Background: Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates theacetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development oftumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of peripheral neuropathy, a significant non-hematologic side effect. Methods: Animal models of peripheral neuropathy induced by various anti-cancer drugs were established, confirming the potential of HDAC6 inhibitors as a treatment for this condition. Six- to eight-week-old male Sprague Dawley rats were utilized to create these models. Mechanical allodynia and electron microscopy served as indicators of peripheral neuropathy. The HDAC6 inhibitor CKD-011 was administered at doses of 5, 10, 20, and 40 mg/kg. Results: In an animal model of bortezomib-induced peripheral neuropathy, CKD-011, an HDAC6 inhibitor, effectively ameliorated peripheral neuropathy. Similarly, CKD-011 administration demonstrated recovery from peripheral neuropathy in models induced with oxaliplatin, paclitaxel, and cisplatin. Conclusions These findings suggest that HDAC6 inhibitors have the potential to mitigate peripheral neuropathy induced by chemotherapeutic agents.

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: Since the World Health Organization’s pandemic declaration in March 2020, Korea has witnessed shifts in lifestyle behaviors, impacting habits tied to socioeconomic status and contributing to metabolic syndrome (MetS). To investigate this issue, the current study aimed to investigate changes in MetS prevalence, particularly based on income levels before and after the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study used data from the 8th Korea National Health and Nutrition Examination Survey (2019–2020). A total of 6,840 individuals aged 30–65 years were included in this study. Household income was divided into high (≥75th percentile), middle (25–75th percentile), and low (≤25th percentile). A multivariable logistic regression analysis was performed to explore the interaction between this association before and after the COVID-19 pandemic. Results: A statistically significant difference was found in the prevalence of MetS before and after the COVID-19 pandemic (26.7% to 30.2%, P=0.001). These changes differed based on income levels. The increase in the prevalence of MetS was statistically significant in the low- and high-income groups but not in the middle-income group (low: 8.0%p increase [P=0.039], middle: 1.0%p increase [P=0.522], high: 6.4%p increase [P<0.001]). The interaction between household income and the COVID-19 pandemic on MetS was statistically significant (P for interaction=0.032). Conclusion This study revealed that P for interaction between household income, MetS, and the period before and after the COVID-19 pandemic was significant. Changes in physical activity and eating habits during the COVID-19 pandemic may have contributed to these differences.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Background/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with <4 years, 4–9 years, and ≥10 years of experiencein colonoscopy practices accounted for 25.6%, 34.1%, and 40.2% of endoscopists, respectively. The most preferred resection methods for non-pedunculated lesions were cold forceps polypectomy for ≤3 mm lesions (81.7%), cold snare polypectomy for 4–5 mm (61.0%) and 6–9 mm (43.5%) lesions, hot endoscopic mucosal resection (EMR) for 10–19 mm lesions (72.0%), precut EMR for 20–25 mm lesions (22.0%), and endoscopic submucosal dissection (ESD) for ≥26 mm lesions (29.3%). Hot EMR was favored for pedunculated lesions with a head size <20 mm and stalk size <10 mm (75.6%) and for those with a head size ≥20 mm or stalk size ≥10 mm (58.5%). For suspected superficial and deep submucosal lesions measuring 10–19 mm and ≥20 mm, ESD (26.0% and 38.6%) and surgery (36.6% and 46.3%) were preferred, respectively. The adherence rate to the guidelines ranged from 11.2% to 96.9%, depending on the size, shape, and histology of the lesions. Conclusions Adherence to the guidelines for endoscopic resection techniques varied depend-ing on the characteristics of colorectal polyps. Thus, an individualized approach is required to increase adherence to the guidelines.

