Background: The Act on Decisions on Life-Sustaining Treatment (LST) has been implemented in Korea since 2018, yet data on its application in neurocritical care units remain scarce. This study aimed to evaluate the clinical characteristics and outcomes of LST withdrawal or withholding in the neurocritical care unit. Methods: This study was a retrospective analysis conducted at a tertiary university hospital in Busan, South Korea. Among patients admitted to the neurocritical care unit between February 2018 and August 2023, those with documented decisions for LST withdrawal or withholding were enrolled. Demographic and clinical characteristics, underlying and combined conditions, reasons for LST decisions, measures taken, and time from LST withdrawal to death were extracted from medical records. Results: A total of 69 patients were included, with a median age of 67 years, and 38 (55%) were male. Cerebrovascular disease (62%) and traumatic brain injury (22%) were the most common underlying diagnoses. The primary reason for LST decisions was irreversible neurological damage (71%), followed by systemic complications (19%). Mechanical ventilation cessation (91%) and extubation (86%) were most frequently used measures for LST withdrawal. The median time from LST withdrawal to death was 22 minutes. Conclusions Our study demonstrates that LST decisions in the neurocritical care unit predominantly occur among patients with cerebrovascular disease or traumatic brain injury, mostly triggered by neurological deterioration. Most patients died shortly after withdrawal. These findings provide important insight into current LST withdrawal practices in neurocritical care and may assist clinical and ethical decision making in similar settings.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Background: Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases. Methods: Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis. Results: All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases. Conclusions Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine known for its hemodynamic stability over propofol. However, its hemodynamic effects compared to those of etomidate are not well established. This study aimed to determine whether the use of remimazolam is non-inferior to etomidate with regard to the occurrence of post-induction hypotension in patients undergoing coronary artery bypass grafting. Methods: Patients were randomly assigned to either the remimazolam group (6 mg/kg/h) or the etomidate group (0.3 mg/kg) for induction of anesthesia. Anesthetic depth was adjusted based on the bispectral index. Primary outcome was the incidence of post-induction hypotension, defined as a mean arterial pressure less than 65 mmHg within 15 min after endotracheal intubation, with a non-inferiority margin of 12%. Results: A total of 144 patients were finally analyzed. Incidence of post-induction hypotension was 36/71 (50.7%) in the remimazolam group and 25/73 (34.2%) in the etomidate group, with a rate difference of 16.5% (95% CI [3.0–32.6]) between the two groups that was beyond the prespecified non-inferiority margin of 12.0%. The number of patients who needed vasopressors was similar in the two groups. Conclusions In this non-inferiority trial, remimazolam failed to show non-inferiority to etomidate in terms of post-induction hypotension when used as an induction drug for general anesthesia in patients undergoing coronary artery bypass grafting. However, different doses or infusion techniques of remimazolam should be compared with etomidate in various patient groups to fully assess its hemodynamic non-inferiority during induction of anesthesia.

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.

Background: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. Conclusion In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Background/Aims: The incidence of steatotic liver disease (SLD) is increasing across all age groups as the incidence of obesity increases worldwide. The existing noninvasive prediction models for SLD require laboratory tests or imaging and perform poorly in the early diagnosis of infrequently screened populations such as young adults and individuals with healthcare disparities. We developed a machine learning-based point-of-care prediction model for SLD that is readily available to the broader population with the aim of facilitating early detection and timely intervention and ultimately reducing the burden of SLD. Methods: We retrospectively analyzed the clinical data of 28,506 adults who had routine health check-ups in South Korea from January to December 2022. A total of 229,162 individuals were included in the external validation study. Data were analyzed and predictions were made using a logistic regression model with machine learning algorithms. Results: A total of 20,094 individuals were categorized into SLD and non-SLD groups on the basis of the presence of fatty liver disease. We developed three prediction models: SLD model 1, which included age and body mass index (BMI); SLD model 2, which included BMI and body fat per muscle mass; and SLD model 3, which included BMI and visceral fat per muscle mass. In the derivation cohort, the area under the receiver operating characteristic curve (AUROC) was 0.817 for model 1, 0.821 for model 2, and 0.820 for model 3. In the internal validation cohort, 86.9% of individuals were correctly classified by the SLD models. The external validation study revealed an AUROC above 0.84 for all the models. Conclusions As our three novel SLD prediction models are cost-effective, noninvasive, and accessible, they could serve as validated clinical tools for mass screening of SLD.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.