBCs including neutrophils, monocytes, and lymphocytes, and platelets) over the first 30 days after burn injury were serially collected from patients suffering major burn injury (≥20% TBSA) from January 1, 2006 to December 31, 2015. To determine blood cell counts affecting 60-day mortality, we used multivariable Cox proportional hazard analysis to assess associations between each blood cell count and mortality, adjusting for age and %TBSA as covariates, and evaluated predicted value of the hazard ratio (HR) of death. RESULTS: We enrolled 280 patients. Following burn injury, all blood cell counts were high at admission, then decreased. RBCs diminished progressively and plateaued 2 weeks after injury. WBCs decreased suddenly 2 days after injury, then increased and stabilized. Platelets decreased more rapidly than WBCs to their nadir at 3 days, then continually increased. After covariate adjustment, low RBCs from day 1 (HR: 0.566, 95% C.I. 0.423, 0.759) to day 5 (HR: 0.524, 95% C.I. 0.175, 0.576) were predictors of mortality. Neutrophil count was not a risk factor, but day 3 lymphocyte count (HR: 0.131, 95% C.I. 0.026, 0.646) and day 10 monocyte count (HR: 0.044, 95% C.I. 0.005, 0.396) were risk factors. Low platelet counts from day 3 (HR: 0.545, 95% C.I. 0.300, 0.981) to day 30 following injury were always a predictor of mortality. CONCLUSIONS: Early thrombopenia and lymphopenia were independent risk factors for 60-day mortality, and prolonged thrombopenia and monocytopenia were independent risk factors for mortality. These findings might shed light on mechanisms of immune response following severe burns.

Clinical Importance of a Cytokine Network in Major Burns.

Major burns elicit an acute inflammatory response including various inflammatory cytokines. Cytokines play mutual interacting roles in inflammatory diseases. There is little evidence of the clinical significance of the cytokine network in patients with major burns. This study aimed to investigate the clinical significance of the cytokine network in patients with major burn. This prospective observational study comprising 38 patients with major burns (total body surface area (%TBSA) ≥ 20%) and 12 healthy controls was conducted from April 2014 to December 2016. Blood samples were collected from patients at six points: day 1, day 2, days 3-5, 1 week, 2 weeks, and 1 month after the burn injury. Inflammatory cytokines (interferon [IFN]-α, IFN-γ, interleukin [IL]-1ß, IL-6, IL-8, IL-12/IL-23p40, IL-17A, monocyte chemotactic protein-1 [MCP-1], TNF-α), and anti-inflammatory cytokines (IL-4, IL-10) were measured. Twenty-eight-day mortality, %TBSA, prognostic burn index (PBI) and Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were evaluated. Hierarchical clustering analysis and network visualization showed one cluster and network, respectively. Both were formed by four cytokines including IL-6, IL-8, IL-10, and MCP-1 on days 1 and 2, suggesting the presence of a cytokine network in the early hospital phase. Each cytokine showed significant associations with the SOFA score within 5 days and 1 month after burn injury. Cox regression analysis highlighting days 1 and 2 showed significant correlation of IL-6, IL-8, and IL-10 with 28-day mortality. We showed a cytokine network and its relation with prognosis and injury severity on days 1 and 2 and suggest that this cytokine network may play a role in major burns.

Glycocalyx Shedding is Enhanced by Age and Correlates with Increased Fluid Requirement in Patients with Major Burns.

