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Background/aims: The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time., Methods: This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran- Armitage trend test., Results: Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028)., Conclusion: Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

Background: Nonpharmacological interventions (NPIs) reduce the incidence of respiratory infections. After NPIs imposed during the coronavirus disease 2019 pandemic ceased, respiratory infections gradually increased worldwide. However, few studies have been conducted on severe respiratory infections requiring hospitalization in pediatric patients. This study compares epidemiological changes in severe respiratory infections during pre-NPI, NPI, and post-NPI periods in order to evaluate the effect of that NPI on severe respiratory infections in children., Methods: We retrospectively studied data collected at 13 Korean sentinel sites from January 2018 to October 2022 that were lodged in the national Severe Acute Respiratory Infections (SARIs) surveillance database., Results: A total of 9,631 pediatric patients were admitted with SARIs during the pre-NPI period, 579 during the NPI period, and 1,580 during the post-NPI period. During the NPI period, the number of pediatric patients hospitalized with severe respiratory infections decreased dramatically, thus from 72.1 per 1,000 to 6.6 per 1,000. However, after NPIs ceased, the number increased to 22.8 per 1,000. During the post-NPI period, the positive test rate increased to the level noted before the pandemic., Conclusion: Strict NPIs including school and daycare center closures effectively reduced severe respiratory infections requiring hospitalization of children. However, childcare was severely compromised. To prepare for future respiratory infections, there is a need to develop a social consensus on NPIs that are appropriate for children., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background/aims: Chronic hepatitis C (CHC) is the second leading cause of liver-related mortality and is more prevalent in the elderly population in Korea. Decisions to initiate treatment and selection of proper antiviral agents may be challenging among elderly patients due to relevant comorbidities, comedications, and drug-drug interaction (DDI). It may be helpful to understand the current demographic status and comorbidities of CHC patients in the country., Methods: Patients aged ≥ 18 years and diagnosed with CHC (KCD-7 code B18.2) were extracted from the Korean Health Insurance Review & Assessment Service database in 2018. Data on comorbidities and comedications were assessed and potential DDIs were analyzed., Results: A total of 50,476 patients with CHC, with a mean age of 60.3 years and 46.7% male patients were identified. The proportion of patients with cirrhosis, hepatocellular carcinoma, and liver transplantation was 6.0%, 4.1%, and 0.3%, respectively and 37.2% of patients were more than 65 years of age. The three most common comorbidities were diseases of the digestive system (83.7%), respiratory system (58.2%), and musculoskeletal system and connective tissue (57.6%). The three most common comedications were analgesics (91.6%), gastrointestinal agents (85%), and antibacterials (80.3%). Lipid-lowering agents and anticonvulsants were prescribed in 28.5% and 14.8% of patients. Rate of potential DDI for contraindication was 2.2%, 13.1%, and 15.6% with sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir., Conclusion: With the increasing age of patients with CHC, comorbidity, comedication, and potential DDI should be considered when choosing antivirals in Korea. Sofosbuvir-based regimens showed favorable DDI profiles among Korean patients.

