Tuberculous pleural effusion-induced Arg-1+ macrophage polarization contributes to lung cancer progression via autophagy signaling.

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

Gender Differences in Antitussive Prescriptions for Chronic Cough in Korea.

Background: We investigated the differences in the characteristics and prognoses between the sexes of patients with chronic cough who were prescribed antitussive agents, using a Korean population-based database. Methods: Claims data from South Korea's Health Insurance Review and Assessment (HIRA) service were analyzed. This retrospective observational cohort study considered chronic cough patients aged 18 years and older who were consistently prescribed antitussive agents for more than 2 months between 1 January 2017 and 30 June 2019. Results: Among the 207,989 patients treated for chronic cough, the prevalence of unexplained cough was higher in women (men: 6.2% vs. women: 9.7%) and the prevalence of persistent cough was higher in men (men: 16.8% vs. women: 14.3%). The gap in the proportion of COPD, lung cancer, ILD, GERD, and TB between women and men were largest around the age range of 60-70 years. With the exception of those in their 60s and 70s, women were more likely to have chronic cough and persistent cough than men. Women were more likely to discontinue medication after treatment completion than men. Only 53.9% of patients discontinued cough medication for more than 6 months after treatment completion. Within 12 and 18 months, respectively, 8.9% and 11.9% of them revisited the hospital for chronic cough. Via Cox regression analysis, an age in the 60s or 70s and explained cough were independently associated with a higher risk of revisit for treatment. Conclusions: Among patients treated for chronic cough, there were distinct differences in cough characteristics and prescription status between men and women. Our data highlight the need for a new personalized treatment approach to chronic cough, taking into account the gender, age, and underlying diseases of patients. Further research is needed to determine whether appropriate underlying disease control and gender-specific treatment are effective for managing chronic cough.

Association between the Respiratory Microbiome and Plasma Microbial Extracellular Vesicles in Intubated Patients.

Extracellular vesicles (EVs) regulate various cellular and immunological functions in human diseases. There is growing interest in the clinical role of microbial EVs in pneumonia. However, there is a lack of research on the correlation between lung microbiome with microbial EVs and the microbiome of other body sites in pneumonia. We investigated the co-occurrence of lung microbiome and plasma microbe-derived EVs (mEVs) in 111 samples obtained from 60 mechanically ventilated patients (41 pneumonia and 19 non-pneumonia cases). The microbial correlation between the two samples was compared between the pneumonia and non-pneumonia cases. Bacterial composition of the plasma mEVs was distinct from that of the lung microbiome. There was a significantly higher correlation between lung microbiome and plasma mEVs in non-pneumonia individuals compared to pneumonia patients. In particular, Acinetobacter and Lactobacillus genera had high correlation coefficients in non-pneumonia patients. This indicates a beneficial effect of mEVs in modulating host lung immune response through EV component transfer.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

Background: A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. Methods: We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Results: Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Conclusion: Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

Risk for multidrug-resistant tuberculosis in patients treated with anti-tumor necrosis factor agents.

Background: There are few studies on medical conditions associated with the development of drug-resistant TB. Objective: We investigated the risk factors for the occurrence of multidrug-resistant (MDR) tuberculosis (TB) in patients with pulmonary TB. Materials and methods: Based on claims data from the Health Insurance Review and Assessment service in South Korea, we retrospectively investigated patients aged 18 years or older with active pulmonary TB who were treated with anti-TB therapy between January 1, 2008, and February 28, 2021. Results: Among 248,176 patients with pulmonary TB who underwent anti-TB therapy, 2.0% were identified as having MDR-TB. MDR-TB showed male predominance compared to patients without MDR-TB, and patients with MDR-TB were younger. The risk for MDR-TB in patients treated with anti-TB therapy was 3.26 times higher in patients who received anti-tumor necrosis factor (TNF) agents before prescription of anti-TB medications than in those who had never been exposed to anti-TNF agents after adjusting for other TB risk factors (age, sex, inhaled corticosteroid, diabetes mellitus, liver disease, pneumoconiosis, and organ or blood recipients). The risk for MDR-TB was also increased in males and younger patients. Conclusion: Treatment with an anti-TNF agent could be a driver of MDR-TB in patients with pulmonary TB.

Experience and perspectives of end-of-life care discussion and physician orders for life-sustaining treatment of Korea (POLST-K): a cross-sectional study.

