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Background/Aims: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. Methods : We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. Results : The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p

Abstract The aim of our study was to assess the performance of content-based image retrieval (CBIR) for similar chest computed tomography (CT) in obstructive lung disease. This retrospective study included patients with obstructive lung disease who underwent volumetric chest CT scans. The CBIR database included 600 chest CT scans from 541 patients. To assess the system performance, follow-up chest CT scans of 50 patients were evaluated as query cases, which showed the stability of the CT findings between baseline and follow-up chest CT, as confirmed by thoracic radiologists. The CBIR system retrieved the top five similar CT scans for each query case from the database by quantifying and comparing emphysema extent and size, airway wall thickness, and peripheral pulmonary vasculatures in descending order from the database. The rates of retrieval of the same pairs of query CT scans in the top 1–5 retrievals were assessed. Two expert chest radiologists evaluated the visual similarities between the query and retrieved CT scans using a five-point scale grading system. The rates of retrieving the same pairs of query CTs were 60.0% (30/50) and 68.0% (34/50) for top-three and top-five retrievals. Radiologists rated 64.8% (95% confidence interval 58.8–70.4) of the retrieved CT scans with a visual similarity score of four or five and at least one case scored five points in 74% (74/100) of all query cases. The proposed CBIR system for obstructive lung disease integrating quantitative CT measures demonstrated potential for retrieving chest CT scans with similar imaging phenotypes. Further refinement and validation in this field would be valuable.

Abstract The treatment decisions for patients with hepatocellular carcinoma are determined by a wide range of factors, and there is a significant difference between the recommendations of widely used staging systems and the actual initial treatment choices. Herein, we propose a machine learning-based clinical decision support system suitable for use in multi-center settings. We collected data from nine institutions in South Korea for training and validation datasets. The internal and external datasets included 935 and 1750 patients, respectively. We developed a model with 20 clinical variables consisting of two stages: the first stage which recommends initial treatment using an ensemble voting machine, and the second stage, which predicts post-treatment survival using a random survival forest algorithm. We derived the first and second treatment options from the results with the highest and the second-highest probabilities given by the ensemble model and predicted their post-treatment survival. When only the first treatment option was accepted, the mean accuracy of treatment recommendation in the internal and external datasets was 67.27% and 55.34%, respectively. The accuracy increased to 87.27% and 86.06%, respectively, when the second option was included as the correct answer. Harrell’s C index, integrated time-dependent AUC curve, and integrated Brier score of survival prediction in the internal and external datasets were 0.8381 and 0.7767, 91.89 and 86.48, 0.12, and 0.14, respectively. The proposed system can assist physicians by providing data-driven predictions for reference from other larger institutions or other physicians within the same institution when making treatment decisions.

Power Density and cost are the key design criteria for the modern power electronics unit in Electric Vehicles (EVs). EVs widely adopt inductive wireless charging technology, which contains the receiving coil and the AC-DC converter on the vehicle side. However, the vertical space on the chassis for charging electronics is very limited. Moreover, with a non-compact package comes a high damaging probability due to unpredictable road conditions, higher costs, and vehicle integration issues. This research presents the concept of distributed planar magnetics with the integrated rectifier hardware design for the vehicle side charging electronics by combining the concept of planar-distributed magnetics with the design space optimization research. A planar-distributed inductor module consisting of 16 EI cores with PCB-embedded windings was designed, modeled (using a novel high-fidelity model), and fabricated using the design space optimization technique, which resulted in a 66% increase in the power density. This research treated and solved the power density problem as an optimization problem considering every constraint involved and presented a thorough investigation from the design space utilization, power loss, loss and frequency relation along with the magnetostatic and electrostatic analysis perspective. It also provides a comparative study of various materials for the inductor fabrication keeping in view the automotive application environment. Moreover, a hybrid approach (metalcore and FR4) PCB was used instead of a regular FR4 PCB after an in-depth study and performance comparison.

Purpose This study evaluated the quality of surveillance ultrasound (US) for hepatocellular carcinoma (HCC) utilizing fusion imaging. Methods This research involved a secondary analysis of a prospectively recruited cohort. Under institutional review board approval, participants referred for surveillance US who had undergone liver computed tomography (CT) or magnetic resonance imaging (MRI) within the past year were screened between August 2022 and January 2023. After patient consent was obtained, the US visualization score in the Liver Imaging Reporting and Data System was assessed with fusion imaging at the time of examination. This score was compared to that of conventional US using the extended McNemar test. Multivariable logistic regression analysis was used to identify factors independently associated with a US visualization score of B or C. Factors limiting visualization of focal lesions were recorded during fusion imaging. Results Among the 105 participants (mean age, 59±11 years; 66 men), US visualization scores of B and C were assigned to 57 (54.3%) and 17 (16.2%) participants, respectively, by conventional US and 54 (51.4%) and 32 (30.5%) participants, respectively, by fusion imaging. The score distribution differed significantly between methods (P=0.010). Male sex was independently associated with US visualization scores of B or C (adjusted odds ratio, 3.73 [95% confidence interval, 1.30 to 10.76]; P=0.015). The most common reason (64.5%) for lesion non-detection was a limited sonic window. Conclusion Conventional US may underestimate the limitations of the sonic window relative to real-time fusion imaging with pre-acquired CT or MRI in the surveillance of HCC.