Background and Aims: Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia., Methods: We conducted a nationwide cohort study involving 4 031 948 subjects aged 40-69 years who underwent ≥2 health check-ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non-NAFLD (HSI <30 at all check-ups) and NAFLD (HSI >36 at one or more check-ups). Dementia defined by ICD-10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk., Results: At baseline, 31.3% had NAFLD. During the median follow-up of 9.5 years, 138 424 in NAFLD group and 69 982 in non-NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non-NAFLD group on multivariable-adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity-score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non-obese NAFLD subjects (BMI <25 kg/m 2 , HR, 1.09; p < .001) than obese NAFLD subjects., Conclusions: This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non-obese NAFLD subjects., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background & Aims: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk., Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development., Results: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up., Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir., Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance., Competing Interests: Conflict of interest Hwi Young Kim: Nothing to declare; Pietro Lampertico: Speaking bureau/advisor for AbbVie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma, Roche; Joon Yeul Nam: Nothing to declare; Hyung-Chul Lee: Nothing to declare; Seung Up Kim: Receiving grants from Yuhan Pharmaceuticals, and lecture fees from Bristol-Myers Squibb, Gilead Science and Yuhan Pharmaceuticals; Dong Hyun Sinn: Nothing to declare; Yeon Seok Seo: Nothing to declare; Han Ah Lee: Nothing to declare; Soo Young Park: Nothing to declare; Young-Suk Lim: Advisory board member of and receives research funding from Gilead Sciences; Eun Sun Jang: Nothing to declare; Eileen L. Yoon: Nothing to declare; Hyoung Su Kim: Nothing to declare; Sung Eun Kim: Nothing to declare; Sang Bong Ahn: Nothing to declare; Jae-Jun Shim: Nothing to declare; Soung Won Jeong: Nothing to declare; Yong Jin Jung: Nothing to declare; Joo Hyun Sohn: Nothing to declare; Yong Kyun Cho: Nothing to declare; Dae Won Jun: Nothing to declare; George N. Dalekos: Advisor/lecturer for AbbVie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Roche; grant support from Bristol-Myers Squibb, Gilead, Roche; Ramazan Idilman: Nothing to declare; Vana Sypsa: Advisor/lecturer for AbbVie, Gilead, Janssen; research grants from AbbVie, Gilead; Thomas Berg: Advisor/consultant/lecturer for AbbVie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex; Research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche; Maria Buti: Advisor/lecturer for AbbVie, Arbutus, Bristol-Myers Squibb, Gilead, Glaxo Smith-Kleine, Merck, Roche, Spring Bank; Jose Luis Calleja: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck; John Goulis: advisor/lecturer for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche; research grant from Bristol-Myers Squibb; Spilios Manolakopoulos: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche; grants from Bristol-Myers Squibb, Gilead; Harry LA Janssen: Consultant for and grants from AbbVie, Arbutus, Bristol Myers Squibb, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., Viroclinics; Myoung-jin Jang: Nothing to declare; Yun Bin Lee: Research grant from Samjin Pharmaceuticals and Yuhan Pharmaceuticals; Yoon Jun Kim: Research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals and Handok Pharmaceuticals; Jung-eHwan Yoon: Research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals and Daewoong Pharmaceuticals; Jeong-Hoon Lee: Lecture fees from GreenCross Cell, Daewoong Pharmaceuticals and Gilead Korea; George V. Papatheodoridis: Advisor/lecturer for AbbVie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, Spring Bank; research grants AbbVie, Gilead. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population., Methods: We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n = 1480, Korea prospective SAINT cohort) and the validation cohort (n = 426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine and random forest algorithms to develop the HCC prediction model and selected the most optimal method., Results: We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-foetoprotein and platelet at 12 months showed the best performance (AUROC = 0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC = 0.844) and better than other existing prediction models including the APA, PAGE-B and GAG models (AUROC = 0.769 to 0.818)., Conclusions: We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12 months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844) (Clinical trial number: KCT0003487)., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Subarachnoid hemorrhage is a potentially devastating cerebrovascular attack with a high proportion of poor outcomes and mortality. Recent studies have reported decreased mortality with the improvement in devices and techniques for treating ruptured aneurysms and neurocritical care. This study investigated the relationship between hospital volume and short- and long-term mortality in patients treated with subarachnoid hemorrhage., Methods: We selected subarachnoid hemorrhage patients treated with clipping and coiling from March-May 2013 to June-August 2014 using data from Acute Stroke Registry, and the selected subarachnoid hemorrhage (SAH) patients were tracked in connection with data of Health Insurance Review and Assessment Service to evaluate the short-term and long-term mortality., Results: A total of 625 subarachnoid hemorrhage patients were admitted to high-volume hospitals (n = 355, 57%) and low-volume hospitals (n = 270, 43%) for six months. The mortality of SAH patients treated with clipping and coiling was 12.3%, 20.2%, 21.4%, and 24.3% at 14 days, three months, one year, and five years, respectively. The short-term and long-term mortality in high-volume hospitals was significantly lower than that in low-volume hospitals. On Cox regression analysis of death in patients with severe clinical status, low-volume hospitals had significantly higher mortality than high-volume hospitals during short-term follow-up. On Cox regression analysis in the mild clinical status group, there was no statistical difference between high-volume hospitals and low-volume hospitals., Conclusion: In subarachnoid hemorrhage patients treated with clipping and coiling, low-volume hospitals had higher short-term mortality than high-volume hospitals. These results from a nationwide database imply that acute SAH should be treated by a skilled neurosurgeon with adequate facilities in a high-volume hospital., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: It is important to assess the prognosis of patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD (AECOPD). Recently, it was suggested that diffusing capacity of the lung for carbon monoxide (D LCO ) should be added to multidimensional tools for assessing COPD. This study aimed to compare the D LCO and forced expiratory volume in one second (FEV 1 ) to identify better prognostic factors for admitted patients with AECOPD., Methods: We retrospectively analyzed 342 patients with AECOPD receiving inpatient treatment. We classified 342 severe AECOPD patients by severity of D LCO and FEV 1 (≤ vs. > 50% predicted). We tested the association of FEV 1 and D LCO with the following outcomes: in-hospital mortality, need for mechanical ventilation, need for intensive care unit (ICU) care. We analyzed the prognostic factors by multivariate analysis using logistic regression. In addition, we conducted a correlation analysis and receiver operating characteristic (ROC) curve analysis., Results: In multivariate analyses, D LCO was associated with mortality (odds ratio = 4.408; 95% CI 1.070-18.167; P = 0.040) and need for mechanical ventilation (odds ratio = 2.855; 95% CI 1.216-6.704; P = 0.016) and ICU care (odds ratios = 2.685; 95% CI 1.290-5.590; P = 0.008). However, there was no statistically significant difference in mortality rate when using FEV 1 classification (P = 0.075). In multivariate linear regression analyses, D LCO (B = - 0.542 ± 0.121, P < 0.001) and FEV 1 (B = - 0.106 ± 0.106, P = 0.006) were negatively associated with length of hospital stay. In addition, D LCO showed better predictive ability than FEV 1 in ROC curve analysis. The area under the curve (AUC) of D LCO was greater than 0.68 for all prognostic factors, and in contrast, the AUC of FEV 1 was less than 0.68., Conclusion: D LCO was likely to be as good as or better prognostic marker than FEV 1 in severe AECOPD.

