Deciphering AKI in Burn Patients: Correlations between Clinical Clusters and Biomarkers.

Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher (p < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.

Suspicious findings observed retrospectively on CT imaging performed before the diagnosis of pancreatic cancer.

Background: Few studies have focused on computed tomography findings before a pancreatic cancer diagnosis. We aimed to investigate the prediagnostic computed tomography findings of patients who had undergone computed tomography within the prediagnostic period of their pancreatic cancer diagnosis. Methods: Between January 2008 and December 2019, 27 patients who underwent contrast-enhanced abdominal or chest computed tomography including the pancreas within 1 year of a pancreatic cancer diagnosis were enrolled in this retrospective study. The prediagnostic computed tomography imaging findings were divided into pancreatic parenchyma and pancreatic duct findings. Results: All patients underwent computed tomography for reasons unrelated to pancreatic cancer. The pancreatic parenchyma and ducts showed normal findings in seven patients and abnormal findings in 20 patients. Hypoattenuating mass-like lesions were detected in nine patients with a median size of 1.2 cm. Six patients had focal pancreatic duct dilatations, and two patients had distal parenchymal atrophy. In three patients, two of these findings were found simultaneously. Taken together, 14 (51.9%) of 27 patients had findings suggestive of pancreatic cancer in prediagnostic computed tomography. Conclusions: In contrast-enhanced computed tomography performed for other purposes, attention should be paid to the presence of a hypoattenuating mass, focal pancreatic duct dilatation, or distal parenchymal atrophy of the pancreas. These features may be clues for an early diagnosis of pancreatic cancer.

YAP antagonizes TEAD-mediated AR signaling and prostate cancer growth.

Hippo signaling restricts tumor growth by inhibiting the oncogenic potential of YAP/TAZ-TEAD transcriptional complex. Here, we uncover a context-dependent tumor suppressor function of YAP in androgen receptor (AR) positive prostate cancer (PCa) and show that YAP impedes AR+ PCa growth by antagonizing TEAD-mediated AR signaling. TEAD forms a complex with AR to enhance its promoter/enhancer occupancy and transcriptional activity. YAP and AR compete for TEAD binding and consequently, elevated YAP in the nucleus disrupts AR-TEAD interaction and prevents TEAD from promoting AR signaling. Pharmacological inhibition of MST1/2 or LATS1/2, or transgenic activation of YAP suppressed the growth of PCa expressing therapy resistant AR splicing variants. Our study uncovers an unanticipated crosstalk between Hippo and AR signaling pathways, reveals an antagonistic relationship between YAP and TEAD in AR+ PCa, and suggests that targeting the Hippo signaling pathway may provide a therapeutical opportunity to treat PCa driven by therapy resistant AR variants.

YAP inhibits ERα and ER+ breast cancer growth by disrupting a TEAD-ERα signaling axis.

Hippo signaling restricts tissue growth by inhibiting the transcriptional effector YAP. Here we uncover a role of Hippo signaling and a tumor suppressor function of YAP in estrogen receptor positive (ER+) breast cancer. We find that inhibition of Hippo/MST1/2 or activation of YAP blocks the ERα transcriptional program and ER+ breast cancer growth. Mechanistically, the Hippo pathway transcription factor TEAD physically interacts with ERα to increase its promoter/enhancer occupancy whereas YAP inhibits ERα/TEAD interaction, decreases ERα occupancy on its target promoters/enhancers, and promotes ERα degradation by the proteasome. Furthermore, YAP inhibits hormone-independent transcription of ERα gene (ESR1). Consistently, high levels of YAP correlate with good prognosis of ER+ breast cancer patients. Finally, we find that pharmacological inhibition of Hippo/MST1/2 impeded tumor growth driven by hormone therapy resistant ERα mutants, suggesting that targeting the Hippo-YAP-TEAD signaling axis could be a potential therapeutical strategy to overcome endocrine therapy resistance conferred by ERα mutants.

Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View.

Initially identified in Drosophila, the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Many upstream signals, including cell adhesion, polarity, mechanical stress, and soluble factors, regulate Hippo signaling through the kinase cascade, leading to change in the cytoplasmic/nuclear localization of Yki/YAP/Taz. However, recent studies have uncovered other mechanisms that regulate Yki/YAP/Taz subcellular localization, stability, and activity independent of the Hpo kinase cascade. These mechanisms provide additional layers of pathway regulation, nodes for pathway crosstalk, and opportunities for pathway intervention in cancer treatment and regenerative medicine.

CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus.

Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer.

A clinical trial with a novel collagen dermal substitute for wound healing in burn patients.

