Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

A significant portion of newly diagnosed lung cancer cases occurs in populations exposed to air pollution. The World Health Organization has identified air pollution as a human carcinogen, prompting many countries to implement monitoring systems for ambient particulate matter (PM). PM is composed of a complex mixture of organic and inorganic particles, both solid and liquid, that are found in the air. Given the carcinogenic properties of PM and the high prevalence of lung cancer among exposed populations, exploring their connection and clinical implications is critical for effectively preventing lung cancer in this group. This review explores the relationship between ambient PM and lung cancer. Epidemiological studies have demonstrated a dose-response relationship between PM exposure and lung cancer risk. PM exposure induces oxidative stress, disrupts the body’s redox balance, and causes DNA damage, which is a crucial factor in cancer development. Recent findings on the strong correlation between ambient PM and adenocarcinoma highlight the importance of understanding the specific molecular and pathological mechanisms underlying pollution-related lung cancer. In addition to efforts to control emission sources at the international level, a more individualized approach is essential for preventing PM-related lung cancer.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background: Frozen shoulder (FS) is often accompanied by a rotator cuff tear (RCT), but it can be challenging to diagnose a concomitant RCT without imaging studies. Therefore, having practical criteria to identify patients requiring imaging studies at initial presentation with FS would lead to more cost-effective use of these studies. This study investigated the relationship between RCT and stiffness in patients with FS and whether this relationship was modified by patient age. Methods: This study included 540 adults with shoulder pain who had ≥ 10° of limited passive range of motion in forward flexion, compared to the contralateral side. Patients were categorized into 2 groups depending on the degree of forward flexion stiffness: overhead stiffness (OHS) group, patients with ≥ 110° forward flexion (n = 349); and non-OHS group, patients with forward flexion < 110° (n = 191). The presence of concomitant RCT was determined by magnetic resonance imaging and compared between groups before and after stratification by age. Results: The OHS group had increased odds of concomitant RCT, compared to the non-OHS group (odds ratio [OR], 4.99; 95% CI, 3.36–7.42). OHS was also significantly associated with a more severe grade of RCT (no tear, partial-thickness tear, or full-thickness tear) (OR, 4.42; 95% CI, 3.05–6.39). The odds of RCT in the OHS group, compared to the non-OHS group, increased with age (50–59 years: OR, 3.83; 95% CI, 1.96–7.48; 60–69 years: OR, 5.94; 95% CI, 3.14–11.26; and 70–79 years: OR, 7.67; 95% CI, 2.71–21.66). Conclusions Patients with FS and forward flexion range of motion ≥ 110° (i.e., OHS) at initial presentation had approximately 5-fold higher odds of concurrent RCT than patients with non-OHS. Moreover, in patients aged 50 years or above, these odds increased up to almost 8-fold. Therefore, we recommend confirming the rotator cuff integrity with magnetic resonance imaging in patients with FS and OHS.

Background: Frozen shoulder (FS) is often accompanied by a rotator cuff tear (RCT), but it can be challenging to diagnose a concomitant RCT without imaging studies. Therefore, having practical criteria to identify patients requiring imaging studies at initial presentation with FS would lead to more cost-effective use of these studies. This study investigated the relationship between RCT and stiffness in patients with FS and whether this relationship was modified by patient age. Methods: This study included 540 adults with shoulder pain who had ≥ 10° of limited passive range of motion in forward flexion, compared to the contralateral side. Patients were categorized into 2 groups depending on the degree of forward flexion stiffness: overhead stiffness (OHS) group, patients with ≥ 110° forward flexion (n = 349); and non-OHS group, patients with forward flexion < 110° (n = 191). The presence of concomitant RCT was determined by magnetic resonance imaging and compared between groups before and after stratification by age. Results: The OHS group had increased odds of concomitant RCT, compared to the non-OHS group (odds ratio [OR], 4.99; 95% CI, 3.36–7.42). OHS was also significantly associated with a more severe grade of RCT (no tear, partial-thickness tear, or full-thickness tear) (OR, 4.42; 95% CI, 3.05–6.39). The odds of RCT in the OHS group, compared to the non-OHS group, increased with age (50–59 years: OR, 3.83; 95% CI, 1.96–7.48; 60–69 years: OR, 5.94; 95% CI, 3.14–11.26; and 70–79 years: OR, 7.67; 95% CI, 2.71–21.66). Conclusions Patients with FS and forward flexion range of motion ≥ 110° (i.e., OHS) at initial presentation had approximately 5-fold higher odds of concurrent RCT than patients with non-OHS. Moreover, in patients aged 50 years or above, these odds increased up to almost 8-fold. Therefore, we recommend confirming the rotator cuff integrity with magnetic resonance imaging in patients with FS and OHS.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.