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BACKGROUND The pharmacokinetic profile of vancomycin is highly variable, especially in critically ill patients. Various deep learning models have been successful so far in the decision-making system that predicts the vancomycin therapeutic drug monitoring (TDM) level in patients in the intensive care unit (ICU). OBJECTIVE We aimed to establish an ideal model by comparing and integrating methods in the decision-making system that predicts the vancomycin TDM level in ICU patients. METHODS We proposed novel deep learning model, the joint multilayer perceptron (JointMLP) for predicting vancomycin TDM level and compared the performance of a population pharmacokinetic (PPK) model, extreme gradient boosting, and TabNet, respectively, with data collected from Dongguk University Ilsan Hospital (DUIH) and Kangwon National University Hospital (KNUH). RESULTS Of the 977 DUIH datasets, 97 were used as the test set while the remaining 879 were used as the training data set. The external validation subject was data from 1,429 KNUH subjects. For the external data set, all models were found to have significantly higher predictive power than PPK. However, in internal datasets, the JointMLP model showed significantly better performance in predicting vancomycin TDM than the PPK model (root mean squared error 8.27 vs. 10.38, P < 0.01). The JointMLP model showed better predictive performance than other models, including the PPK model, in the external dataset. The most influential variables in TDM prediction were the vancomycin volume of distribution, sex, and height in both internal and external datasets. These variables consistently had high SHAP values in both datasets CONCLUSIONS JointMLP implementation for clinical use will not only provide optimal vancomycin doses but also provide many improvements in itself as the data are continuously updated, which will result in continued increments in accuracy.

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant ( P < 0.00015) when adjusting for lead GWAS single-nucleotide polymorphisms A common gasdermin B ( GSDMB) splice variant (rs11078928) previously associated with a decreased risk for asthma was nominally associated with a decreased risk for COPD [minor allele frequency (MAF) = 0.46, P = 1.8e-4]. Two stop variants in coiled-coil α-helical rod protein 1 ( CCHCR1), a gene involved in regulating cell proliferation, were associated with COPD (both P < 0.0001). The SERPINA1 Z allele was associated with a random-effects odds ratio of 1.43 for COPD (95% confidence interval = 1.17–1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants and further define the role of coding variants in COPD pathogenesis.

Background: Previous studies reported a significant association between pneumonia outcome and the respiratory microbiome. There is increasing interest in the roles of bacterial extracellular vesicles (EVs) in various diseases. We studied the composition and function of microbiota-derived EVs in the plasma of patients receiving mechanical ventilation to evaluate whether they can be used as a diagnostic marker and to predict clinical outcomes. Methods: Plasma samples (n = 111) from 59 mechanically ventilated patients (41 in the pneumonia group; 24 in the nursing home and hospital-associated infection [NHAI] group) were prospectively collected on days one and seven. After isolating the bacterial EVs from plasma samples, nucleic acid was extracted for 16S rRNA gene pyrosequencing. The samples were evaluated to determine the α and β diversity, bacterial composition, and predicted functions. Results: Principal coordinates analysis revealed significantly different clustering of microbial EVs between the pneumonia and non-pneumonia groups. The proportions of Lactobacillus, Cutibacterium, and Sphingomonas were significantly different between the pneumonia and non-pneumonia groups. In addition, the abundances of Lactobacillus and Bifidobacterium were significantly higher in the non-NHAI than the NHAI group. In the analysis of β diversity, the structure of microbial EVs differed significantly different between 28-day survivors and non-survivors (Bray-Curtis distance, p = 0.014). Functional profiling revealed significant differences between the pneumonia and non-pneumonia groups. The longitudinal change in predicted functions of microbial EV genes showed a significant difference between 28-day survivors and non-survivors. Conclusions: Bacterial microbiota–derived EVs in the plasma have potential as diagnostic and prognostic markers for patients receiving mechanical ventilation. Further large prospective studies are needed to determine the clinical utility of plasma microbiota-EVs in intubated patients.