BACKGROUND: This study aimed to identify the healthcare providers' experience and perspectives toward end-of-life care decisions focusing on end-of-life discussion and physician's order of life-sustaining treatment documentation in Korea which are major parts of the Life-Sustaining Treatment Act. METHODS: A cross-sectional survey was conducted using a questionnaire developed by the authors. A total of 474 subjects-94 attending physicians, 87 resident physicians, and 293 nurses-participated in the survey, and the data analysis was performed in terms of frequency, percentage, mean and standard deviation using the SPSS 24.0 program. RESULTS: Study results showed that respondents were aware of terminal illness and physician's order of life-sustaining treatment in Korea well enough except for some details. Physicians reported uncertainty in terminal state diagnosis and disease trajectory as the most challenging. Study participants regarded factors (related to relationships and communications) on the healthcare providers' side as the major impediment to end-of-life discussion. Study respondents suggested that simplification of the process and more staff are required to facilitate end-of-life discussion and documentation. CONCLUSION: Based on the study results, adequate education and training for better end-of-life discussion are required for future practice. Also, a simple and clear procedure for completing a physician's order of life-sustaining treatment in Korea should be prepared and legal and ethical advice would be required. Since the enactment of the Life-Sustaining Treatment Act, several revisions already have been made including disease categories, thus continuous education to update and support clinicians is also called for.

The prognosis of non-small cell lung cancer patients according to endobronchial metastatic lesion.

To evaluate the prognosis of non-small cell lung cancer (NSCLC) patients according to endobronchial metastatic lesion (EML), especially those not identified on positron emission tomography or computed tomography. We evaluated progression-free survival (PFS) and overall survival (OS) according to the presence of EML in patients with NSCLC who were diagnosed at a tertiary hospital between January 2010 and December 2019. A total of 364 patients were enrolled in this study. EML was found in 69 (19.0%) patients with NSCLC. In the patients with EML versus the patients without EML, median PFS was 7.0 (3.5-13.5) and 9.5 (5.5-17.5) months (P = 0.011), and median OS was 12.0 (6.0-30.0) versus 20.0 (10.0-39.0) months (P = 0.016), respectively. Median PFS and OS rates were highest in epidermal growth factor receptor (EGFR) (+) and EML (-) patients and lowest in EGFR (-) and EML (+) patients (P < 0.001). By multivariate cox regression analysis, PFS in overall patients with NSCLC was significantly associated with EML, EGFR mutation, performance status, and pleural effusion. NSCLC patients with EML had worse prognoses of PFS and OS than patients without EML.

Metagenomic Analysis of Plasma Microbial Extracellular Vesicles in Patients Receiving Mechanical Ventilation: A Pilot Study.

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 ß 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 ß 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.

Differences in ICU Outcomes According to the Type of Anticancer Drug in Lung Cancer Patients.

PURPOSE: We investigated the intensive care unit (ICU) outcomes of patients who used targeted therapy compared to those who received cytotoxic chemotherapy. MATERIALS AND METHODS: This 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. RESULTS: 6,930 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. CONCLUSION: Targeted 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.

Analysis of treatment pattern of anti-dementia medications in newly diagnosed Alzheimer's dementia using OMOP CDM.

Anti-dementia medications are widely prescribed to patients with Alzheimer's dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format-the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009-2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-D-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

A Comprehensive Analysis of 5-Year Outcomes in Patients with Cancer Admitted to Intensive Care Units.

BACKGROUND: The aim of this study was to evaluate the long-term (5-year) clinical outcomes of patients who received intensive care unit (ICU) treatment using Korean nationwide data. METHODS: All patients aged -gt;18 years with ICU admission according to Korean claims data from January 2008 to December 2010 were enrolled. These enrolled patients were followed up until December 2015. The primary outcome was ICU mortality. RESULTS: Among all critically ill patients admitted to the ICU (n=323,765), patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p-lt;0.001). However, there was no significant difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer (lung cancer or hematologic malignancies) (14.3%). Compared to patients without cancer, hazard ratios of those with cancer for ICU mortality at 5 years were: 1.90 (1.87-1.94) for lung cancer; 1.44 (1.43-1.46) for other solid cancers; and 3.05 (2.95-3.16) for hematologic malignancies. CONCLUSION: This study showed that the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients. However, short term outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for those with lung cancer or hematologic malignancies.

Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD. Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. METHODS: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. RESULTS: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219, P = 0.015). CONCLUSION: Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

DNA Methylation Markers in Lung Cancer.

