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: This study was performed to compare clinical features and emergency department (ED) outcomes between children and adults with non‑typhoidal Salmonella (NTS) gastroenteritis in a single‑center cohort. Methods: We retrospectively reviewed electronic medical records of ED patients with stool multiplex polymerase chain reaction-confirmed NTS at CHA Bundang Medical Center from January 2016 through December 2021. Demographics, presentation, laboratory and imaging findings, microbiology, and treatments were abstracted. Primary outcomes were the high acuity (a Korean Triage and Acuity Scale level 1-2), ED length of stay, and disposition. Results: Of 189 patients, 134 were children and 55 adults. The children had fewer comorbidities (5.2% vs. 56.4%; P < 0.001) and high acuity (children, 0% vs. adults, 14.5%), shorter median ED length of stay (237.0 minutes [interquartile range, 188.0-336.0] vs. 360.0 minutes [335.0-569.0]; difference, 123.0 minutes [95% confidence interval, 85.0-328.0]; P < 0.001), and less frequent hospitalizations to the intensive care unit (children, 0% vs. adults, 14.5%; P < 0.001). Fever (94.8% vs. 63.6%) and hematochezia (37.3% vs. 0%) were more common in the children (Ps < 0.001), while adults had higher frequencies of abdominal pain (87.3% vs. 71.6%; P = 0.020) and enteritis/ileus on radiography (63.3% vs. 45.3%; P = 0.033), and higher median values of segmented white blood cells (79.0% vs. 69.4%; P = 0.010) and C‑reactive protein concentration (7.2 vs. 6.3mg/dL; P < 0.001). Ceftriaxone was more commonly used in the children (children, 72.7% vs. adults, 51.9%; P < 0.001). Conclusion Compared with the adults, the children with NTS gastroenteritis presented with lower clinical acuity, shorter ED stays, and no hospitalizations to the intensive care unit, despite more common fever and hematochezia. These findings may support a conservative ED approach in children with careful, indication‑based antibiotic use and highlight opportunities for antimicrobial stewardship.

Background/Aims: This study investigated the clinical efficacy of low-dose mepolizumab (100 mg) in controlling severe eosinophilic asthma, aiming to induce eosinophilic granulomatosis with polyangiitis (EGPA) remission and reduce systemic steroid usage. Additionally, we constructed a basic frame for our longitudinal EGPA cohort by collecting serial blood samples before, during, and after mepolizumab treatment in EGPA patients. Methods: We conducted a 2-year prospective observational cohort study in patients with uncontrolled severe eosinophilic asthma and refractory EGPA who used systemic steroids (≥ 7.5 mg/day of prednisolone) or other immunosuppressant drugs for at least 6 months. All patients were treated with 100 mg of mepolizumab every 4 weeks for 1 year to control severe eosinophilic asthma and then were followed for an additional 1 year to monitor their disease course. We analyzed total systemic steroid use and EGPA remission/relapse during the study period. Results: Three EGPA patients were included in this study and completed 16 study visits over a 2-year period. After 1 year of treatment with mepolizumab (100 mg monthly), all 3 patients were able to reduce their maintenance dose of systemic steroids, with 2 patients completely discontinuing use. These 2 patients achieved EGPA remission during mepolizumab treatment, and their remission status remained stable for 1 year after they stopped receiving the medication. Conclusions Low-dose mepolizumab treatment demonstrated clinical efficacy in reducing the maintenance dose of systemic steroids required for severe refractory EGPA. While not all patients achieved EGPA remission with low-dose mepolizumab, some did, and their remission persisted even after treatment discontinuation.

Purpose: Cannabidiol (CBD) is a promising treatment option for pediatric drug-resistant epilepsy (DRE). The aim of this study was to assess the tolerability and safety of CBD in a single-center retrospective cohort based on real-world clinical experience. Methods: This study included 71 pediatric patients (median age, 8.9 years; interquartile range [IQR], 6.2 to 14.0) with Lennox–Gastaut syndrome who received purified CBD (Epidiolex, GW Pharmaceuticals) between March 2019 and July 2024. All patients had previously failed treatment with more than five anti-seizure medications (ASMs). Responder rate (≥50% seizure frequency reduction), retention rate, adverse effects (AEs), and predictors of favorable treatment response were analyzed over a median follow-up of 21.3 months (IQR, 2.8 to 38.5). Results: The initial responder rate during the first 3 months was 45.1%, which increased to 70.8% at 18 months and 63.0% at 24 months. The retention rate at 24 months was 52.4% (33/71). Seven patients (9.9%) achieved seizure freedom beyond 24 months of CBD therapy, and five of these patients were able to reduce their concomitant ASM burden. AEs were observed in 39.4% (28/71) of patients, with the most frequent being somnolence (20 cases) and increased seizure frequency (six cases); 92.9% of AEs occurred within the first 3 months of treatment. No serious AEs requiring treatment discontinuation were identified. Conclusion In this real-world study, CBD demonstrated potential as an adjunctive therapy with manageable AEs. These findings highlight that CBD can reduce seizure frequency while maintaining tolerability in pediatric patients with DRE.