Human skin incurs damage in various ways; a few of the recognizable factors are electric burns, chemical burns, scalding burns, surgery, and physical injuries, such as automobile accidents. If skin damage is extensive and severe enough [second degree and total body surface area (TBSA) involvement of >20%], the skin will lose the ability to regenerate itself. Burn wounds are treated in various ways. For full-thickness skin defects, the mainstay of treatment is an autologous split-thickness skin graft. However, there are some limitations due to scars, poor elasticity, and limitations in the joint movements due to contractures. Recently, artificial dermis has been widely used to minimize contractures. The use of dermal replacements for the treatment of burns brings new hope in maintaining the characteristics of the normal dermis. Herein, Insuregraf® was used for skin regeneration in patients who had burn injury from flames, electricity, heat, or steam. The mean take-rate values at 7 and 14 days after operation were 94.55 ± 3.02% and 97.40 ± 2.57%, respectively. Furthermore, areas covered by Insuregraf® showed higher mean values of trans-epidermal water loss (24.6 ± 3.9 g h-1 m-2), gross elasticity (Ua/Uf = 0.76 ± 0.24), and biological elasticity (Ur/Uf = 0.55 ± 0.1). These values were much better than those of the control where Insuregraf® was not used (p = 0.030, p = 0.040, and p = 0.013, respectively). Furthermore, the biomechanical scar properties of Insuregraf® and Matriderm were very similar. Hence, we suggest that Insuregraf® can be used in the medical field.

Phosphorylation of Ci/Gli by Fused Family Kinases Promotes Hedgehog Signaling.

Hedgehog (Hh) signaling culminates in the conversion of the latent transcription factor Cubitus interruptus (Ci)/Gli into its activator form (CiA/GliA), but the underlying mechanism remains poorly understood. Here, we demonstrate that Hh stimulates the phosphorylation of Ci by the Ser/Thr kinase Fused (Fu) and that Fu-mediated phosphorylation of Ci promotes its activation. We find that Fu directly phosphorylates Ci on Ser218 and Ser1230, which primes its further phosphorylation by CK1 on adjacent sties. These phosphorylation events alter Ci binding to the pathway inhibitor Suppressor of fused (Sufu) and facilitate the recruitment of Transportion and the transcriptional coactivator CBP. Furthermore, we provide evidence that Sonic hedgehog (Shh) activates Gli2 by stimulating its phosphorylation on conserved sites through the Fu-family kinases ULK3 and mFu/STK36 in a manner depending on Gli2 ciliary localization. Hence, Fu-family kinase-mediated phosphorylation of Ci/Gli serves as a conserved mechanism that activates the Hh pathway transcription factor.

Hippo signaling is intrinsically regulated during cell cycle progression by APC/CCdh1.

The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/CCdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

Pulmonary Extraintestinal Manifestation of Crohn's Disease Treated Successfully with Adalimumab.

Pulmonary extraintestinal manifestation is rare in Crohn's disease and has been reported in only a few cases. Despite the presence of pulmonary abnormalities in a significant proportion of patients with inflammatory bowel disease, there are only few case reports, due to complicated diagnosis and low recognition by clinicians. Currently, treatment guidelines for pulmonary Crohn's disease have not been established. There are some case reports of pulmonary Crohn's disease that achieved remission after infliximab treatment. Clinical and radiological remission of pulmonary extraintestinal involvement in Crohn's disease after adalimumab therapy has not been reported yet. Here, we report one case of lung involvement of Crohn's disease, which shows radiological and clinical remission after adalimumab treatment.

Diagnostic performance of plasma and urine neutrophil gelatinase-associated lipocalin, cystatin C, and creatinine for acute kidney injury in burn patients: A prospective cohort study.

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.

Regulation of Yki/Yap subcellular localization and Hpo signaling by a nuclear kinase PRP4K.

Hippo (Hpo) signaling pathway controls tissue growth by regulating the subcellular localization of Yorkie (Yki)/Yap via a cytoplasmic kinase cassette containing an upstream kinase Hpo/MST1/2 and a downstream kinase Warts (Wts)/Lats1/2. Here we show that PRP4K, a kinase involved in mRNA splicing, phosphorylates Yki/Yap in the nucleus to prevent its nuclear accumulation and restrict Hpo pathway target gene expression. PRP4K inactivation accelerates whereas excessive PRP4K inhibits Yki-driven tissue overgrowth. PRP4K phosphorylates a subset of Wts/Lats1/2 sites on Yki/Yap to inhibit the binding of Yki/Yap to the Scalloped (Sd)/TEAD transcription factor and exclude Yki/Yap nuclear localization depending on nuclear export. Furthermore, PRP4K inhibits proliferation and invasiveness of cultured breast cancer cells and its high expression correlates with good prognosis in breast cancer patients. Our study unravels an unanticipated layer of Hpo pathway regulation and suggests that PRP4K-mediated Yki/Yap phosphorylation in the nucleus provides a fail-safe mechanism to restrict aberrant pathway activation.