Lung cancer is the most common cancer and the leading cause of cancer-related morbidity and mortality worldwide. As early symptoms of lung cancer are minimal and non-specific, many patients are diagnosed at an advanced stage. Despite a concerted effort to diagnose lung cancer early, no biomarkers that can be used for lung cancer screening and prognosis prediction have been established so far. As global DNA demethylation and gene-specific promoter DNA methylation are present in lung cancer, DNA methylation biomarkers have become a major area of research as potential alternative diagnostic methods to detect lung cancer at an early stage. This review summarizes the emerging DNA methylation changes in lung cancer tumorigenesis, focusing on biomarkers for early detection and their potential clinical applications in lung cancer.

Clinical outcomes in patients with lung cancer admitted to intensive care units.

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<0.01) and the need for mechanical ventilator (HR, 1.34; 95% CI, 1.27-1.41; P<0.01) were independently associated with ICU mortality. The importance of mechanical ventilator intervention as a predictor for survival was significantly greater in the earlier stages of lung cancer (HR, 1.97; 95% CI, 1.15-3.38; P<0.01). CONCLUSIONS: This study suggests that goals and treatment plans for critically ill patients with lung cancer should be determined by the individual patient's clinical cancer stage, regardless of the reason for admission to the ICU.

Effect of Electric Field Distribution on the Heating Uniformity of a Model Ready-to-Eat Meal in Microwave-Assisted Thermal Sterilization Using the FDTD Method.

Microwave assisted thermal sterilization (MATS) is a novel microwave technology currently used in the commercial production of ready-to-eat meals. It combines surface heating of high-temperature circulation water with internal microwave heating in cavities. The heating pattern inside the food packages in a MATS process depends heavily on the electric field distribution formed by microwaves from the top and bottom windows of the microwave heating cavities. The purpose of this research was to study the effect of the electric field on 922 MHz microwave heating of ready-to-eat meals as they moved through the microwave chamber of a pilot-scale MATS system using the finite-difference time-domain (FDTD) method. A three-dimensional numerical simulation model was developed as a digital twin of the MATS process of food moving through the microwave chamber. The simulation showed that the electric field intensity of the MATS microwave cavity was greatest on the surface and side edge of the cavity and of the food. There was a strong similarity of the experimental heating pattern with that of the electric field distribution simulated by a computer model. The digital twin modeling approach can be used to design options for improving the heating uniformity and throughput of ready-to-eat meals in MATS industrial systems.

Active Treatment Improves Overall Survival in Extremely Older Non-Small Cell Lung Cancer Patients: A Multicenter Retrospective Cohort Study.

PURPOSE: As the aging of society progresses, the proportion of extremely older lung cancer patients has also increased; However, studies of these patients with non-small cell lung cancer are limited. Therefore, we investigated the initial treatment modalities and survival outcomes for patients aged 80 years or over. MATERIALS AND METHODS: We included a multicenter retrospective cohort from the Korean Association for Lung Cancer Registry, which surveys 10% of the newly diagnosed lung cancer patients across 52 hospitals in Korea. We analyzed and compared the 2014-2016 data of the non-small cell lung cancer patients aged ≥ 80 years and those aged < 80 years. RESULTS: Of the 6,576 patients reviewed, 780 patients were aged ≥ 80 years, and 5,796 patients were aged < 80 years. In the patients aged ≥ 80 years, surgery and radiation therapy resulted in longer patient survival among those with a resectable tumor (stage I-II) than the best supportive care (median survival, not reached [surgery] vs. 32.2 months [radiation therapy] vs. 11.43 months [best supportive care]). The duration of survival in patients with advanced-stage (IV) lung cancers was higher after chemotherapy than after the best supportive care (median survival, 8.63 months vs. 2.5 months). Patients with stage IV adenocarcinoma who received targeted therapy had better survival than those who did not (median survival, 9.0 months vs. 4.3 months). CONCLUSION: Even in extremely older patients, active treatments, such as surgery, radiation therapy, and chemotherapy, can result in better survival outcomes than the best supportive care.

Tuberculosis-Infected Giant Bulla Treated by Percutaneous Drainage Followed by Obliteration of the Pulmonary Cavity Using Talc: Case Report.

Tuberculosis (TB)-infected giant bullae are rare. A 55-year-old man was referred when an infected bulla did not respond to empirical treatment. Computed tomography showed a giant bulla in the right upper lobe with an air-fluid level and surrounding infiltrate. Sputum culture, acid-fast bacilli (AFB) stain, and polymerase chain reaction (PCR) for TB were negative. Percutaneous drainage of the bullous fluid was performed. AFB stain and PCR were positive in the drained fluid. The patient was given anti-TB drugs and later underwent obliteration of the pulmonary cavity using talc. To summarize, we report a patient with a TB-infected giant bulla that was treated successfully with anti-TB drugs and obliteration of the pulmonary cavity using talc.