Objectives: Assessing medical disputes requires both medical and legal expertise, presenting challenges for patients seeking clarity regarding potential malpractice claims. This study aimed to develop and evaluate a chatbot based on a chain-of-thought pipeline using a large language model (LLM) for providing medical dispute counseling and compare its performance with responses from human experts. Methods: Retrospective counseling cases (n = 279) were collected from the Korea Medical Dispute Mediation and Arbitration Agency’s website, from which 50 cases were randomly selected as a validation dataset. The Claude 3.5 Sonnet model processed each counseling request through a five-step chain-of-thought pipeline. Thirty-eight experts evaluated the chatbot’s responses against the original human expert responses, rating them across four dimensions on a 5-point Likert scale. Statistical analyses were conducted using Wilcoxon signed-rank tests. Results: The chatbot significantly outperformed human experts in quality of information (p < 0.001), understanding and reasoning (p < 0.001), and overall satisfaction (p < 0.001). It also demonstrated a stronger tendency to produce opinion-driven content (p < 0.001). Despite generally high scores, evaluators noted specific instances where the chatbot encountered difficulties. Conclusions A chain-of-thought–based LLM chatbot shows promise for enhancing the quality of medical dispute counseling, outperforming human experts across key evaluation metrics. Future research should address inaccuracies resulting from legal and contextual variability, investigate patient acceptance, and further refine the chatbot’s performance in domain-specific applications.

Objectives: This study was performed to evaluate the utilization patterns of acid suppressants following the withdrawal of ranitidine in Korea. Methods: Health Insurance Review & Assessment Service (HIRA) data from January 2016 to May 2023 were utilized to assess the usage of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) for acid-related diseases. Drug utilization was calculated for each agent based on the defined daily dose (DDD). To evaluate changes in utilization following the ranitidine recall, an interrupted time series analysis was conducted using segmented linear regression and an autoregressive integrated moving average model. Results: Before the withdrawal of ranitidine, the DDD per 100 000 inhabitants per day was increasing by 6.9 (95% confidence interval [CI], 4.7 to 9.0) for H2RAs and by 19.3 (95% CI, 16.9 to 21.8) for PPIs each month. After the recall, H2RA utilization immediately declined by -1041.7 (95% CI, -1115.8 to -967.7), followed by a monthly increase of 6.6 (95% CI, 3.7 to 9.6) above the previous trend. PPI utilization temporarily surged by 235.2 (95% CI, 149.1 to 321.3), then displayed a monthly increase of 4.1 (95% CI, 0.7 to 7.6) on top of the pre-recall trend. Among PPIs, esomeprazole and rabeprazole demonstrated notable increases, representing the most commonly used acid suppressants in 2023. Conclusions PPI usage rose prominently following the withdrawal of ranitidine from the market. Considering the potential adverse effects of PPIs, further research is necessary to evaluate the public health implications of shifts in the utilization of acid suppressants.

Background: Since the World Health Organization’s pandemic declaration in March 2020, Korea has witnessed shifts in lifestyle behaviors, impacting habits tied to socioeconomic status and contributing to metabolic syndrome (MetS). To investigate this issue, the current study aimed to investigate changes in MetS prevalence, particularly based on income levels before and after the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study used data from the 8th Korea National Health and Nutrition Examination Survey (2019–2020). A total of 6,840 individuals aged 30–65 years were included in this study. Household income was divided into high (≥75th percentile), middle (25–75th percentile), and low (≤25th percentile). A multivariable logistic regression analysis was performed to explore the interaction between this association before and after the COVID-19 pandemic. Results: A statistically significant difference was found in the prevalence of MetS before and after the COVID-19 pandemic (26.7% to 30.2%, P=0.001). These changes differed based on income levels. The increase in the prevalence of MetS was statistically significant in the low- and high-income groups but not in the middle-income group (low: 8.0%p increase [P=0.039], middle: 1.0%p increase [P=0.522], high: 6.4%p increase [P<0.001]). The interaction between household income and the COVID-19 pandemic on MetS was statistically significant (P for interaction=0.032). Conclusion This study revealed that P for interaction between household income, MetS, and the period before and after the COVID-19 pandemic was significant. Changes in physical activity and eating habits during the COVID-19 pandemic may have contributed to these differences.