Background/Aims: Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels. Methods: We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015). Results: The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062). Conclusions Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

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.

Systemic corticosteroids play an essential role in the management of asthma. During acute exacerbation, the short-term use of systemic corticosteroids is recommended. For patients with uncontrolled asthma and severe asthma, long-term and low-dose oral corticosteroids (OCS) have frequently been advocated. However, both short-term and long-term use of systemic corticosteroids carry the risk of adverse events (AEs), including various morbidities and even mortality. Despite recent progress in adult severe asthma management and the availability of new treatment options, the current domestic guidelines for asthma do not provide specific recommendations for oral corticosteroid tapering in patients with severe asthma. Therefore, the task force team of the severe asthma working group in the Korean Academy of Allergy, Asthma, and Clinical Immunology has proposed a tapering protocol for systemic corticosteroid use in severe asthma. This includes practical recommendations for monitoring OCS-related AE, particularly for adrenal insufficiency and osteoporosis, which suggests corticosteroid-sparing strategies that include alternative therapies, modifying treatable traits, timely specialist assessment, and shared decision-making with patients. However, further real-world research and collaboration with doctors from primary and academic institutes, patients, and policymakers are necessary to establish an OCS stewardship approach. This should include realistic OCS-tapering strategies for patients with severe asthma using regular OCS, education, and campaigns for patients, the public, and healthcare providers about the burden of severe asthma, as well as improving timely access to specialized severe asthma services for optimal management.

Systemic corticosteroids play an essential role in the management of asthma. During acute exacerbation, the short-term use of systemic corticosteroids is recommended. For patients with uncontrolled asthma and severe asthma, long-term and low-dose oral corticosteroids (OCS) have frequently been advocated. However, both short-term and long-term use of systemic corticosteroids carry the risk of adverse events (AEs), including various morbidities and even mortality. Despite recent progress in adult severe asthma management and the availability of new treatment options, the current domestic guidelines for asthma do not provide specific recommendations for oral corticosteroid tapering in patients with severe asthma. Therefore, the task force team of the severe asthma working group in the Korean Academy of Allergy, Asthma, and Clinical Immunology has proposed a tapering protocol for systemic corticosteroid use in severe asthma. This includes practical recommendations for monitoring OCS-related AE, particularly for adrenal insufficiency and osteoporosis, which suggests corticosteroid-sparing strategies that include alternative therapies, modifying treatable traits, timely specialist assessment, and shared decision-making with patients. However, further real-world research and collaboration with doctors from primary and academic institutes, patients, and policymakers are necessary to establish an OCS stewardship approach. This should include realistic OCS-tapering strategies for patients with severe asthma using regular OCS, education, and campaigns for patients, the public, and healthcare providers about the burden of severe asthma, as well as improving timely access to specialized severe asthma services for optimal management.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to National Comprehensive Cancer Network guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies. Materials and Methods: A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and computed tomography (CT) scans. Results: Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectum). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative carcinoembryonic antigen levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon, 14.9% in rectum). Conclusion Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

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.