Difference of copy number variation in blood of patients with lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Copy number variation (CNV) in several genetic regions correlate with cancer susceptibility. Hence, this study evaluated the association between CNV and non-small cell lung cancer (NSCLC) in the peripheral blood. METHODS: Blood samples of 150 patients with NSCLC and 150 normal controls were obtained from a bioresource center (Seoul, Korea). Through an epigenome-wide analysis using the MethylationEPIC BeadChip method, we extracted CNVs by using an SVS8 software-supplied multivariate method. We compared CNV frequencies between the NSCLC and controls, and then performed stratification analyses according to smoking status. RESULTS: We acquired 979 CNVs, with 582 and 967 copy-number gains and losses, respectively. We identified five nominally significant associations (ACOT1, NAA60, GSDMD, HLA-DPA1, and SLC35B3 genes). Among the current smokers, the NSCLC group had more CNV losses and gains at the GSDMD gene in chromosome 8 (P=0.02) and at the ACOT1 gene in chromosome 14 (P=0.03) than the control group. It also had more CNV losses at the NAA60 gene in chromosome 16 (P=0.03) among non-smokers. In the NSCLC group, current smokers had more CNV gains and losses at the ACOT1 gene in chromosome 14 (P=0.003) and at HLA-DPA1 gene in chromosome 6 (P=0.02), respectively, than non-smokers. CONCLUSION: Five nominally significant associations were found between the NSCLC and CNVs. CNVs are associated with the mechanism of lung cancer development. However, the role of CNVs in lung cancer development needs further investigation.

Plasma concentrations of NOX4 are predictive of successful liberation from mechanical ventilation and 28-day mortality in intubated patients.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzymes play important roles in generating reactive oxygen species (ROS); in particular, NOX4 plays a distinct role in regulating lung inflammation and apoptosis. METHODS: We determined whether plasma NOX4 level can be used as a prognostic biomarker to guide weaning from mechanical ventilation and to predict mortality in intubated patients. Plasma levels of NOX4 were measured at days 1 (NOX4 D1) and 7 (NOX4 D7) after initiation of mechanical ventilation in 184 patients. RESULTS: With increase in day 7 NOX4 quartile, the success of weaning tended to decrease and 28-day mortality tended to increase. On multivariate logistic regression, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) [odds ratio (OR): 1.10; 95% CI, 1.02-1.18], duration of mechanical ventilation (OR: 1.12; 95% CI: 1.06-1.18), and NOX4 D7 levels >18.2 ng/mL (OR: 4.40; 95% CI: 1.91-10.06) were independently associated with weaning failure. Also, Cox-hazard proportional model showed that NOX4 D7 level >18.2 ng/mL (hazard ratio [HR], 2.29; 95% CI, 1.26-4.16), APACHE II (HR: 1.07; 95% CI: 1.02-1.14), Sequential Organ Failure Assessment (SOFA) (HR: 1.10; 95% CI: 1.01-1.20) and coexisting cancer (HR: 1.99; 95% CI, 1.01-3.94), were independently associated with 28-day mortality. The longitudinal trend of NOX4 level varied according to the clinical outcomes. CONCLUSIONS: An increased plasma NOX4 D7 level was associated with weaning failure and 28-day mortality in patients with mechanical ventilation. Our results suggest that NOX4-directed management may lead to improved outcomes in patients with mechanical ventilation.

Epigenome-Wide Association Analysis of Differentially Methylated Signals in Blood Samples of Patients with Non-Small-Cell Lung Cancer.

Lung cancer is a common form of cancer and the leading cause of cancer-related deaths worldwide. Early diagnosis using noninvasive biomarkers may play an important role in increasing the survival rate of patients with lung cancer. Biomarkers of DNA methylation in blood samples may improve the early diagnosis of lung cancer. Here, we used peripheral blood samples obtained from 150 patients diagnosed with non-small-cell lung cancer (NSCLC) and 150 healthy controls. The latter were selected by frequency matching with the 150 patients with NSCLC, based on age, sex, and smoking status. Genome-wide methylation profiles were obtained using a MethylationEPIC BeadChip Kit, which covers the 850k bp cytosine-phosphate-guanine site. This analysis showed two significant differentially methylated changes (cg12169243 [DPH6] and cg25429010 [IMP3]) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [USP7], cg06366994 [CPE], cg24992236 [MEG9], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [RSL24D1], cg04989085 [FAM113B], cg20905681 [CKAP4], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC. The validation of these DNA methylation changes and further research on the related genes may help develop easily accessible biomarkers for the early diagnosis or prognosis of NSCLC.