Background: Regular clinic follow-up is a prerequisite for optimal antiviral therapy and surveillance of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). However, adherence to regular follow-up stays low in practice. This study investigated whether regular follow-up is associated with decreased liver cancer mortality in CHB patients., Methods: A nationwide population-based historical cohort study was conducted using customized data from the National Health Insurance Service of Korea. The number of hospital visits every 3-month interval was counted for 2 years from the date of CHB diagnosis. Patients were classified into three follow-up groups: regular (four to eight visits), irregular (one to three visits), and no follow-up. The risk of liver cancer mortality was compared among the groups using Cox proportional hazard regression analysis., Results: Of the 414 074 CHB patients, 22.9% had regular follow-up. In multivariable analysis, regular follow-up was independently associated with decreased risk of liver cancer mortality compared to no follow-up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50-0.63, P < .001). Regular follow-up was also associated with the lowest risk of all-cause mortality (HR, 0.60; 95% CI, 0.57-0.63, P < .001). Patients with regular follow-up received more curative treatment (23.1% vs 15.1%, P < .001). Patients were less motivated when they were female, >60 years, of low socioeconomic status, disabled, lived in a rural area, had a higher comorbidity rate, or did not have cirrhosis., Conclusions: Regular follow-up at least every 3-6 months is significantly associated with reduced liver cancer mortality in patients with CHB., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Particulate matter (PM) is increasing every year in Asia. It is not fully understood how the airway is affected when inhaling PM. We investigated the correlation between particulate matter with a diameter of less than 10  μ m (PM 10 ) and fractional exhaled nitric oxide (FeNO) to determine whether PM causes airway inflammation. Material and Methods . We analyzed patients who visited our outpatient clinic and tested FeNO from January 2016 to December 2017 at the Korea University Guro Hospital. PM 10 data were provided by the government of the Republic of South Korea, and measuring station of PM 10 is located 800 meters from the hospital. We analyzed the correlation between PM 10 and FeNO by a Pearson correlation analysis and by a multivariate linear regression analysis. To identify the most correlated times, we analyzed the correlation between the FeNO and PM 10 daily average from the day of visit to 4 days before visit., Results: FeNO positively correlated with PM 10 at two days before hospital visit in the Pearson correlation (Pearson correlation coefficient = 0.057; P -value = 0.023) and in the multivariate linear regression analysis ( B  = 0.051, P -value = 0.026). If the PM 10 increased by 100  μ g/m 3 , the FeNO result was expected to rise to 8.3 ppb in healthy people without respiratory disease., Conclusion: The positive correlation was found in both healthy people and asthmatic patients. Therefore, PM 10 can increase airway inflammation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Juwhan Choi et al.)