BACKGROUND: Massive fluid shift after severe burn injury leads to edema and intravascular fluid loss that may result in burn-induced compartment syndrome (BICS) when corrected by aggressive fluid resuscitation. Factors causing this fluid shift remain unclear. Because glycocalyx regulates endothelial permeability, we hypothesized that glycocalyx shedding would increase fluid requirements in burn patients. This prospective cohort study aimed to identify relationships between shedding of the glycocalyx and fluid requirements after burn injury. METHODS: Patients aged more than 18 years with burn injury over more than 20% total body surface area (TBSA) were enrolled. Patient background factors including age, sex, burn size, and inhalation injury were recorded at patient enrollment. Serum syndecan-1, known as a biomarker of glycocalyx shedding, was serially measured on admission, day 1, days 3 to 5, around 1 and 2 weeks, and 1 month after the injury to observe postburn injury kinetics of syndecan-1. As biomarkers of endothelial damage, soluble thrombomodulin, antithrombin III, and plasminogen activator inhibitor-1 were also measured. We determined the relationship between syndecan-1 and initial 24-h fluid requirements and between syndecan-1 and morbidity/mortality. RESULTS: We enrolled 39 patients (median age, 55 years; median burn size, 35%TBSA): 16 developed BICS, and 10 patients died. Syndecan-1 level on admission was significantly higher than that in healthy volunteers and remained so. Syndecan-1 level on admission was associated with patient age (ρ = 0.50, P = 0.001) but not burn size (ρ = 0.08, P = 0.63), and antithrombin III level on admission was negatively associated with burn size (ρ = -0.48, P = 0.002). The syndecan-1 level on admission was significantly associated with fluid requirement (mL/kg) (ρ = 0.38, P = 0.017). After adjustment for age, sex, %TBSA, and inhalation injury, syndecan-1 was an independent parameter for the increase in fluid requirement (P = 0.04) and development of BICS (P = 0.03) by multivariable regression analysis. These findings suggested that glycocalyx shedding increased in an age-dependent manner, whereas antithrombin III decreased according to burn size. CONCLUSIONS: Glycocalyx shedding occurs soon after burn injury in an age-dependent manner. To reduce fluid-related complications such as BICS, new strategies to protect glycocalyx in burn patients are needed.

Indications of early intubation for patients with inhalation injury.

Aim: For patients with inhalation injury, the indications for early intubation are diverse. The purpose of this study was to identify the most reliable symptoms, physical findings, and medical examinations with which to determine the indications for early intubation in patients with inhalation injury. Methods: We retrospectively collected patient data from medical records. Collected data included age, sex, burn size, symptoms, physical findings, carboxyhemoglobin levels (COHb), and bronchial wall thickness (BWT) determined from chest computed tomography images. We analyzed the relationships between these findings and the early intubation. We performed fiberoptic bronchoscopy in all patients, and analyzed the relationships between bronchoscopic severity and other findings. Results: Of the 205 patients, 80 patients were diagnosed as having inhalation injury, and 34 patients were intubated. Burn size, facial burns, neck burns, use of accessory respiratory muscles, and COHb seemed to be related with intubation, whereas singed nasal hair was not. If the patients suffered ≥27% total body surface area burn and BWT ≥3.5 mm, the positive predictive value for early intubation was 1.00. If the patients suffered smaller cutaneous burn without neck burn, and their COHb <4.0%, the negative predictive value for early intubation was 0.97. Fiberoptic bronchoscopy findings from above the glottis were mainly related with patients' symptoms. Findings from below the glottis were mainly related with BWT and COHb. Conclusions: Patients' symptoms, especially use of accessory respiratory muscles, are reliable, and BWT and COHb are also useful tools, for determining the indication for early intubation.

Acute intestinal damage following severe burn correlates with the development of multiple organ dysfunction syndrome: A prospective cohort study.

BACKGROUND: Severely burned patients occasionally suffer intestinal ischemia leading to a fatal outcome, and the gut is considered a "motor" driving the development of multiple organ failure. However, in clinical settings, it has been difficult to assess acute intestinal damage following burn and its consequence to patient outcome. Intestinal fatty acid binding protein (I-FABP) is a known biomarker for diagnosing intestinal ischemia/damage. This study aimed to assess the extent of intestinal damage using serial I-FABP measurements following severe burn and to clarify the association between intestinal damage and the development of organ dysfunctions. METHODS: Patients aged >15years old who suffered burn over 20% total body surface area (TBSA) were enrolled in this prospective cohort study. Patients with cardiac arrest on admission or who were transferred >24h after injury were excluded. Patients with chemical burn were also excluded. Burn size and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were recorded at the time of patient enrollment. I-FABP was measured on admission and at 1, 4, 7, 14, and 30days following injury. Other biomarkers such as lactate, lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase, amylase, and creatinine (Cre) were also measured at the same time points as I-FABP. We also evaluated the serial change in Sequential Organ Failure Assessment (SOFA) score. RESULTS: The study included 32 patients. Serum I-FABP level on the day of admission was significantly increased in the patients compared with healthy controls. Increased I-FABP levels were normalized at 4days after injury. The serum level of I-FABP on the day of admission correlated with %TBSA (III) and APACHE II score. A high I-FABP level on admission was associated with the subsequent development of multiple organ dysfunction. The increase in I-FABP level also correlated with increases of AST, LDH, and CK levels. CONCLUSIONS: Serum level of I-FABP on admission day does not correlate with burn size, but with the deep burn area. The gut might be a crucial target organ following severe burn, and gut damage could have an important role in the development of multiple organ dysfunction.