Background/Aims Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. Methods This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Results In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (P

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

BackgroundLifestyle modification in patients with nonalcoholic fatty liver disease (NAFLD) is key to improving health outcomes. Mobile health technologies may offer potential effective and efficient health care support to facilitate self-management. ObjectiveThis study aims to develop a lifestyle coaching intervention using a mobile app for patients with NAFLD and evaluate physiological and psychological health outcomes for 6 months. MethodsThis study was a randomized controlled trial. The personalized lifestyle coaching intervention using a mobile app was developed through established guidelines and literature reviews. This intervention consisted of information on NAFLD management, diet and physical activity self-monitoring, and coaching sessions based on patient records and SMS text messages. A total of 102 individuals were enrolled in the study and randomly assigned to the intervention group (n=48) or the control group (n=54). The outcomes were improvements in physiological (weight, liver fat score, aspartate aminotransferase, alanine transferase, and gamma-glutamyl transferase) and clinical outcomes (self-management, NAFLD self-management knowledge, self-efficacy, fatigue, depression, and quality of life). Data were analyzed using descriptive analysis and a linear mixed model to test the effects of the intervention. ResultsAll participants completed the study. The mean age of the participants was 48.9 (SD 13.74) years, 38.2% (39/102) were female participants, and 65.7% (67/102) were married. There were no differences in baseline demographic and clinical data between the intervention and control groups. Changes from baseline to 6 months were significant only within the intervention group for weight (P

Background: Fine particulate matter (PM2.5) is a well-known risk factor for worse outcomes of chronic obstructive pulmonary disease (COPD). However, evidence-based guidance on effective personal behavioural strategies to minimise the effects of PM2.5 is limited. This study aimed to assess the effectiveness of a behavioural intervention in reducing PM2.5 exposure and improving clinical outcomes in patients with COPD. Materials and Methods: Participants were 1:1 randomised, and the intervention group received a behavioural intervention consisting of five activities, while the control group received usual care. The participants were followed up for 9 months. The primary outcomes were differences in the score of St. George’s Respiratory Questionnaire for patients with COPD (SGRQ-C) and COPD assessment test (CAT) from baseline. Results: A total of 106 participants were enrolled and 102 completed the study. At the end of the study, the intervention group showed significant improvements in the primary outcomes compared to the control group, with a group difference of −5.9 in the reduction of total SGRQ-C (−3.4 vs. 2.5; p = 0.049) and −3.8 in the CAT score (−1.2 vs. 2.7; p = 0.001). Participants with good adherence to the intervention demonstrated a greater extent of improvement in CAT score and lower PM2.5 levels compared to those who had poor adherence or were in the control group. Regular checking of air quality forecasts was significantly associated with a reduction in CAT scores among all the intervention activities. Conclusion: Individual-level behavioural interventions can be an effective strategy for mitigating the health hazards associated with PM2.5.ClinicalTrials.gov Identifier: NCT04878367.

Background/Aims: Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD. Methods: We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. Results: The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend

Background/Aim The profile of patients with hepatocellular carcinoma (HCC) has changed globally; the role of etiology in predicting prognosis of HCC patients remains unclear. We aimed to analyze the characteristics and prognosis of Korean patients with HCC according to disease etiology. Methods This retrospective observational study included patients diagnosed with HCC between 2010 and 2014 in a single center in Korea. Patients with HCC aged

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths, posing a substantial threat to global public health. Viruses evolve different strategies to antagonize or evade host immune responses. While ectopic expression of SARS-CoV-2 accessory protein ORF6 blocks interferon (IFN) production and downstream IFN signaling, the role of ORF6 in IFN signaling during bona fide viral infection of respiratory cells is unclear. By comparing wild-type (WT) and ORF6-deleted (ΔORF6) SARS-CoV-2 infection and IFN signaling in respiratory cells, we found that ΔORF6 SARS-CoV-2 replicates more efficiently than WT virus and, thus, stimulates more robust immune signaling. Loss of ORF6 does not alter innate signaling in infected cells: both WT and ΔORF6 virus induce delayed IFN responses only in bystander cells. Moreover, expression of ORF6 in the context of SARS-CoV-2 infection has no effect on Sendai virus-stimulated IFN induction: robust translocation of IRF3 is observed in both SARS-CoV-2 infected and bystander cells. Furthermore, IFN pretreatment potently blocks WT and ΔORF6 virus replication similarly, and both viruses fail to suppress the induction of interferon-stimulated genes (ISGs) upon IFN-β treatment. However, upon treatment with IFN-β, only bystander cells induce STAT1 translocation during infection with WT virus, whereas ΔORF6 virus-infected cells now show translocation. This suggests that under conditions of high IFN activation, ORF6 can attenuate STAT1 activation. These data provide evidence that ORF6 is not sufficient to antagonize IFN production or IFN signaling in SARS-CoV-2-infected respiratory cells but may impact the efficacy of therapeutics that stimulate innate immune pathways. IMPORTANCE Previous studies identified several SARS-CoV-2 proteins, including ORF6, that antagonize host innate immune responses in the context of overexpression of viral proteins in non-respiratory cells. We set out to determine the role of ORF6 in IFN responses during SARS-CoV-2 infection of respiratory cells. Using a deletion strain, we observed no reduction of infection and no difference in evasion of IFN signaling, with responses limited to bystander cells. Moreover, stimulation of Sendai virus-induced IFN production or IFN-β-stimulated ISG expression was comparable between SARS-CoV-2 virus and SARS-CoV-2 lacking ORF6 virus, suggesting that ORF6 is not sufficient to counteract IFN induction or IFN signaling during viral infection.