Little is known about the benefits of statin use on liver cancer mortality among patients with chronic hepatitis B (CHB) considering hypercholesterolemia and obesity. A nationwide retrospective cohort study was conducted using data from a Health Examination Cohort of the National Health Insurance Service of Korea. Data on CHB patients with no other concurrent liver disease were acquired, and statin use was defined as a cumulative daily dose ≥28. A 3-year landmark analysis was performed to avoid immortal time bias. Patients who started statin therapy within the landmark date were considered statin users. A Cox regression analysis was applied to assess associations between statin use and liver cancer mortality considering hypercholesterolemia and obesity. Among 13063 patients, 193 (1.5%) died of liver cancer during the mean follow-up period of 10.6 years. After adjusting for demographic and metabolic factors, statin use [hazard ratio (HR), 0.17; 95% confidence interval (CI), 0.04-0.70] and hypercholesterolemia (HR, 0.46; 95% CI, 0.24-0.88 for total cholesterol ≥240 mg/dL) were associated with a decreased risk of liver cancer mortality, whereas body mass index (BMI) ≥30 kg/m² was associated with an increased risk of liver cancer mortality (HR, 2.46; 95% CI, 1.20-5.06). This study showed that statin use was associated with decreased liver cancer mortality when adjusting for cholesterol levels and BMI. This study found that hypercholesterolemia was independently associated with decreased liver cancer mortality regardless of statin use., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Background: Elevation of serum ferritin levels is frequently observed in non-alcoholic fatty liver disease (NAFLD) patients. Our study aims to examine the association between serum ferritin levels and NAFLD in Korean population., Methods and Results: A total of 25,597 participants were selected from Korean National Health and Nutritional Examination Surveys 2007-2012. The NAFLD liver fat score (NLFS) was used to define NAFLD. Elevation of ALT levels was defined as ALT level > 40 IU/L for male and ALT level > 31 IU/L for female. Multiple logistic regression was used to examine the association of serum ferritin levels and NAFLD by sex. After adjusting for multiple covariates, the ORs (95% CI) of the elevated ALT levels were 1.56 (95% CI: 1.17-2.07), 1.84 (95% CI: 1.39-2.45), and 4.08 (95% CI: 3.08-5.40) for the second, third and fourth serum ferritin quartiles in male (p for trend < 0.01), 1.67 (95% CI: 1.24-2.23), 2.23 (95% CI: 1.68-2.96), and 5.72 (95% CI: 4.32-7.60) for the second, third and fourth serum ferritin quartiles in female (p for trend < 0.01). Serum ferritin levels were also significantly associated with NAFLD and liver fibrosis both in male and female., Conclusions: Elevation of serum ferritin level is significantly associated with NAFLD and blood ALT elevation in Korean general population.