Cryopreserved umbilical cord blood (CB) for transplantation is occasionally exposed to room temperature during storage in cord blood banks. We evaluated the effect of room temperature exposure on the quality of cryopreserved CB. Forty frozen CB units stored in liquid nitrogen tanks were exposed to room temperature until they reached a target temperature of –130°C (group I), –60°C (group II), –40°C (group III), or –25°C (group IV) (N = 10 in each group) and then re-stored. After re-thawing, the quality of the frozen CB was assessed based on the recovery rates of cell count, cell viability, and colony-forming unit granulocyte/macrophage (CFU-GM) content. The mean exposure times required to reach the target temperature were 0.83 ± 0.14, 5.92 ± 0.88, 10.28 ± 1.0, and 16.0 ± 1.62 mins for groups I–IV, respectively. CD34+ cell viability was significantly lower in group IV than in the other groups (P = 0.009). The recovery rates of cell counts, cell viability except CD34+cells, and CFU-GM did not significantly differ among the groups. Short-term exposure to room temperature for routine procedures and a temperature rise of up to −40°C during storage do not negatively affect the quality of cryopreserved CB.

Background/Aims: Endoscopic anti-reflux therapy is a therapeutic option for gastroesophageal reflux disease (GERD), providing durable effects. However, clinical data from Korea remain limited. This study evaluates the clinical outcomes of endoscopic radiofrequency Stretta therapy in Korean patients. Methods: A retrospective analysis was conducted on 71 patients with GERD who underwent Stretta therapy at 2 tertiary hospitals in Korea between November 2015 and July 2021. Clinical outcomes, including patient satisfaction, medication cessation or reduction, and complications, were evaluated. Pre- and post-procedural esophageal manometry and 24-hour pH monitoring test results were also analyzed. Results: Patient satisfaction rates at 1, 6, and 12 months post-procedure were 54.7% (35/64), 70.0% (28/40), and 75.0% (21/28), respectively. Medication cessation or reduction was achieved in 31.2% (20/64) at 1 month, 70.0% (28/40) at 6 months, and 67.9% (19/28) at 12 months. Esophageal manometry (n = 21) showed no significant changes in mean lower esophageal sphincter pressure (18.7 mmHg [2.5-52.9] vs 17.4 mmHg [0.0-43.0], P = 0.702) or mean integrated relaxation pressure (8.2 mmHg [0.0-28.0] vs 10.1 mmHg [0.0-31.0], P = 0.840). The 24-hour pH monitoring (n = 18) demonstrated a nonsignificant decrease in acid exposure time (pH < 4) from 2.3% (0.0-8.4) to 1.6% (0.0-7.3) (P = 0.182). Similarly, the DeMeester score decreased non-significantly from 8.4 (0.8-27.7) to 6.6 (0.8-21.8) (P = 0.352). No procedure-related complications occurred. Conclusion Endoscopic radiofrequency Stretta therapy appears to be a safe treatment option for GERD and may provide favorable patient satisfaction and medication reduction.

The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

Background: The existing clinical subtype classification of basal cell carcinoma (BCC) does not adequately reflect tumor invasiveness or its relationship with histologic patterns. Objective: To suggest the upgrading classification of clinical subtype of BCC and evaluate its correlation with histologic subtypes and tumor invasiveness. Methods: This study enrolled 422 patients with 425 biopsy-proven BCC lesions. All of the patients were treated by Mohs micrographic surgery (MMS) at our hospital from January 2018 to October 2021. All BCCs were categorized according to upgrading clinical subtype classification we suggest: Basic subtypes (including nodular [N], papular [P], superficial-elevated [SE]/-flat [SF]/-depressed [SD] and infiltrative [I] subtype) and combined subtype. We conducted a retrospective study through medical record, clinical photographs, pathologic slide and MMS sheets. Results: The most common in basic subtypes was SE (23.1%), followed by N (22.1%) and I (12.0%) subtype. Nodulo-infiltrative (N-I) (8.7%) was the most common in combined subtype.In N, P, SE and SF subtype (non-aggressive group), the rate of tumor with pigmentation (63.1%) was high, non-aggressive pattern (91.4%) in histologic subtype was observed much more. In SD, I and combined subtype (aggressive group), pigmentation (24.0%) was relatively rare, aggressive and mixed pattern (74.4%) in histologic subtype was observed more. More wider surgical margin and more MMS stage number were required in aggressive group than non-aggressive group. Conclusion The upgrading classification of BCC clinical subtype can be not only described briefly and concretely for clinical appearance of BCCs but also highly correlated with histologic subtypes and tumor invasiveness.

Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.