Abstract Background The prognostic value of bronchoalveolar lavage (BAL) fluid analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP) has not been well elucidated. We aimed to investigate the prognostic implication of BAL fluid analysis in non-HIV patients with PJP. Methods The data of 178 non-HIV patients diagnosed with PJP based on the results of the polymerase chain reaction assay of BAL fluid specimens between April 2018 and December 2020 were retrospectively reviewed. The clinical characteristics, laboratory findings, and BAL fluid analysis results of patients who died within 90 days after hospital admission were compared. Results Twenty patients (11.2%) died within 90 days from admission. The neutrophil count in BAL fluid was significantly higher (median 22.0%, interquartile range [IQR] 2.0–46.0% vs. median 6.0%, IQR 2.0–18.0%, P = 0.044), while the lymphocyte count was significantly lower (median 24.0%, IQR 7.0–37.0% vs. median 41.0%, IQR 22.5–60.5%, P = 0.001) in the non-survivor group compared with that in the survivor group. In the multivariate analysis, the C-reactive protein level (odds ratio [OR] 1.093, 95% confidence interval [CI] 1.020–1.170, P = 0.011) and a BAL fluid lymphocyte count of ≤ 30% (OR 3.353, 95% CI 1.101–10.216, P = 0.033) were independently associated with mortality after adjusting for albumin and lactate dehydrogenase levels. Conclusion A low lymphocyte count in BAL fluid may be a predictor of mortality in non-HIV patients with PJP.

Abstract The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting β2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV1), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. Methods: Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines. Results: The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p

Pulmonary hypertension (PH) is a condition of increased blood pressure in the pulmonary arteries and is diagnosed with an increased a mean pulmonary artery pressure ≥25 mm Hg. This condition may be associated with multiple clinical situations. Based on pathophysiological mechanisms, clinical presentation, hemodynamic profiles, and treatment strategies, the patients were classified into five clinical groups. Although there have been major advances in the management of PH, it is still associated with significant morbidity and mortality. The diagnosis and treatment of PH have been performed mainly by following European guidelines, even in Korea because the country lacks localized PH guidelines. European treatment guidelines do not reflect the actual status of Korea. Therefore, the European diagnosis and treatment of PH have not been tailored well to suit the needs of Korean patients with PH. To address this issue, we developed this guideline to facilitate the diagnosis and treatment of PH appropriately in Korea, a country where the consensus for the diagnosis and treatment of PH remains insufficient. This is the first edition of the guidelines for the diagnosis and treatment of PH in Korea, and it is primarily based on the ‘2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.’ with the acceptance and adaptation of recent publications of PH.

Background: Idiopathic pulmonary fibrosis (IPF) is a known risk factor for venous thromboembolism (VTE). However, it is currently unknown which factors are associated with an increase of VTE in patients with IPF. Objectives: We estimated the incidence of VTE in patients with IPF and identified clinical characteristics related to VTE in patients with IPF. Design and methods: De-identified nationwide health claim data from 2011 to 2019 was collected from the Korean Health Insurance Review and Assessment database. Patients with IPF were selected if they had made at least one claim per year under the J84.1 [ International Classification of Diseases and Related Health Problems , 10th Revision (ICD-10)] and V236 codes of rare intractable diseases. We defined the presence of VTE as at least one claim of pulmonary embolism and deep vein thrombosis ICD-10 codes. Results: The incidence rate per 1000 person-years of VTE was 7.08 (6.44–7.77). Peak incidence rates were noted in the 50–59 years old male and 70–79 years old female groups. Ischemic heart disease, ischemic stroke, and malignancy were associated with VTE in patients with IPF, with an adjusted hazard ratio (aHR) of 1.25 (1.01–1.55), 1.36 (1.04–1.79), and 1.53 (1.17–2.01). The risk for VTE was increased in patients diagnosed with malignancy after IPF diagnosis (aHR = 3.18, 2.47–4.11), especially lung cancer [hazard ratio (HR) = 3.78, 2.90–4.96]. Accompanied VTE was related to more utilization of medical resources. Conclusion: Ischemic heart disease, ischemic stroke, and malignancy, especially lung cancer, were related to higher HR for VTE in IPF.