Purpose: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea., Materials and Methods: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation., Results: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identification, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease ( p =0.020 overall, p =0.011 for P. aeruginosa , p =0.048 for S. pneumoniae ). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group ( p =0.003 for S. aureus , p =0.009 for K. pneumoniae ). All viruses were seasonal (i.e., greater prevalence in a particular season; p <0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring., Conclusion: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD., Patients and Methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD., Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV 1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV 1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P <0.001)., Conclusion: Patients with T-COPD have higher levels of inflammatory markers, and IL-6 has a predictive value for AE in T-COPD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified., Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission., Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa ( P =0.003 and P =0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate ( P =0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification ( P =0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296-17.041; P =0.019)., Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear., Methods: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years., Results: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women., Conclusions: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Combined pulmonary fibrosis and emphysema (CPFE) patients visit hospitals frequently due to acute exacerbations (AEs); however, the predictors of CPFE AE have not been comprehensively described in literature. Thus, we investigated the predicting factors of AE in CPFE patients.We retrospectively reviewed medical records from the past 12 years at Korea University Guro Hospital. We selected CPFE patients by computed tomography findings. Rapid deterioration (RD) was defined as acute worsening of dyspnea requiring hospitalization and the presence of newly developed radiologic abnormalities. AE was defined as RD with newly acquired bilateral pulmonary infiltrates without evidence of pulmonary infection or other known causes. We evaluated the following variables in CPFE patients: age, sex, smoking history and amount, body mass index, past medical history, pulmonary function test, gender, age, and physiology (GAP) score, and the presence of lung cancer.Among 227 CPFE patients, 108 had RD and 31 developed AE. The most common cause of RD was infection (n = 60, 55.6%) and 28.7% (n = 31) developed AE. Lung cancer [hazard ratio (HR), 3.274; 95% confidence interval (95% CI) 1.444-7.425; P < .01] and GAP score (HR, 1.434; 95% CI 1.072-1.918; P = .02) were significant predictors of AE. The presence of lung cancer and AE were significant predictors of mortality.In conclusion, CPFE patients with lung cancer and high GAP scores should be carefully observed for AE.

Purpose: Asthma-COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of l-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition., Patients and Methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary l-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups., Results: Urinary l-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary l-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary l-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm -3 ; and frequent exacerbations ( P < 0.05)., Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population., Methods: We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay., Results: MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC., Conclusions: We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population.

Purpose: Increased awareness and understanding of chronic obstructive pulmonary disease (COPD) is an important aspect of disease management. The aim of this study was to explore COPD awareness among smokers participating in a smoking cessation program., Materials and Methods: Face-to-face interviews were conducted with 289 subjects in three smoking cessation clinics, using a structured questionnaire., Results: A total of 68.2% of subjects had COPD-related symptoms, and 19.7% were in poor health. Only 1.0% of the subjects knew that COPD was a respiratory disease. A total of 2.4% of subjects had been diagnosed with COPD and received treatment. Television was the most common source of information about COPD, with 57.1% of the subjects receiving information in this way. After being informed about COPD, smoking-cessation willingness increased in 84.1% of the study group. It increased in 86.3% of the subjects without awareness of COPD and in 81.2% of subjects with COPD-related symptoms., Conclusion: We found that awareness of COPD is very poor among current smokers in Korea. Many smokers perceived their health status as good, despite the presence of COPD-related symptoms. As the level of smoking-cessation willingness was different between those with and without awareness of COPD or COPD-related symptoms, a personalized education program with various educational tools may be needed to enhance awareness of the disease and to motivate smokers to quit.

Background/aims: Cigarette smoking is the most common risk factor for chronic obstructive pulmonary disease (COPD). However, few studies of the attitudes toward COPD of smokers, the group at risk of developing this condition, have been conducted. The purpose of this study was to explore the awareness of and attitudes toward COPD of current smokers., Methods: The sample consisted of 502 individuals aged 45 and older from throughout Korea who smoked at least 10 packs of cigarettes per year. Telephone interviews using a structured questionnaire were conducted with respondents., Results: First, we evaluated the health status of subjects, finding that 45.4% considered themselves to be in good health. We also asked about COPD-related symptoms, and 60.6% of subjects reported such symptoms. However, only 1.2% of subjects had been diagnosed with or treated for COPD, only 0.4% spontaneously mentioned COPD as a respiratory disease, and only 26.5% recognized COPD as a respiratory disease after seeing a list of such diseases. Television ranked as the top source of information about COPD. The willingness of 45.0% of subjects to stop smoking increased after being informed about COPD., Conclusions: Despite having COPD-related symptoms, most smokers did not know that COPD is a respiratory disease. The attitudes of smokers toward COPD and smoking cessation varied according to socioeconomic status. In summary, a continuous effort to increase the awareness of COPD among smokers is needed. Additionally, strategies tailored according to different socioeconomic groups will also be necessary.