679 Background: During the last decade, the survival outcomes of patients with pancreatic cancer (PC) have improved. We aimed to establish a model of which clinical factors contributed to improved survival in PC patients who underwent upfront surgery. Methods: Public data from the KOREA Health Insurance Review and Assessment (HIRA) database were collected. Medical records in a single tertiary center were also retrospectively reviewed between 2013 and 2018. Enrolled patients were those who underwent curative upfront surgery for PC. Results: A total of 12,146 patients in HIRA data and 267 patients in single-center data were collected. The overall survival (OS) rates have improved over the years in HIRA data and were reproduced in single-center data. Dividing the patients of single-center data into two periods (2013-2015 [119] vs. 2016-2018 [148]) based on the results of public data, the median OS was significantly different between the two periods (20.9 vs 32.1 months, p=0.003). According to multivariate regression analyses, young age (≤70 years), R0 resection, negative nodal involvement, adjuvant treatment, and palliative chemotherapy with FOLFIRINOX or gemcitabine plus nab-paclitaxel (GNP) were significantly associated with better OS. A survival prediction model was created using the beta-coefficients in cox regression analysis of the above five significant factors, and the c-index by bootstrap validation (resampling, 1500) was 0.7088. The weight scores were as follows: Age >70 years, 1; R1 resection, 1; pN1, 1; pN2 stage, 3; no adjuvant treatment, 2; palliative chemotherapy with FOLFIRINOX and/or GNP, 3; without FOLFIRINOX or GNP, 5; no palliative chemotherapy, 5. Conclusions: Regarding the survival trends in patients with resected PC, we presented the recent improvement in survival over the years and suggested several clinical factors that contributed to it by different weights. Further studies are necessary for validation.[Table: see text]

739 Background: For precision medicine, patient-derived organoid (PDO) is regarded as one of the promising models. However, current PDOs were mainly derived from surgical specimens. We aimed to analyze the single cell RNA-sequencing (scRNA-seq) of PDO from various sampling methods with different pathologic outcomes. Methods: In 2021, three pancreatic cancer and one gallbladder cancer samples were collected from surgical specimen, endoscopic ultrasound guided-fine needle biopsy (EUS-FNB), and endoscopic retrograde cholangiopancreatography (ERCP)-guided biopsy. The samples were mechanically dissociated with dissociation buffer and incubated using shaking incubator. Dissociated cells were seeded into growth factor reduced Matrigel. From these PDOs, we generated scRNA-seq data in each experimental design, and corrected batch effects that could occur when multiple samples are considered simultaneously in downstream analysis. Marker genes representing each cell subcluster were identified, and statistical hypothesis tests were performed to identify genes differentially expressed according to differences in biopsy methods and/or pathological results. Results: We found the optimal 8 types of sub cell-type clusters with a resolution parameter of 0.3 in clustering analysis based on the Uniform Manifold Approximation and Projection (UMAP) algorithm in terms of silhouette score. As a result of examining the expression levels of KRT19, a marker gene for malignant ductal cells, and RGS5, a stellate marker gene, which showed the same pattern as the existing PDAC transcriptome studies, it was confirmed that most of the cells derived from PDOs were malignant ductal cells. Finally, we identified a heterogeneous effect on gene expression patterns in ductal cells depending on not only pathological positivity, but also biopsy methods for organoid. Conclusions: According to our scRNA-seq, most cells were malignant cells and EUS-FNB could be a good sampling method for PDOs. However, further analysis about a heterogeneous effect on gene expression patterns is necessary.[Table: see text]

The survival rate of patients with cancer has been increasing because of the sustained anticancer effect of new drugs, such as immune checkpoints inhibitors (ICI). Unlike the existing cytotoxic chemotherapies, immunotherapy causes immune system disturbance, such as hypothyroidism. Comparative studies on hypothyroidism following administration of ICI alone and in combination with other drugs are scarce. Therefore, we investigated the incidence of hypothyroidism after ICI in patients with cancer using a national population-based database.Using the claims data from the Health Insurance Review and Assessment service in Korea, we retrospectively investigated patients with cancer who received chemotherapy between January 1, 2014 and February 28, 2021.Of all patients with cancer (n = 665,445) who received all kinds of chemotherapy, those who have received ICI accounted for 1.91 %. Compare with cytotoxic chemotherapy and angiogenesis inhibitors (AIs), ICI was associated with earlier (236.1 ± 248.4 vs. 811.1 ± 661.7, P 0.01) and more frequent (7.7 % vs. 4.4 %, P 0.01) occurrence of hypothyroidism, as well as an increased risk of developing hypothyroidism (odds ratio [OR] 1.69, 95 % confidence interval [CI] 1.58-1.80). However, the incidence of grade 2 or higher hypothyroidism was similar in both groups of patients who received ICI (3.3 %) and AI (3.1 %). The incidence of hypothyroidism was 4.4 times higher in patients who received both AI and ICI than in those who were treated with ICI alone (OR 4.41, 95 % CI 3.40-5.71).This study showed a synergistic effect in patients who received multiple administrations of a drug that might be associated with thyroid dysfunction. Therefore, special attention should be paid to the treatment-related side effects when using drugs, such as AIs, concomitant with ICI treatment.