Background/Aims Although international guidelines for bronchiectasis management have been published in Western countries, there is a lack of data about their application in Asian populations including patients with different phenotypes. We aimed to investigate the current status of bronchiectasis management in Asian populations. Methods A nationwide questionnaire survey was performed of Asian respiratory specialists from South Korea, Japan, Taiwan, Singapore, Vietnam, and Sri Lanka. Participants were invited by e-mail to answer a questionnaire comprising 25 questions based on international guidelines for the management of bronchiectasis. Results A total of 221 physicians participated in the survey. About half of them were Korean (50.2%), with the next most common nationalities being Japanese (23.1%), Taiwanese (13.6%), and Singaporean (7.7%). Only 18 (8.1%) responders had local guidelines for bronchiectasis. While 85 (38.5%) responders checked sputum acid-fast bacillus smear/culture about 1 to 3 times per year, only a small proportion of responders routinely performed a serum immunoglobulin test (36/221, 16.3%) or evaluated for allergic bronchopulmonary aspergillosis (41/221, 18.6%). Less than half (43.4%) of responders performed eradication treatment in patients with drug-sensitive Pseudomonas aeruginosa infection, mainly due to the limited availability of inhaled antibiotics (34.8%). In addition, 58.6% of responders considered physiotherapy such as airway clearance and pulmonary rehabilitation. Conclusions Discrepancies might exist between guideline recommendations and practice for bronchiectasis management in Asian populations, partly due to the limited availability of treatment in each country. The development of local guidelines that consider the phenotypes and situation will help to standardize and improve the management of bronchiectasis.

Abstract Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P

Abstract Background Sarcopenia is a significant indicator of the severity of non‐alcoholic fatty liver disease. We investigated whether sarcopenia could identify subgroups with different risk of liver fibrosis and atherosclerotic cardiovascular disease (ASCVD) among subjects with metabolic dysfunction‐associated fatty liver disease (MAFLD). Methods Subjects from the Korea National Health and Nutrition Examination Survey 2008–2011 were selected (n = 8361). Sarcopenia was defined using the sarcopenia index. Hepatic steatosis was defined as a fatty liver index ≥30. Significant liver fibrosis was defined as a fibrosis‐4 index (FIB‐4) ≥2.67 or the highest quartile of non‐alcoholic fatty liver disease fibrosis score (NFS). High probability of ASCVD was defined as ASCVD risk score >10%. Results The mean age was 48.5 ± 15.6 years, and 42.6% of subjects were male. The prevalence of MAFLD was 37.3% (n = 3116 of 8361), and the proportion of sarcopenic subjects was 9.9% among those with MAFLD. After adjusting for confounders, the risk of significant liver fibrosis significantly increased from non‐sarcopenic subjects with MAFLD [odds ratio (OR) = 1.57 by FIB‐4 and 2.13 by NFS] to sarcopenic subjects with MAFLD (OR = 4.51 by FIB‐4 and 5.72 by NFS), compared with subjects without MAFLD (all P

Abstract Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642–0.8373) and 0.7156 (95% CI, 0.7024–0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.

Background: Polycystic liver disease (PCLD) is the most common extrarenal manifestation of polycystic kidney disease. There is an urgent need to assess the efficacy and safety of nonsurgical modalities to relieve symptoms and decrease the severity of PCLD. Herein, we aimed to evaluate the efficacy of the nonsurgical treatment of PCLD and the quality of life of affected patients. Methods: PubMed, Ovid, MEDLINE, EMBASE, and the Cochrane Library were searched for studies on the nonsurgical modalities, either medications or radiological intervention to manage PCLD. Treatment efficacy, adverse events (AEs), and patient quality of life were evaluated. Results: In total, 27 studies involving 1037 patients were selected. After nonsurgical treatment, liver volume decreased by 259 ml/m [mean change (Δ) of 6.22%] and the effect was higher in the radiological intervention group [−1617 ml/m (−15.49%)] than in the medication group [−151 ml/m (−3.78%)]. The AEs and serious AEs rates after overall nonsurgical treatment were 0.50 [95% confidence interval (CI): 0.33–0.67] and 0.04 (95% CI: 0.01–0.07), respectively. The results of the SF-36 questionnaire showed that PCLD treatment improved physical function [physical component summary score of 4.18 (95% CI: 1.54–6.83)] but did not significantly improve mental function [mental component summary score of 0.91 (95% CI: −1.20 to 3.03)]. Conclusion: Nonsurgical treatment was effective and safe for PCLD, but did not improve the quality of life in terms of mental health. Radiological intervention directly reduces hepatic cysts, and thus they should be considered for immediate symptom relief in patients with severe symptoms, whereas medication might be considered for maintenance treatment. Registration number: PROSPERO (International Prospective Register of Systematic Reviews) CRD42021279597

Background/Aims Air trapping is associated with unfavorable outcomes in chronic obstructive pulmonary disease (COPD). The present study evaluated the association between longitudinal changes in air trapping with pulmonary function, computed tomography (CT) parameters and exacerbation. Methods Patients enrolled in the Korean Obstructive Lung Disease (KOLD) study cohort from June 2005 to October 2015 were included. The study patients were categorized into four groups according to the change in residual volume to total lung capacity ratio (RV/TLC) over 3 years. The RV/TLC was considered abnormal when it was ≥ 40% and normal when it was < 40%. Results A total of 279 patients were categorized into four groups: 76 in the “normal to normal” (N→N) group, 34 in the “abnormal to normal” (A→N) group, 33 in the “normal to abnormal” (N→A) group, and 136 in the “abnormal to abnormal” (A→A) group. For forced expiratory volume in 1 second and forced vital capacity (FVC), respectively, group A→N showed a large increase of 266 mL (p < 0.001) and 381 mL (p < 0.001), group N→A showed a marked decrease of 216 mL (p < 0.001) and 332 mL(p = 0.029), and group A→A showed a decrease of 16 mL (p = 0.426) and 6 mL (p = 0.011) compared to group N→N. Group A→N showed a significant decrease of −0.013 in expiratory to inspiratory ratio of the mean lung density (p < 0.001), while group A→N showed an increase of 0.005 (p < 0.001). Conclusions Patients with COPD whose RV/TLC changed from normal to abnormal showed deterioration of pulmonary function and worsening of CT parameters simultaneously.