Goals: The goal of the study was to investigate the current prevalence and causes of elevated alanine transaminase (ALT) in the general Korean population., Background: Incidentally elevated ALT is frequently found because of increasing access to hospitals and blood tests., Study: A population-based cross-sectional study was carried out based on the Fourth Korean National Health and Nutrition Examination Survey (K-NHANES). Eligible subjects included 7894 men and 10,197 women. We defined elevated ALT as >43 U/L. Among the subjects with elevated ALT, those who consumed alcohol, had the hepatitis B surface antigen (HBsAg), were obese (body mass index ≥25 kg/m), were insulin resistant (the homeostasis model assessment-insulin resistance), or had metabolic syndrome (MetS) were investigated., Results: The prevalence of elevated ALT was 7.4% in the Korean population. Increased ALT was more common in men (11.6%) than in women (3.1%) (P<0.001). Subjects with hypertension, diabetes, dyslipidemia (cholesterol ≥240 mg/dL or triglycerides ≥150 mg/dL), obesity, significant consumption of alcohol, HBsAg positive, or MetS were associated with elevated ALT (all P<0.001). The most common potential cause of elevated ALT was metabolic disorder (MetS, obesity, and/or insulin resistance), which comprised 74.9% of cases. MetS was found in 42.7% of men and 49.7% of women (P=0.031). Excess alcohol drinking was found in 29.6% of men and 7.5% of women with elevated ALT (P<0.001). HBsAg positivity was found in only 6% of subjects., Conclusions: Incidentally elevated ALT is common in the Korean population. It is associated with metabolic disorders (obesity, insulin resistance, or MetS) in the majority of patients. This finding suggests that nonalcoholic fatty liver disease might be the most common cause of elevated ALT in the general Korean population.

Background/aims: This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis., Methods: Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals., Results: Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9 ± 30.2 months (mean ± SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality., Conclusions: A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.

Background/aim: The standard treatment for patients with gastric low-grade dysplasia (LGD) remains controversial, even though diagnosis of LGD is increasingly common as esophagogastrodeuodenoscopy becomes more available. The aim of this study was to identify a lesion size cut-off as an indication for endoscopic resection (ER) for patients with LGD., Results: We retrospectively reviewed 285 lesions initially diagnosed as LGD by endoscopic forceps biopsies (EFB) from 2007 to 2010 in Kyung Hee University Hospital, Seoul, Korea. All patients underwent ER. A total of 285 lesions from 257 patients were assessed. After ER, 239 LGD (83.9 %) showed histological concordance and the remaining 46 (16.1 %) cases revealed an upgraded histology [22 high-grade dysplasia (7.7 %), and 24 differentiated adenocarcinoma (8.4 %)]. Univariate analyses demonstrated that lesion size, erythema, depression, and erosion were significant predictors of upgraded LGD (P < 0.001). Multivariate analysis showed that a lesion size ≥2 cm, erythema, and a depressed-type lesion were independent predictors of upgraded histology (P = 0.014, odds ratio 3.27, 95 % confidence interval 1.28-8.39)., Conclusions: Our data suggest that a substantial number of LGD diagnoses based on EFB were not representative of the entire lesion. We recommend ER if gastric LGD has at least one of the following risk factors: surface erythema and a depressed type regardless of size, or ≥2 cm size regardless of abnormal surface configuration.

Background/aims: Hepatitis B virus (HBV) is the major cause of chronic liver disease in Korea, but viral prevalence has decreased because of hepatitis B vaccination programs. In this study, we investigated longitudinal changes in HBV in fection in the general Korean population., Methods: HBV surface antigen (hepatitis B surface antigen, HBsAg) seropositivity was assessed from the Korea National Health and Nutrition Examination Survey (I to V). In total, 50,140 subjects were tested for serum HBsAg positivity over a period of 12 years (1998 to 2010)., Results: The prevalence of HBsAg seropositivity decreased over the study period. The rates of HBsAg carriers were 4.61% in 1998, 4.60% in 2001, 3.69% in 2005, 3.01% in 2008, and 2.98% in 2010 (p < 0.0001). The reduction in HBV infection rates was more prominent in younger age groups. Among teenagers (10 to 19 years), the percentage of HBsAg carriers decreased from 2.2% in 1998 to 0.12% in 2010 (p < 0.0001). Among those aged 10 to 39 years, the percentage of HBV infection decreased from 4.72% in 1998 to 2.29% in 2010 (p < 0.0001). However, no decreasing trend in HBsAg positivity was observed among those aged 50 or older (p > 0.05). Neither gender nor socioeconomic status were associated with the decreased prevalence of HBsAg carriers., Conclusions: HBV infection has decreased in the Korean population since the advent of vaccination programs. However, the decrease is limited to the younger population, and viral persistence remains in the middle-aged and older population.