Safety and Effectiveness of Endoscopist-Directed Nurse-Administered Sedation during Gastric Endoscopic Submucosal Dissection.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is routinely performed in treating gastric neoplasia and requires long-term higher levels of sedation. Endoscopist-directed nurse-administered sedation (EDNAS) has not been well studied in ESD. This study aimed to evaluate the safety and effectiveness of EDNAS for ESD. METHODS: Patients treated with ESD for gastric tumors between 2013 and 2015 were retrospectively collected. Patients were divided into a midazolam-treated group (M group) and a midazolam plus propofol-treated group (MP group). Clinical outcome, safety, effectiveness, adverse events of ESD, and adverse events of sedation were analyzed. RESULTS: Of 209 collected patients, 83 were in the M group and 126 were in the MP group. Of all patients, 67 patients had the circulatory adverse event during the ESD procedure. Sedation method was the only significant risk factor (M versus MP: 2.17 (1.14-4.15), p = 0.019). In analysis of MP subgroups, 47 patients suffered an adverse event from sedation, and current smoking was the only significant association factor for adverse event (0.15 (0.03-0.68), p = 0.014). CONCLUSIONS: In performing ESD, the effect of sedation is reduced in smoking patients. EDNAS may be acceptable for ESD under careful monitoring of vital sign and oxygen saturation.

Evaluation of diagnostic biomarkers for acute kidney injury in major burn patients.

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.

Serum cystatin C and microalbuminuria in burn patients with acute kidney injury.

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 < 0.001) at postburn day 7 and 0.908 (95% CI, 0.843-0.973, P < 0.001) at postburn day 14. The results were 0.610 (95% CI, 0.497-0.724, P = 0.069) for ACR at postburn day 7 and 0.694 (95% CI, 0.589-0.798, P = 0.001) at postburn day 14. The optimal cut-off value of serum cystatin C at postburn day 14 and ACR at postburn day 14 were 0.85 mg/L (sensitivity, 89.5%; specificity, 82.5%) and 41.51 mg/g cre (sensitivity, 60.5%; specificity, 61.4%), respectively. Serum cystatin C at postburn day 14 was the only significant factor in relation to AKI. CONCLUSIONS: Serum cystatin C is a valuable diagnostic marker, whereas microalbuminuria is a relatively less significant marker for AKI in major burn patients.

The application of cultured epithelial autografts improves survival in burns.

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.

Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling.

The Hippo (Hpo) tumor suppressor pathway is an evolutionarily conserved signaling pathway that controls tissue growth and organ size in species ranging from Drosophila to human, and its malfunction has been implicated in many types of human cancer. In this study, we conducted a kinome screen and identified Happyhour (Hppy)/MAP4K3 as a novel player in the Hpo pathway. Our biochemical study showed that Hppy binds and phosphorylates Wts. Our genetic experiments suggest that Hppy acts in parallel and partial redundantly with Misshapen (Msn)/MAP4K4 to regulate Yki nuclear localization and Hpo target gene expression in Drosophila wing imaginal discs. Furthermore, we showed that cytoskeleton stress restricts Yki nuclear localization through Hppy and Msn when Hpo activity is compromised, thus providing an explanation for the Wts-dependent but Hpo-independent regulation of Yki in certain contexts. Our study has unraveled an additional layer of complexity in the Hpo signaling pathway and laid down a foundation for exploring how different upstream regulators feed into the core Hpo pathway.

Inhalation injury in burn patients: establishing the link between diagnosis and prognosis.

This study was to re-evaluate inhalation injury as a prognostic factor in burn patients and to determine the factors that should be considered when refining the definition of inhalation injury. A total of 192 burn patients (152 men, 40 women; mean age, 46.1±13.8 years) who were suspected to have an inhalation injury and underwent bronchoscopy between January 2010 and June 2012 were included in this prospective observational study. All patients underwent bronchoscopy within 24h of sustaining the burn. The bronchoscopic findings were classified as normal, mild, moderate, and severe. Mechanical ventilation was administered, when required. Age, percentage of TBSA burned, ABSI score, requirement of mechanical ventilation and PF ratio, but not inhalation injury, COHb level, and bronchoscopic grades, significantly differed between the survivors and non-survivors (p<0.05). Mechanical ventilation (adjusted odds ratio [OR]: 9.787) and severe inhalation injury on bronchoscopy (adjusted OR: 45.357) were independent predictors of mortality on multivariate logistic regression analysis. Inhalation injury diagnosed through history does not predict mortality from burns. Other components such as severity of inhalation injury determined using bronchoscopy, and administration of mechanical ventilation might help predict the morbidity and mortality of burn patients with inhalation injury and all of the factors should be considered when the definition of inhalation injury is refined.

Assessment of biochemical markers in the early post-burn period for predicting acute kidney injury and mortality in patients with major burn injury: comparison of serum creatinine, serum cystatin-C, plasma and urine neutrophil gelatinase-associated lipocalin.

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.