Background/Aims The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT. Methods Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of

Purpose – In cities with high density, heat is often trapped between buildings which increases the frequency and intensity of heat events. Researchers have focused on developing strategies to mitigate the negative impacts of heat in cities. Adopting green infrastructure and cooling pavements are some of the many ways to promote thermal comfort against heat. The purpose of this study is to improve microclimate conditions and thermal comfort levels in high-density living conditions in Seoul, South Korea. Design/methodology/approach – This study compares six design alternatives of an apartment complex with different paving and planting systems. It also examines the thermal outcome of the alternatives under normal and extreme heat conditions to suggest strategies to secure acceptable thermal comfort levels for the inhabitants. Each alternative is analyzed using ENVI-met, a software program that simulates microclimate conditions and thermal comfort features based on relationships among buildings, vegetation and pavements. Findings – The results indicate that grass paving was more effective than stone paving in lowering air temperature and improving thermal comfort at the near-surface level. Coniferous trees were found to be more effective than broadleaf trees in reducing temperature. Thermal comfort levels were most improved when coniferous trees were planted in paired settings. Practical implications – Landscape elements show promise for the improvement of thermal conditions because it is much easier to redesign landscape elements, such as paving or planting, than to change fixed urban elements like buildings and roads. The results identified the potential of landscape design for improving microclimate and thermal comfort in urban residential complexes. Originality/value – The results contribute to the literature by examining the effect of tree species and layout on thermal comfort levels, which has been rarely investigated in previous studies.

Abstract Background Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. Methods This was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV1, the St. George’s Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events. Results A total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV1, reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group. Conclusions Dual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV1 than those with higher FEV1.

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p < 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size < 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.

Background/Aims Ledipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients. Methods Between 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12). Results Most patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×106 IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%). Conclusions LDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

Identification of non-alcoholic steatohepatitis (NASH) with high activity and fibrosis is a major priority in patients with non-alcoholic fatty liver disease. We validated the predictive value of the FibroScan-aspartate aminotransferase (FAST) score and other non-invasive fibrosis surrogates in predicting high-risk NASH criteria. This multicenter retrospective study recruited 251 biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients (132 [52.6%] men) between 2011 and 2014. The FAST score was calculated using transient elastography data and aspartate aminotransferase (AST) levels. The NAFLD fibrosis score (NFS), fibrosis-4 index (FIB-4), and AST to platelet ratio index (APRI) were calculated using biochemical data. The area under the receiver operating characteristic curves (AUCs) of the FAST score, liver stiffness, NFS, FIB-4, and APRI were 0.752, 0.718, 0.609, 0.650, and 0.722 for NAFLD activity score (NAS) ≥5 (n = 117, 46.6%); 0.788, 0.754, 0.649, 0.701, and 0.747 for fatty liver inhibition of progression-NASH with histologic activity ≥3 (n = 202, 80.5%); 0.807, 0.806, 0.691, 0.732, and 0.760 for severe disease with activity ≥3 and/or fibrosis ≥3 (n = 132, 52.6%); and 0.714, 0.812, 0.748, 0.738, and 0.669 for NASH with NAS ≥4 and fibrosis ≥2 (n = 70, 27.9%), respectively. The FAST score had the highest AUC for the most high-risk NASH criteria, except for in predicting NAS ≥4 and fibrosis ≥2. The liver stiffness value showed consistently acceptable performance in predicting all high-risk NASH criteria. The FAST score has acceptable performance in identifying high-risk NASH. However, liver stiffness alone was not inferior to the FAST score.

Background and AimsAir trapping is a predictive index for a decline in lung function and mortality in patients with chronic obstructive pulmonary disease (COPD). However, the role of air trapping in COPD exacerbation has rarely been studied. Therefore, this study aimed to investigate the impact of air trapping as a continuous parameter on COPD exacerbation.Materials and MethodsTo evaluate air trapping, we identified the ratio of residual volume (RV) to total lung capacity (TLC) of patients with COPD from the Korean COPD Subgroup Study (KOCOSS) cohort, which is a multicenter-based, prospective, consecutive cohort in Korea. The primary outcome was a development of COPD exacerbation during 3 years of follow-up.ResultsOf 2,181 participants, 902 patients measured the RV/TLC ratio in the baseline enrollment, and 410 were evaluated for assessing the development of COPD exacerbation. Of 410 patients, the rate of moderate to severe exacerbation and severe exacerbation was 70.7% and 25.9%. A 10% increase of RV/TLC ratio increased the risk of the moderate to severe exacerbation by 35% and severe exacerbation by 36%. In subgroup analysis, an interaction effect between triple inhaled therapy and the RV/TLC ratio for severe exacerbation nullified the association between the RV/TLC ratio and severe exacerbation (p for interaction = 0.002).ConclusionsIn this prospective cohort study, we found that air trapping (representing RV/TLC ratio as a continuous parameter) showed an association with an increased risk of COPD exacerbation, particularly in patients who have not undergone triple inhaler therapy.

