Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.