PurposeWe investigated the intensive care unit (ICU) outcomes of patients who used targeted therapy compared to those who received cytotoxic chemotherapy.Materials and MethodsThis study was based on Korean administrative health insurance claims from 2015 to 2019. We extracted data on lung cancer patients (>18 years old) who were admitted to the ICU after receiving chemotherapy.Results6,930 lung cancer patients who received chemotherapy within 30 days before ICU admission were identified; the patients received cytotoxic chemotherapy (85.4%, n = 5,919) and molecular targeted therapy (14.5%, n = 1,011). Grade 4 neutropenia was identified only in the cytotoxic chemotherapy group (0.6%). Respiratory failure requiring ventilator treatment was more common in the cytotoxic chemotherapy group than in the targeted therapy group (HR, 3.30; 95% CI, 2.99–3.63), and renal failure requiring renal replacement therapy was not significantly different between the two groups (HR, 1.57; 95% CI, 1.36–1.80). Patients who received targeted chemotherapy stayed longer in the ICU than the cytotoxic chemotherapy. The 28-day mortality was 23.4% (HR, 0.79; 95% CI, 0.67–0.90, p < 0.05) among patients who received targeted agents compared with 29.6% among patients who received cytotoxic chemotherapy.ConclusionTargeted chemotherapy for lung cancer may contribute to increasing access to critical care for lung cancer patients, which may play a role in improving critical care outcomes of lung cancer patients.

Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data.Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea.The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018.The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P –8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P –6) associated with emphysema in all subjects, and 106 SNPs (P –6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

BackgroundUntil recently, studies on long-term outcomes of critically ill patients with cancer have been mainly restricted to specific subgroups of patients. The aim of this study was to evaluate the long-term (5 years) clinical outcomes of patients who received intensive care unit (ICU) treatment using the Korean nationwide data.MethodsAll patients aged >18 years with ICU admission, according to the claims data from the Health Insurance Review and Assessment Service from January 2008 to December 2010, were enrolled. The enrolled patients were followed up until December 2015. We analyzed clinical outcomes, including mortality after admission to the ICU. Critically ill patients were categorized into four subgroups: patients without cancer; with solid cancer except lung; with lung cancer; and with hematologic malignancies.ResultsAmong all critically ill patients admitted to the ICU (n = 323,765), the proportion of patients with cancer continued to increase from 21.5% in 2008 to 27.8% in 2010. Critically ill patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p < 0.001). There was no difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer which was not lung cancer or hematologic malignancies (14.3%, p = 0.28). Hazard ratios for the ICU mortality at 5 years were: 1.90 (95% confidence interval [CI]: 1.87–1.94) for lung cancer; 1.44 (95% CI: 1.43–1.46) for other solid cancers; and 3.05 (95% CI: 2.95–3.16) for hematologic malignancies, versus patients without cancer.Conclusion The results of this study suggest that, in the short term, the outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for cases with lung cancer and hematologic malignancies. However, the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients.