Background/Aims: The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria have been used to assess treatment responses for hepatocellular carcinoma (HCC) patients. We investigated which criteria provides better survival predictions in HCC patients treated with transarterial radioembolization (TARE). Methods: In total, 102 patients with unresectable intrahepatic HCC, who were treated with TARE between 2012 and 2017, were reviewed retrospectively. The treatment response after TARE was evaluated at 1, 3, and 6 months by the mRECIST and RECIST 1.1. Responders were defined as patients with complete or partial responses by each criterion. Results: The median age of 83 men and 19 women was 64.3 years. The median alpha-fetoprotein and des-gamma-carboxy prothrombin levels were 37.1 ng/mL and 1,780.0 mAU/mL, respectively. The median maximal tumor size was 8.3 cm, and multiple tumors were observed in 36 patients (35.3%). During the follow-up period (median, 20.7 months), 21 patients (20.6%) died, with a mean survival time of 55.5 months. The cumulative survival rate was 96.1% at 6 months and 89.3% at 12 months. Responders, defined by the mRECIST at 1, 3, and 6 months after TARE, showed better survival outcomes than nonresponders (hazard ratio [HR]=5.736, p=0.008 at 1 month; HR=3.145, p=0.022 at 3 months, and HR=2.887, p=0.061 at 6 months). The survival rates of responders and nonresponders defined by the RECIST 1.1 were similar (all p>0.05). Conclusions: Response evaluations that use the mRECIST provide more accurate prognoses than those that use the RECIST 1.1 in HCC patients treated with TARE.

Background The Bronchiectasis Health Questionnaire (BHQ) is a simple and repeatable, self-reporting health status questionnaire for bronchiectasis. We have translated the original version of the BHQ into Korean using a standardized methodology. The purpose of this study was to assess the validity of the Korean version of the BHQ (K-BHQ) with Korean patients. Methods Stable state patients with bronchiectasis from two academic hospitals were enrolled in this study. The validity was assessed by investigating the relationship between the K-BHQ scores and the Korean version of the Chronic Obstructive Pulmonary Disease Assessment Test (K-CAT) scores. We also investigated the relationship between the K-BHQ scores and other variables of the modified Medical Research Council’s (mMRC) dyspnea scale, lung function, and exacerbations. Results A total of 126 patients with bronchiectasis were enrolled. The mean age was 64.3 (standard deviation [SD], 9.7). Women comprised 53.2% of the patients. The mean forced expiratory volume in one second (FEV1) was 60% of the predicted value (SD, 18.9%); the mean K-CAT score was 17.6 (SD, 9.1). The K-BHQ scores correlated strongly with the K-CAT scores (r=–0.656, p1 (r=0.406, p

Background/Aims Few studies have attempted to interpret unusually high predicted pulmonary function test results. This study aimed to investigate the demographic features of patients with an unusually high predicted pulmonary function. Methods The demographic data of subjects who underwent pulmonary function testing at a tertiary referral hospital during between January 2011 and December 2011 were retrospectively reviewed. Results Of the 68,693 included patients, 55 (0.08%) had a percent predicted forced expiratory volume in 1 second or forced vital capacity ≥ 140%. These patients had a relatively older median age (72 years vs. 54 years, p < 0.001), female predominance (65.5% vs. 42.5%, p = 0.001), lower body weight (52.5 kg vs. 64.5 kg, p < 0.001) and shorter height (148.4 cm vs. 164.2 cm, p < 0.001). Furthermore, 6.1% of women older than 80 years with weight < 50 kg and height < 150 cm had a high predicted pulmonary function. Conclusions A high predicted pulmonary function is not rare among elderly subjects with a small body size. Physicians should consider the demographics of the examinees, especially those of minority populations, particularly as the test results might be determined using an incorrect reference equation.

Background/Aims Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but there is much controversy about TACE refractoriness. The aim of this study was to identify trends in the actual clinical application of TACE and recognition of TACE refractoriness by Korean experts. Methods In total, 17 questionnaires on TACE refractoriness were administered to 161 clinicians via an online survey. Multiple answers were allowed for some questions. Results Most clinicians agreed that there is a need for standardization of TACE application through specific scoring systems (n=124, 77.0%). TACE refractoriness was predominantly expected by participants when recurrences were detected within 1 month (n=70, 43.5%), there were 4 to 6 tumors (n=77, 47.8%), the maximal tumor size was 3–5 cm (n=49, 30.4%), and when there was insufficient tumor necrosis despite TACE being repeated more than three times (n=78, 48.4%). Overall, sorafenib therapy (n=137) and radiotherapy (n=114) were preferred when repeated TACE was considered ineffective. Conclusions Treatment of HCC is often based on the clinical judgment of clinicians because of the heterogeneity among individuals. Experts need to continue discussions on the standardization and sub-classification of HCC treatment guidelines in Korea.

