Background: Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression. Methods: Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture. Results: DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis. Conclusion Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

Purpose: A trauma center project for treating patients with trauma has been established in Korea. A trauma team is activated based on the Centers for Disease Control and Prevention (CDC) field triage Step 1 for patient triage. Here, we determined if the currently applied criteria were appropriate for the triage of patients with trauma in Korea. Methods: This retrospective study included patients who were taken to the regional trauma center from January 1, 2016 to December 31, 2019, and were registered in the Korean Trauma database. The rates for undertriage and overtriage were calculated from the in-field and in-hospital triage according to the CDC guidelines Step 1. Results: Among the 9,383 patients transferred to the trauma center, 3,423 were directly transferred from the site and were investigated. The overall rates for undertriage and overtriage of these patients were 28.13% and 30.35%, respectively. For the patients who received in-field triage and were directly transferred to the trauma center, the rates for undertriage and overtriage were 27.92% and 32.39%, and 25.92% and 29.11% for in-hospital triage, respectively. The concordance rate of triage was 87.09%. Conclusion The current use of in-hospital triage physiological criteria as set out in the CDC guidelines Step 1, indicated an undertriage rate which was high and an overtriage rate within the acceptable range. Further studies on triaging patients with trauma are warranted. Improvements in the guidelines of the trauma center project are necessary and this needs to be supported by resources and training for field personnel.

Purpose: The association of the initial serum ammonia level with in-hospital mortality in patients with acute glufosinate-ammonium herbicide poisoning was studied. Methods: This retrospective cohort study was conducted between March 2012 and August 2019 in the emergency department after glufosinate-ammonium herbicide poisoning. Survivors and non-survivors were analyzed using a Mann-Whitney U test and Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for mortality. Results: One hundred and six patients were enrolled; 11 died, yielding a mortality of 10.4%. The serum bicarbonate level was significantly lower in the non-survival group than the survival group. Age, serum ammonia, blood urea nitrogen, creatinine levels, SOFA score, and APACHE II score were significantly higher in the non-survival group than the survival group. Age, serum ammonia, and creatinine level were independent risk factors for mortality in multivariate logistic regression analysis. Conclusion The initial serum ammonia level is associated with mortality in patients with acute glufosinate herbicide poisoning.

Purpose: The association of the initial serum ammonia level with in-hospital mortality in patients with acute glufosinate-ammonium herbicide poisoning was studied. Methods: This retrospective cohort study was conducted between March 2012 and August 2019 in the emergency department after glufosinate-ammonium herbicide poisoning. Survivors and non-survivors were analyzed using a Mann-Whitney U test and Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for mortality. Results: One hundred and six patients were enrolled; 11 died, yielding a mortality of 10.4%. The serum bicarbonate level was significantly lower in the non-survival group than the survival group. Age, serum ammonia, blood urea nitrogen, creatinine levels, SOFA score, and APACHE II score were significantly higher in the non-survival group than the survival group. Age, serum ammonia, and creatinine level were independent risk factors for mortality in multivariate logistic regression analysis. Conclusion The initial serum ammonia level is associated with mortality in patients with acute glufosinate herbicide poisoning.

PURPOSE: Recently, the prevalence of allergic rhinitis (AR) in Korean children has been increased. The aim of this study was to investigate the clinical characteristics of rhinitis and to compare clinical parameters between AR and nonallergic rhinitis (NAR) in children.METHODS: We retrospectively reviewed the medical records of 1,034 children under 18 years of age who visited Korea University Anam Hospital for rhinitis symptoms from January 2008 to December 2017. Clinical data, including clinical features, comorbidities, blood test results, allergen sensitization profile, and pulmonary function test parameters, were collected.RESULTS: Among the 1,034 children with rhinitis, 737 (71.3%) were AR and 297 (28.7%) were NAR. The prevalence of AR gradually increased with age. The median levels of eosinophil count (4.1%), serum total IgE (204.4 IU/L), eosinophil cationic protein (ECP) concentration (17.9 µg/L), and fractional exhaled nitric oxide (FeNO) (22.0 ppb) were significantly higher in children with AR than in those with NAR. The sensitization rate to the inhalant allergens increased with age; however, food allergen sensitization rate tended to decrease. Median levels of eosinophil count, total IgE, ECP, and FeNO were significantly higher in the poly-sensitized group than in the mono-sensitized and nonsensitized groups.CONCLUSION: More than 70% of Korean children who have rhinitis symptoms are AR. Children with AR more likely to have higher levels of FeNO and bronchial asthma. Poly-sensitized children showed increased rates of atopic dermatitis and bronchial asthma.
Allergens ; Asthma ; Child ; Comorbidity ; Dermatitis, Atopic ; Eosinophil Cationic Protein ; Eosinophils ; Hematologic Tests ; Humans ; Immunoglobulin E ; Korea ; Medical Records ; Nitric Oxide ; Prevalence ; Respiratory Function Tests ; Retrospective Studies ; Rhinitis ; Rhinitis, Allergic