BACKGROUND: Recent advances in critical care and infection control have led to improved intensive care unit (ICU) survival rates. However, controversy exists regarding the benefits of ICU treatment for patients with lung cancer. In this study, we evaluated the clinical outcomes of patients from the Korean national database, who had been diagnosed with lung cancer and had received ICU treatment. METHODS: We investigated patients in Korea who had been newly diagnosed with lung cancer between January 1, 2008 and December 31, 2010. We classified these critically ill patients with lung cancer according to their lung cancer treatment pathways, with a specific focus on those who had undergone ICU treatment. RESULTS: We found that 31.3% of patients newly diagnosed with lung cancer had been admitted to the ICU for any reason, and 18.5% of patients with lung cancer were admitted to the ICU for reasons other than postoperative surgical lung cancer resection. The ICU mortality rate was 2.9% in patients admitted to the ICU for postoperative care and 47.5% in patients admitted for other reasons. Clinical cancer staging (HR, 7.02; 95% CI, 5.82–8.48; P

We aimed to evaluate the long-term use or effects of domiciliary non-invasive positive pressure ventilation (NIPPV) used to treat patients with chronic obstructive pulmonary disease (COPD). Databases were searched to identify randomized controlled trials (RCTs) of COPD with NIPPV for longer than 1 year. The primary outcome as mortality rates were accessed in this meta-analysis. The eight trials included in this study comprised data from 913 patients. The mortality rates for the NIPPV and control groups were 29% (118/414) and 36% (151/419); this difference was statistically significant (risk ratio (RR): 0.79, 95% confidence interval (CI): 0.65-0.95). Mortality rates were reduced with NIPPV in four trials that included stable COPD patients. There was no difference in admission, acute exacerbation and quality of life (QOL) between the NIPPV and control groups. There was no significant difference in withdrawal rates between the two groups (RR 0.99, 95% CI 0.72-1.36, p = 0.94). Maintaining long-term nocturnal NIPPV for more than 1 year in COPD patients, especially stable status COPD patients, leads to a decrease in the mortality rate, and the withdrawal rate is not high compared to long term oxygen treatments.

Although several studies have reported outcome data on critically ill children, detailed reports by age are not available. We aimed to evaluate the age-specific estimates of trends in causes of diagnosis, procedures, and outcomes of pediatric admissions to ICUs in a national representative sample.A population-based retrospective cohort study.Three hundred forty-four hospitals in South Korea.All pediatric admissions to ICUs in Korea from August 1, 2009, to September 30, 2014, were covered by the Korean National Health Insurance Corporation, with virtually complete coverage of the pediatric population in Korea. Patients less than 18 years with at least one ICUs admission between August 1, 2009, and September 30, 2014. We excluded neonatal admissions (28 days), neonatal ICUs, and admissions for health status other than a disease or injury. The final sample size was 38,684 admissions from 32,443 pediatric patients.None.The overall age-standardized admission rate for pediatric patients was 75.9 admissions per 100,000 person-years. The most common primary diagnosis of admissions was congenital malformation (10,897 admissions, 28.2%), with marked differences by age at admission (5,712 admissions [54.8%] in infants, 3,994 admissions [24.6%] in children, and 1,191 admissions [9.9%] in adolescents). Injury was the most common primary diagnosis in adolescents (3,248 admissions, 27.1%). The overall in-hospital mortality was 2,234 (5.8%) with relatively minor variations across age. Neoplasms and circulatory and neurologic diseases had both high frequency of admissions and high in-hospital mortality.Admission patterns, diagnosis, management, and outcomes of pediatric patients admitted to ICUs varied by age groups. Strategies to improve critical care qualities of pediatric patients need to be based on the differences of age and may need to be targeted at specific age groups.

Background The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. Methods Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. Results Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. Conclusions For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.

During the 2015 Korean MERS outbreak, we experienced atypical presentations of MERS-CoV infections in three immunocompromised hosts that warranted exceptional management. Case 1 showed delayed symptom development after a four-day asymptomatic period, Case 2 experienced a 20-day incubation period, and Case 3 exhibited persistent viral shedding without clinical deterioration. Recognizing these exceptions is extremely important in the management of MERS-CoV-exposed or -infected patients and for control of potential MERS outbreaks.