This study was performed to estimate the direct medical costs and epidemiology of pneumonia in adults of Korea. We conducted a multi-center, retrospective, observational study and collected data targeting for community-acquired pneumonia patients ( ≥ 50 yr) from 11 hospitals. Costs attributable to the treatment of pneumonia were estimated by reviewing resource utilization and epidemiology data (distribution of pathogen, hospital length of stay, overall outcome) were also collected. A total 693 patients were included; average 70.1 ( ± 10.5) aged, 57.3% male and average 1.16 CURB-65 (confusion, blood urea nitrogen, respiratory rate, blood pressure, age > 65 yr) scored. The pathogen was identified in the 32.9% (228 patients); Streptococcus pneumoniae accounted for 22.4% (51 patients) of identified pathogens. The hospital mortality was 3.2% (especially, for S. pneumoniae was 5.9%) and average length of stay was 9 days. The mean total cost for the treatment of pneumonia was US dollar (USD) 1,782 (SD: USD 1,501). Compared to the cost of all caused pneumonia, that of pneumococcal pneumonia was higher, USD 2,049 ( ± USD 1,919), but not statistically significant. Charge of hospitalization accounted the greatest part of total medical costs. The economic burden of pneumonia was high in Korea, and the prevention of pneumonia should be considered as effective strategy.

Background/aim: As the prevalence of reflux esophagitis increases, so does the use of gastric acid suppressants. This study aimed to document the prevalence of Candida esophagitis (CE) at a single Korean university hospital over the last 5 years and to evaluate its risk factors., Methods: To investigate the prevalence of CE, we conducted a retrospective analysis of 55,314 individuals who underwent a screening esophagogastroduodenoscopy as part of a health check-up between January 2006 and December 2010 at Kyung Hee University Hospital in Seoul, Korea. A total of 250 patients who were treated for CE between January 2008 and August 2011 and 500 age- and sex-matched non-CE patients were enrolled in this study. The rates of recent gastric acid suppression therapy and other well-known risk factors in the two groups were compared., Results: The prevalence of CE was 0.35 % and increased each year (linear-by-linear association, P = 0.001). Univariate analysis showed that gastric acid suppression therapy, malignancy, DM and steroid therapy were related to CE. Multivariate analysis also showed that gastric acid suppression therapy (OR 5.11, 95 % CI 2.92-8.93 and P < 0.001), malignancy (OR 18.68, 95 % CI 6.37-54.75 and P < 0.001), DM (OR 2.67, 95 % CI 1.70-4.21 and P < 0.001) and steroids therapy (OR 6.74, 95 % CI 1.37-33.05 and P = 0.019) were related to CE., Conclusions: The prevalence of CE in Korea is increasing. Also, our results indicate that acid suppression therapy is a meaningful risk factor for CE.

Background/aims: While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea., Methods: The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated., Results: The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001)., Conclusions: The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.

Korea has recently experienced an increasing number of acute hepatitis A cases. We investigated the dynamics of hepatitis A and changes in the mean age of patients in a hospital in Seoul, Korea. Mean age increased consistently from 19 years in 1996 to 30 years in 2009 (P < 0·0001). Between two acute hepatitis A outbreaks in 1998-1999 and in 2008-2009, mean age increased from 23 to 30 years (P < 0·001). However, the hepatitis A clinical outcomes were similar between the outbreaks. Duration of hospital stay, creatinine level and prothrombin time did not differ. Throughout the study period, individuals born in the 1970s and 1980s comprised the largest proportion (84%) of patients. As this susceptible generation ages, the mean age of hepatitis A patients in Korea will increase consistently. However, at present, the impact of increasing age on clinical outcomes is not apparent.