This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9–7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.

Despite the burden of bronchiectasis, there is little data from South Korea regarding asymptomatic bronchiectasis. We aimed to investigate the prevalence of bronchiectasis based on computed tomography (CT) findings, with emphasis on asymptomatic bronchiectasis (CT-proven) and its related factors. We analysed data of individuals who underwent chest CT at a South Korean health screening centre from 2016 to 2017. The prevalence of bronchiectasis was evaluated and adjusted by sex, age, and corresponding year for the Korean general population. Logistic regression analysis was performed to identify factors related to asymptomatic bronchiectasis by comparison between a group without bronchiectasis and a group with symptomatic bronchiectasis. Among the 27 617 subjects screened, 1005 were diagnosed with bronchiectasis based on CT findings, representing an adjusted prevalence of 2329 out of 100 000. The adjusted prevalence of asymptomatic bronchiectasis was 1235 out of 100 000, and that of symptomatic bronchiectasis was 1094 out of 100 000. Compared with the non-bronchiectasis group, the factors related to asymptomatic bronchiectasis were female sex (OR 1.41; 95% CI 1.18–1.70), older age (OR 1.06; 95% CI 1.05–1.07), comorbid liver disease (OR 1.32; 95% CI 1.07–1.63) or COPD (OR 4.99; 95% CI 2.88–8.64), history of tuberculosis (OR 1.98; 95% CI 1.46–2.68) and low forced expiratory volume in 1 s (FEV1; OR 0.99; 95% CI 0.98–0.998). In South Korea, the prevalence of asymptomatic bronchiectasis appeared higher than that of symptomatic bronchiectasis. Female sex, older age, liver disease, COPD, history of tuberculosis and low FEV1 may be the factors related to asymptomatic bronchiectasis.

Abstract Recent studies have identified the mutational landscape of pancreatic cancer and suggested tumor‐specific subtypes. However, the major hurdle against personalized treatment is the difficulty to obtain sufficient cancer tissues from most inoperable cases. We investigated whether patient‐derived conditionally reprogrammed cells (CRCs) can be constructed using a small piece of tumor tissue using endoscopic ultrasound (EUS)‐guided fine needle biopsy (FNB). Thirty patients with pancreatic solid mass (mean size, 34.6 mm) were enrolled prospectively. Among 22 patients who were diagnosed with pancreatic ductal adenocarcinoma, we established patient‐derived pancreatic cancer cell lines from eight patients (36.4%). Immunofluorescence colony staining for CRCs showed that the cytoplasm of cancer cells was clearly stained with anti‐cytokeratin 19 monoclonal antibody. In the soft agar colony formation assay, CRCs formed colonies compared with the negative control by day 15. In vivo, implanted CRCs showed tumor engraftment and hematoxylin and eosin staining showed pancreatic cancer ductal structure. All established CRCs showed a KRAS mutation. In conclusion, we established patient‐derived pancreatic cancer cell lines with a small tumor tissue obtained by EUS‐FNB. With in vitro drug sensitivity and genomic studies, established patient‐derived cell lines can be used in identification of new targets for diagnosis and treatment of pancreatic cancer.

Background The utility of computed tomography (CT) in the differential diagnosis of patients with chronic obstructive pulmonary disease (COPD) exacerbation remains uncertain. However, due to the low cost associated with CT scan along with the impact of Koreas' health insurance system, there has been a rise in the number of CT scans in the patients with initial diagnosis of COPD exacerbations. Therefore, the utility of CT in the differential diagnosis was investigated to determine whether performing CT scans affect the clinical outcomes of the patients with an initial diagnosis of COPD exacerbation. Methods This study involved 202 COPD patients hospitalized with an initial diagnosis of COPD exacerbation. We evaluated the change in diagnosis or treatment after performing a CT scan, and compared the clinical outcomes of patient groups with vs. without performing CT (non-CT group vs. CT group). Results After performing CT, the diagnosis was changed for two (3.0%) while additional diagnoses were made for 27 of the 64 patients (42.1%). However, the treatment changed for only one (1.5%), and six patients (9.3%) received supplementary medication. There were no difference in the median length of hospital stay (8 [6–13] days vs. 8 [6–12] days, p=0.786) and intensive care unit care (14 [10.1%] vs. 11 [16.7%], p=0.236) between the CT and non-CT groups, respectively. These findings remained consistent even after the propensity score matching. Conclusion Utility of CT in patients with acute COPD exacerbation might not be helpful; therefore, we do not recommend chest CT scan as a routine initial diagnostic tool.

Chronic thromboembolic pulmonary hypertension is potentially curable with a pulmonary endarterectomy. However, approximately 20% of patients have persistent pulmonary hypertension after pulmonary endarterectomy, which is a major risk factor for postoperative death. Here, we report a 34-year-old woman who suffered persistent severe pulmonary hypertension following a successful pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) and atrial septostomy were successfully performed as rescue treatments, and active rehabilitation during ECMO was prescribed to facilitate recovery.