This study aimed to investigate cognitive impairment and psychological distress of critically ill patients at discharge from intensive care unit (ICU). This study included 30 critically ill patients who had neither pre-existing dementia nor ongoing delirium. At ICU discharge, they performed a screening test for cognitive impairment (Mini-Cog test) and completed questionnaires for depression (Patient Health Questionnaire-2, PHQ-2) and for 4 stressful experiences during ICU stay including nightmares, severe anxiety or panic, severe pain, and trouble to breathe or feeling of suffocation (Post-Traumatic Stress Syndrome 14-Question Inventory, PTSS-14 Part A). Thirteen patients (43.3%) screened positive for cognitive impairment and 18 patients (60.0%) exhibited depressive symptoms. Twenty three patients (76.7%) recollected one or more stressful in-ICU experiences. Female patients (88.9%) was more likely to feel depressed at ICU discharge, compared to male patients (47.6%) (χ2=4.47, p=0.03). To the best of our knowledge, this is the first report on cognitive and psychological outcomes of ICU survivors in Korea. In this study, we observed that a considerable number of critically ill patients had experienced cognitive impairment or psychological distress at ICU discharge.

This study was performed to evaluate the potential association between serum heavy metal levels and lung function in a cohort of chronic obstructive pulmonary disease (COPD) patients. We analyzed data from 152 subjects enrolled in a cohort study on COPD from 2012 to 2013 and living in a dusty area. In total, 152 subjects from the cohort study were enrolled; 111 were diagnosed with OLD. There was a significant association between post-bronchodilator FEV1 and serum mercury level after adjusting for age, gender and smoking status (p=0.03). Following the adjustment, a significantly higher prevalence of OLD was observed in subjects in the highest mercury concentration tertile (p=0.03). The risk of OLD was significantly higher for subjects in the higher mercury concentration (odds ratio, 3.62; 95% confidence interval: 1.29-10.18) than in those in the lowest tertile. In conclusion, serum mercury level may be a risk factor for reduced lung function and OLD.

Background Despite the increasing importance of rehabilitation for critically ill patients, there is little information regarding how rehabilitation therapy is utilized in clinical practice. Our objectives were to evaluate the implementation rate of rehabilitation therapy in the intensive care unit (ICU) survivors and to investigate the effects of rehabilitation therapy on outcomes. Methods A retrospective nationwide cohort study with including > 18 years of ages admitted to ICU between January 2008 and May 2015 (n = 1,465,776). The analyzed outcomes were readmission to ICU readmission and emergency room (ER) visit. Results During the study period, 249,918 (17.1%) patients received rehabilitation therapy. The percentage of patients receiving any rehabilitation therapy increased annually from 14% in 2008 to 20% in 2014, and the percentages for each type of therapy also increased over time. The most common type of rehabilitation was physical therapy (91.9%), followed by neuromuscular electrical stimulation (29.6%), occupational (28.6%), respiratory, (11.6%) and swallowing (10.3%) therapies. After adjusting for confounding variables, the risk of 30-day ICU readmission was lower in patients who received rehabilitation therapy than in those who did not (P < 0.001; hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.65–0.75). And, the risk of 30-day ER visit was also lower in patients who received rehabilitation therapy (P < 0.001; HR, 0.83; 95% CI, 0.77–0.88). Conclusion In this nationwide cohort study in Korea, only 17% of all ICU patients received rehabilitation therapy. However, rehabilitation is associated with a significant reduction in the risk of 30-day ICU readmission and ER visit., Graphical Abstract

BACKGROUND: Multiple studies have identified COPD subtypes by using visual or quantitative evaluation of CT images. However, there has been no systematic assessment of a combined visual and quantitative CT imaging classification. We integrated visually defined patterns of emphysema with quantitative imaging features and spirometry data to produce a set of 10 nonoverlapping CT imaging subtypes, and we assessed differences between subtypes in demographic features, physiological characteristics, longitudinal disease progression, and mortality. METHODS: We evaluated 9,080 current and former smokers in the COPDGene study who had available volumetric inspiratory and expiratory CT images obtained using a standardized imaging protocol. We defined 10 discrete, nonoverlapping CT imaging subtypes: no CT imaging abnormality, paraseptal emphysema (PSE), bronchial disease, small airway disease, mild emphysema, upper lobe predominant centrilobular emphysema (CLE), lower lobe predominant CLE, diffuse CLE, visual without quantitative emphysema, and quantitative without visual emphysema. Baseline and 5-year longitudinal characteristics and mortality were compared across these CT imaging subtypes. RESULTS: The overall mortality differed significantly between groups (P < .01) and was highest in the 3 moderate to severe CLE groups. Subjects having quantitative but not visual emphysema and subjects with visual but not quantitative emphysema were unique groups with mild COPD, at risk for progression, and with likely different underlying mechanisms. Subjects with PSE and/or moderate to severe CLE had substantial progression of emphysema over 5 years compared with findings in subjects with no CT imaging abnormality (P < .01). CONCLUSIONS: The combination of visual and quantitative CT imaging features reflects different underlying pathological processes in the heterogeneous COPD syndrome and provides a useful approach to reclassify types of COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76-1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69-1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings.

