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: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

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.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

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.

South Korea’s current vaccination policies leave a surveillance gap for non-National Immunization Program (NIP) vaccines. In this study, we proposed a sentinel surveillance approach for monitoring the safety of non-NIP vaccines. Vaccination data were collected retrospectively among patients hospitalized with pre-defined adverse events of special interest (AESI) by reviewing electronic medical records in five university hospitals. This approach incorporates expert assessment to determine the causal relationship. We confirmed that 16 patients had received non-NIP vaccines among 860 patients diagnosed with AESI.We concluded one case of preeclampsia was possibly related to tetanus-diphtheria-pertussis vaccination. We propose a multi-hospital-based, retrospective assessment system for predefined AESIs as an alternative to active vaccine safety monitoring method. These efforts are expected to enhance both the accuracy and timeliness of safety monitoring in South Korea.

Background: Tinnitus is a multifactorial condition with no universally accepted assessment guidelines. The Korean Tinnitus Study Group previously established consensus statements on the definition, classification, and diagnostic tests for tinnitus. As a continuation of this effort, this study aims to establish expert consensus on tinnitus assessment and treatment outcome evaluation, specifically tailored to the Korean clinical context. Methods: A modified Delphi method involving 26 otology experts from across Korea was used. A two-round Delphi survey was conducted to evaluate statements related to tinnitus assessment before and after treatment. Statements were rated on a scale of 1 to 9 for the level of agreement. Consensus was defined as ≥ 70% agreement (score of 7–9) and ≤ 15% disagreement (score of 1–3). Statistical measures such as content validity ratio and Kendall’s coefficient of concordance (W) were calculated to assess agreement levels. Results: Of the 46 assessment-related statements, 17 (37%) reached consensus, though overall pre-treatment assessments showed weak agreement (Kendall’s W = 0.319). Key areas of agreement included the use of the visual analogue scale, numeric rating scale, and validated questionnaires for pre-treatment evaluation. Five statements, such as the use of computed tomography, magnetic resonance imaging, and angiography for diagnosing pulsatile tinnitus, achieved over 90% agreement. For treatment outcome measurements, 8 of 12 statements (67%) reached a consensus, with moderate agreement (Kendall’s W = 0.513). Validated questionnaires and psychoacoustic tests were recommended for evaluating treatment effects within 12 weeks. While standardized imaging for pulsatile tinnitus and additional clinical tests were strongly recommended, full consensus was not achieved across all imaging modalities. Conclusion This study provides actionable recommendations for tinnitus assessment and treatment evaluation, emphasizing the use of standardized tools and individualized approaches based on patient needs. These findings offer a practical framework to enhance consistency and effectiveness in tinnitus management within Korean clinical settings.

Background: Korea National Health and Nutrition Examination Survey (KNHANES) triglyceride testing changed from the glycerol blanking method (2005–2021) to the glycerol nonblanking method (2022). We converted triglyceride data from 2005–2021 to that obtained since 2022 with different analytical methods. Methods: To develop a conversion equation, 98 fresh serum specimen pairs were compared using Passing–Bablok regression analysis. Implications of the conversion equation on epidemiological data were evaluated using KNHANES data from 2019–2021. Bias estimations determined using the Lipid Standardization Program (LSP) of the United States Centers for Disease Control and Prevention (CDC) enhanced the accuracy and comparability of the triglyceride results. Results: Triglyceride concentrations measured via the glycerol non-blanking method were 10.7 mg/dL (0.12 mmol/L, 10.0%) higher than those from the glycerol blanking method, with a 9.9 mg/dL (0.11 mmol/L, 5.0%) difference at a concentration of 200 mg/dL (2.26 mmol/L, N = 98). The conversion equation y (glycerol non-blanking, 2022) = 11.94+0.99x (glycerol blanking, 2005–2021) changed the mean triglyceride concentrations of the KNHANES 2019–2021 data (N = 16,015) from 123.7 mg/dL (1.40 mmol/L, 95% confidence interval [CI]: 122.2–125.1 mg/dL [1.38–1.41 mmol/L]) to 134.3 mg/dL (1.52 mmol/L, 95% CI: 132.9–135.8 mg/dL [1.50–1.53 mmol/L]). Since 2022, bias monitoring using the CDC’s LSP has remained within a 5.0% limit. Conclusions KNHANES triglyceride values in 2022 (non-blanking) were substantially higher than those from 2005–2021 (blanking). Conversion equations helped effectively adjust 2005–2021 data. Researchers should consider adjusting the KNHANES triglyceride data based on their study characteristics.