Background: Non-alcoholic fatty liver disease fibrosis score (NFS) is a scoring system applied in clinical practice to predict advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Evidence shows that progression of steatohepatitis and liver fibrosis reduces the production of verylow- density lipoprotein. The aim of this study was to identify the association of NFS and serum low-density lipoprotein cholesterol (LDL-C) levels and in adults with NAFLD. Methods: Data were gathered from 24,889 subjects who had visited a health promotion center. NFS was calculated to assess the severity of fibrosis in all the subjects. Serum LDL-C levels were measured using a direct method. Results: Serum LDL-C levels tended to decrease with increasing NFS quartiles (P for trend<0.01). NFS was one of the major determinants of serum LDL-C level after adjusting for age, sex, lifestyle-related factors, and other covariates. The estimated mean serum LDL-C level was significantly lower in the highest quartile of NFS than in the lowest quartile of NFS. Conclusion NFS had a negative association with serum LDL-C levels in adults with NAFLD. Elevated LDL-C level is not only a risk factor of cardiovascular disease but also a predictive indicator of NAFLD severity.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Purpose: Many studies have shown that the enhanced recovery after surgery (ERAS) protocols improve postoperative surgical outcomes. The purpose of this study was to observe the effects on postoperative inflammatory markers and to explore the effects of a high degree of compliance and the use of epidural anesthesia on inflammation and surgical outcomes. Methods: Four hundred patients underwent colorectal cancer surgery at 2 hospitals during 2 different periods, namely, from January 2006 to December 2009 and from January 2017 to July 2017. Data related to the patient’s clinicopathological features, inflammatory markers, percentage of compliance with elements of the ERAS protocol, and use of epidural anesthesia were collected from a prospectively maintained database. Results: The complication rate and the length of hospital stay (LOS) were less in the ERAS group than in the conventional group (P = 0.005 and P ≤ 0.001, respectively). The postoperative white blood cell count and the duration required for leukocytes to normalize were reduced in patients following the ERAS protocol (P ≤ 0.001). Other inflammatory markers, such as lymphocyte count (P = 0.008), neutrophil/lymphocyte ratio (P = 0.032), and C-reactive protein level (P ≤ 0.001), were lower in the ERAS protocol group. High compliance ( ≥ 70%) was strongly associated with the complication rate and the LOS (P = 0.008 and P ≤ 0.001, respectively). Conclusion ERAS protocols decrease early postoperative inflammation and improves short-term postoperative recovery outcomes such as complication rate and the LOS. High compliance ( ≥ 70%) with the ERAS protocol elements accelerates the positive effects of ERAS on surgical outcomes; however, the effect on inflammation was very small.

BACKGROUND: Early detection of vascular change may improve prediction of subclinical stage of cardiovascular disease, allowing intervention to prevent overt vascular damage. High heart rate is known to increase cardiovascular morbidity and mortality rate in the general population and in individuals with cardiovascular disease. We aimed to investigate the association between resting heart rate (RHR) measured using electrocardiogram (ECG) and arterial stiffness measured using the cardio-ankle vascular index (CAVI) in men. METHODS: Data were collected from 5,629 men aged between 20 and 78 years who visited a single-site health promotion center. RHR was measured in a supine posture after resting for 10 minutes using an ECG. Arterial stiffness was measured using the CAVI. The cutoff value for high CAVI was ≥9.0. RESULTS: RHR was one of the major determinants of high CAVI after adjusting for age, waist circumference, mean arterial pressure, glycosylated hemoglobin level, triglyceride level, white blood cell count, and lifestyle factors. When RHR groups were defined according to the RHR quartiles, the odds ratio of group with RHR ≥70 bpm, for high CAVI was 3.62 (95% confidence interval [CI], 2.21–5.91) after adjusting for age and lifestyle factors. This association was not changed after adjusting for all other covariates (odds ratio, 2.39; 95% CI, 1.36–4.19). CONCLUSIONS RHR measured using ECG is significantly associated with arterial stiffness in men not taking medications for hypertension, dyslipidemia, or diabetes. These findings suggest that RHR may be useful in assessing cardiovascular risk in men.