Background The feasibility of liver transplantation (LT) in elderly recipients remains a topic of debate. Methods This cohort study evaluated the impact of recipient's age on LT outcome between January 2007 and May 2016 covered by the Korean National Health Insurance system (n = 9415). Multilevel regression models were used to determine the impact of recipient's age on in-hospital and long-term mortality after LT. Results All patients had a first LT, with 2473 transplanted with liver from deceased donors (DD) and 6942 from living donors. The mean age was 52.2 ± 9.0 years. Most LT were performed on patients in their 50s (n = 4290, 45.6%) and 0.9% (n = 84) of the LT was performed on patients older 70 years. The overall in-hospital mortality was 6.3%, and the 3-year mortality was 11.3%. The in-hospital mortality included, 13.5% associated with DDLT and 3.7% involved living donor LT. When compared with that for patients aged 51 to 55 years, the risk of death among recipients older than 70 years was about fourfold higher after adjusting for baseline liver disease (odds ratio, 4.1; 95% confidence interval, 2.21-7.58), and was nearly threefold higher after adjusting for baseline liver disease and perioperative complications (odds ratio, 2.92; 95% confidence interval, 1.37-6.24). Also, the cost of LT increased significantly with age. Conclusions The data show that age remains an important risk factor for LT, suggesting that LT should be considered with caution in elderly recipients., The authors examined mortality risk for a large cohort of liver transplant recipients between 2007 and May 2016 covered by the Korean National Health Insurance system (n = 9415). Both costs and mortality were significantly increased in the cohort over 70 years old. Supplemental digital content is available in the text.

ECMO use has increased lately. However, differences between adult ECMO and non-ECMO patients admitted to the ICU remain unstudied. In terms of volume-outcome relationship, the impact of ECMO volume on survival has not been validated in a real world cohort.Retrospective analysis of data from the Korean Health Insurance Review and Assessment Service over 5 years, between August 1, 2009 and July 31, 2014. The ECMO group comprised patients who received ≥1 ECMO run. Data on patient demographics, ICU and hospital length of stay, cost, treatments, and in-hospital mortality were collected. Usage trends were analyzed by 5 one-year periods.Among 1, 265, 508 ICU patients, 6078 underwent ECMO during the study period. The number of ECMO patients rose by 2.5 times, and ECMO hospitals from 50 to 86 between periods 1 and 5. Compared to non-ECMO patients, the ECMO group was younger (59 years vs. 64 years, p .0001) with more comorbidities. Healthcare expenditure and in-hospital mortality in the ECMO group were higher (US $23,600 vs. $5100; 63.4% vs. 12.6%; p .0001). Using multivariable analysis, age ≥ 50 years, CRRT, and annual hospital ECMO volume 20 negatively impacted survival to discharge.The prevalence of ECMO among ICU patients was 0.5%. The expenditure and in-hospital mortality of the ECMO group were four and five times higher than non-ECMO group respectively. An annual hospital ECMO volume ≥ 20 may improve survival to hospital discharge.

