Background: This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management. Methods: Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline. Results: Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%). Conclusion Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

Background: Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells. Methods: CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis. Results: Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells. Conclusion CG-745 may represent a novel therapeutic strategy for NSCLC treatment.

Purpose: The study investigated whether incorporating magnetic resonance imaging (MRI) alongside ultrasonography (US) in the preoperative evaluation is associated with differing survival outcomes between male and female breast cancer patients in a matched analysis. Additionally, clinicopathological prognostic factors were analyzed. Methods: Between January 2005 and December 2020, 93 male and 28,191 female patients who underwent breast surgery were screened. Exact matching analysis was conducted for age, pathologic T and N stages, and molecular subtypes. The clinicopathological characteristics and preoperative imaging methods of the matched cohorts were reviewed. Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier analysis, and Cox proportional hazards regression analysis was used to identify prognostic factors. Results: A total of 328 breast cancer patients (61 men and 267 women) were included in the matched analysis. Male patients had worse DFS (10-year DFS, 70.6% vs. 89.2%; P=0.001) and OS (10-year OS, 64.4% vs. 96.3%; P<0.001) than female patients. The pathologic index cancer size (hazard ratio [HR], 2.013; 95% confidence interval [CI], 1.063 to 3.810; P=0.032) was associated with worse DFS, whereas there were no significant factors associated with OS. Adding MRI to US for preoperative evaluation was not associated with DFS (HR, 1.117; 95% CI, 0.223 to 5.583; P=0.893) or OS (HR, 1.529; 95% CI, 0.300 to 7.781; P=0.609) in male patients. Conclusion Adding breast MRI to US in the preoperative evaluation was not associated with survival outcomes in male breast cancer patients, and the pathologic index cancer size was associated with worse DFS.

Purpose: Although some medications trigger the worsening of myasthenia gravis (MG), their clinical influence on patients with MG has not been significantly evaluated. We aimed to investigate whether the risk of clinical worsening of MG increases after administering cautionary drugs in patients with MG. Materials and Methods: This retrospective case-control study was based on the medical records of patients diagnosed with MG between 2007 and 2020. We analyzed the risk of MG worsening in patients exposed to cautionary drugs during the risk period, defined as 6 months from the first exposure to cautionary drugs. The risk of MG worsening in the exposed patients was compared to that in the non-exposed patients, who were individually matched in a 1:1 ratio with exposed cases for sex, age, thymoma, and autoantibodies. Results: Of the 2002 patients diagnosed with MG, 552 (27.6%) were exposed to cautionary drugs. Neuromuscular blocking agents (320 patients) and beta blockers (66123 person-days) were the most frequently prescribed medications. After exact matching, 220 exposed and 220 non-exposed patients were enrolled. The incidence rate of clinical worsening during the risk period was significantly higher in the exposed patients than in the non-exposed patients (odds ratio=4.09; 95% confidence interval, 1.88–8.90;p<0.001). Clinical worsening was observed in 31 (14.1%) of the exposed patients and in 8 (3.6%) of the non-exposed patients. Conclusion The administration of cautionary drugs increased the risk of clinical worsening in patients with MG. Clinicians should be aware of this risk when cautionary drugs need to be administered.

Purpose: Smoking may have a protective role in developing ulcerative colitis (UC) but have the opposite effect on Crohn’s disease (CD). This study aimed to determine the risk of developing inflammatory bowel disease (IBD) according to smoking status and onset age of smoking. Materials and Methods: We collected data on the smoking experiences of participants aged 20–39 years who underwent biannual examinations provided by the Korean National Health Screening Program from 2009 to 2012. IBD diagnosis was identified using the National Health Insurance Service. The risk of IBD according to smoking status and onset age of smoking was analyzed after adjusting for major clinical variables. Results: During a median 10.59-year follow-up, the risk of UC in ex-smokers was significantly higher than that in non-smokers, and the earlier ex-smokers started smoking, the higher risk of UC [ex-smokers whose onset age of smoking was <20 years, adjusted hazard ratio (aHR) 1.928, 95% confidence interval (CI)=1.649–2.255; 20–24 years, aHR 1.728, 95% CI=1.541–1.939; 25–29 years, aHR 1.676, 95% CI=1.489–1.887; ≥30 years, aHR 1.226, 95% CI=1.010–1.486]. The risk of UC was significantly lower in current smokers whose onset age of smoking was 25–29 years than in non-smokers (aHR 0.825, 95% CI=0.709–0.959). The risk of CD did not differ according to smoking status and onset age of smoking. Conclusion Ex-smokers who started smoking at a young age have a high risk of UC, even after adjusting for the smoking amount.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.