Background Although extracorporeal membrane oxygenation (ECMO) has been used for the treatment of acute high-risk pulmonary embolism (PE), there are limited reports which focus on this approach. Herein, we described our experience with ECMO in patients with acute high-risk PE. Methods We retrospectively reviewed medical records of patients diagnosed with acute high-risk PE and treated with ECMO between January 2014 and December 2018. Results Among 16 patients included, median age was 51 years (interquartile range [IQR], 38 to 71 years) and six (37.5%) were male. Cardiac arrest was occurred in 12 (75.0%) including two cases of out-of-hospital arrest. All patients underwent veno-arterial ECMO and median ECMO duration was 1.5 days (IQR, 0.0 to 4.5 days). Systemic thrombolysis and surgical embolectomy were performed in seven (43.8%) and nine (56.3%) patients, respectively including three patients (18.8%) received both treatments. Overall 30-day mortality rate was 43.8% (95% confidence interval, 23.1% to 66.8%) and 30-day mortality rates according to the treatment groups were ECMO alone (33.3%, n=3), ECMO with thrombolysis (50.0%, n=4) and ECMO with embolectomy (44.4%, n=9). Conclusions Despite the vigorous treatment efforts, patients with acute high-risk PE were related to substantial morbidity and mortality. We report our experience of ECMO as rescue therapy for refractory shock or cardiac arrest in patients with PE.

BACKGROUND: Better outcomes have been observed in patients with acute unprovoked than provoked pulmonary embolism (PE). Prognostic biomarkers were studied in heterogeneous patient population and were not verified in patients with unprovoked PE. METHODS: Patients diagnosed with unprovoked acute PE from 2010 to 2017 at Asan Medical Center, South Korea, were analyzed retrospectively. Adverse composite outcomes were defined as thrombolysis, thrombectomy, extracorporeal membrane oxygenation, or death. Venous blood samples were collected at the first visit before anticoagulant treatment. Biomarkers associated with composite outcomes were analyzed and compared with preexisting risk models. RESULTS: This study included 265 patients (48.7% male) with a median age of 66.0 (interquartile range 52.0, 75.0) years. Composite outcomes occurred in 20 (7.5%) patients. Hemoglobin, uric acid, and glucose were significantly and independently associated with adverse composite outcomes. This biomarker model showed the highest prognostic accuracy for adverse composite outcomes, with an area under the curve of 0.806 (95% confidence interval: 0.702–0.911,P < 0.001), which was significantly better than that of PE severity index (PESI) or simplified PESI, and comparable to that of the European Society of Cardiology (ESC) risk classification. CONCLUSIONS: The biomarker model including hemoglobin, uric acid, and glucose has good prognostic performance comparable to the ESC risk classification while PESI or simplified PESI score was not useful in unprovoked PE.

Background Antiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS. Methods We retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006–2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups. Results On multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025–162.343), low PE severity index (OR, 0.948; 95% CI, 0.917–0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040–1.307). Model II included age (OR, 0.930; 95% CI, 0.893–0.969) and aPTT (OR, 1.104; 95% CI, 1.000–1.217). Conclusion We conclude that patients with first unprovoked PE with hemoptysis and are age

Summary: There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.

Abstract Background Blood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies. However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated. This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients. Methods In total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included. Patients were stratified according to a cut-off of 300 cells/μL, and the association between eosinophil changes and all-cause mortality was analysed. The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George’s Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups. Results Patients were stratified into three groups according to the blood eosinophil cut-off: persistently

Purpose The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. Methods We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children’s Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. Results The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. Conclusion Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.

Hepatitis C virus (HCV) is a positive-strand RNA virus replicating in a membranous replication organelle composed primarily of double-membrane vesicles (DMVs) having morphological resemblance to autophagosomes. To define the mechanism of DMV formation and the possible link to autophagy, we conducted a yeast two-hybrid screening revealing 32 cellular proteins potentially interacting with HCV proteins. Among these was the Receptor for Activated Protein C Kinase 1 (RACK1), a scaffolding protein involved in many cellular processes, including autophagy. Depletion of RACK1 strongly inhibits HCV RNA replication without affecting HCV internal ribosome entry site (IRES) activity. RACK1 is required for the rewiring of subcellular membranous structures and for the induction of autophagy. RACK1 binds to HCV nonstructural protein 5A (NS5A), which induces DMV formation. NS5A interacts with ATG14L in a RACK1 dependent manner, and with the ATG14L-Beclin1-Vps34-Vps15 complex that is required for autophagosome formation. Both RACK1 and ATG14L are required for HCV DMV formation and viral RNA replication. These results indicate that NS5A participates in the formation of the HCV replication organelle through interactions with RACK1 and ATG14L.

Astrocytes, characterized by a satellite-like morphology, are the most abundant type of glia in the central nervous system. Their main functions have been thought to be limited to providing homeostatic support for neurons, but recent studies have revealed that astrocytes actually actively interact with local neural circuits and play a crucial role in information processing and generating physiological and behavioral responses. Here, we review the emerging roles of astrocytes in many brain regions, particularly by focusing on intracellular changes in astrocytes and their interactions with neurons at the molecular and neural circuit levels.

Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and/or clinical trials.