The long-term prognosis of vasospastic angina (VSA) patients presenting with aborted sudden cardiac death (ASCD) is still unknown. We sought to compare the long-term clinical outcomes between VSA patients presenting with and without ASCD by retrospective analysis of a nationwide population-based database.A total of 6972 patients in the Health Insurance Review and Assessment database who were hospitalized in the intensive care unit with VSA between July 1, 2007 and May 31, 2015 were enrolled. Primary outcome was the composite of cardiac arrest and acute myocardial infarction after discharge.Five hundred ninety-eight (8.6%) VSA patients presented with ASCD. On inverse probability of treatment weighting, ASCD patients had a significantly increased risk of the composite of cardiac arrest and acute myocardial infarction (adjusted hazard ratio, 2.52; 95% confidence interval, 1.72-3.67; p 0.001) during the median follow-up duration of 4 years. The association of ASCD presentation with a worse outcome in terms of primary outcome was consistent across various subgroups, including comorbidity type and use of vasodilators (all p-values for interaction: non-significant). ASCD patients treated with an implantable cardioverter defibrillator (ICD) had a lower incidence of the composite of cardiac arrest and acute myocardial infarction during follow-up than those without an ICD (p = 0.009).VSA patients that present with ASCD are at increased risk of cardiac arrest or myocardial infarction during long-term follow-up despite adequate vasodilator therapy. An ICD is a potential therapeutic option for secondary prevention.

Background Acute respiratory distress syndrome (ARDS) is potentially underrecognized by clinicians. Early recognition and subsequent optimal treatment of patients with ARDS may be facilitated by usage of biomarkers. Surfactant protein D (SP-D), a marker of alveolar epithelial injury, has been proposed as a potentially useful biomarker for diagnosis of ARDS in a few studies. We tried to validate the performance of plasma SP-D levels for diagnosis of ARDS. Methods We conducted a retrospective analysis using data from three (two in USA and one in Korea) prospective biobank cohorts involving 407 critically ill patients admitted to medical intensive care unit (ICU). A propensity score matched analysis (patients with versus without ARDS, matched 1:1) was carried out using significant variables from multiple logistic regression. The diagnostic accuracy of plasma SP-D as a diagnostic marker of ARDS was assessed by receiver operating characteristic curve analysis. Results Out of the 407 subjects included in this study, 39 (10%) patients fulfilled ARDS criteria. Patients with ARDS had higher SP-D levels in plasma (p

Background: Asian dust is known to have harmful effects on the respiratory system. Respiratory conditions are also influenced by environmental conditions regardless of the presence of pollutants. The same pollutant can have different effects on the airway when the air is dry compared with when it is humid. We investigated hospital visits for chronic obstructive pulmonary disease (COPD) and asthma in relation to the environmental conditions. Methods: We conducted a retrospective study using the Korean National Health Insurance Service claims database of patients who visited hospitals in Chuncheon between January 2006 and April 2012. Asian dust, haze, mist, and fog days were determined using reports from the Korea Meteorological Administration. Hospital visits for asthma or COPD on the index days were compared with the comparison days. We used two-way case-crossover techniques with one to two matching. Results: The mean hospital visits for asthma and COPD were 59.37 ± 34.01 and 10.04 ± 6.18 per day, respectively. Hospital visits for asthma significantly increased at lag0 and lag1 for Asian dust (relative risk [RR], 1.10; 95% confidence interval [CI], 1.01-1.19; p

Introduction: Although occupational exposure is an important risk factor for development of chronic obstructive pulmonary disease (COPD), it has been little known about the effects of occupations exposures for progression of COPD. Aims and Objectives: To determine the effect of history for occupational exposures on lung function decline in men with COPD. Methods: Subjects were selected from a Korean COPD cohort, prospectively designed observational study and underwent yearly post bronchodilator spirometry. They were included if they underwent the spirometry at least three times. History of occupational exposures was evaluated for metal, asbestos, fiber, cereal, drugs, paper dust, and chemicals. History of occupational exposures was assessed by two blinded experts for each case. The annual decline of FEV1 was analyzed by random-slope and random-intercept mixed linear regression. Results: A total 222 patients with COPD were included, and patients with occupational exposures were 49. The mean age was 65.2 (standard deviation: 7.5) years, the mean smoking amount was 46.3 (28.1) pack-years. There were no significant differences in years of age, smoking amount, quality of life, and emphysema extent on CT, according to the presence of occupation exposures. The annual decline rates in FEV1 (ml per year) were significantly different for groups without occupational exposures of -32.9±21.9 compared to groups with occupational exposures of -25.5±19.9 (p = 0.038). Conclusions: Occupational exposures in men with COPD were associated with slower decline of lung function.