This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.

Metaverse-based mental health interventions have recently emerged as an extension of telepsychiatry, digital therapeutics (DTx), and virtual reality (VR)–based treatments for children and adolescents. The coronavirus disease 2019 pandemic accelerated the adoption of remote psychological assessment and intervention, raising critical questions regarding their clinical validity, developmental appropriateness, and long-term applicability in youth populations. Accumulating evidence has demonstrated that remote assessments and internet-based interventions can achieve clinical outcomes comparable to face-to-face approaches in selected domains, particularly anxiety, depression, and social communication difficulties. In parallel, immersive technologies such as VR and metaverse-based platforms have been applied to exposure-based interventions, social skills training, and emotion regulation in controlled and repeatable environments. This narrative review examined 48 empirical and review studies on telepsychiatry, internet-based cognitive behavioral therapy, DTx, VR, and metaverse-based interventions for children and adolescents. Neurobiological mechanisms relevant to fear extinction, executive function, emotion regulation, and social cognition were critically reviewed. In addition, real-world implementation experiences from a hospital-based Wee Center in Korea were integrated to evaluate feasibility within school-linked mental health services. The findings suggested that metaverse-based counseling should not be conceptualized as a stand-alone replacement for face-to-face treatment, but rather as a complementary, hybrid platform linking remote screening, structured digital intervention, and in-person clinical care. While current evidence supported feasibility and conditional clinical utility, further longitudinal, controlled, and cost-effectiveness studies were required to establish its role in pediatric mental health.

Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

Background: Nonalcoholic fatty liver disease, a progressive condition caused by the accumulation of fat in the liver, begins with simple steatosis and can potentially progress to metabolic dysfunction-associated steatohepatitis (MASH) in the presence of inflammation and fibrosis, ultimately leading to cirrhosis or hepatocellular carcinoma. Increasing evidence indicates that sodiumglucose cotransporter 2 (SGLT2) inhibitors effectively alleviate MASH in mouse models. However, there is a lack of research on the effects of enavogliflozin on liver disease. In the present study, we investigated the effects of SGLT2 inhibitors on MASH induced by a high-fat, high-cholesterol (HFHC) diet in mice. Methods: Male C57BL/6 mice were fed a normal chow diet, HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. LX-2 and HepG2 cells were treated with enavogliflozin in the presence of various pathological stimuli. Results: The HFHC diet induced excessive hepatic lipid accumulation, inflammation, and severe fibrosis. Administration of enavogliflozin not only ameliorated hepatic steatosis and fibrotic conditions but also suppressed the production of inflammatory cytokines. Positive outcomes were also observed in in vitro experiments, where enavogliflozin demonstrated the ability to impede the activation of hepatic stellate cells and alleviate lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the transforming growth factor β1/Smad signaling pathway. Conclusion Our results suggest that enavogliflozin is effective in a mouse model of MASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis.

Background: Multiple perinatal factors influence hemodynamically significant patent ductus arteriosus (HS PDA) in preterm infants.Purpose: This study aimed to identify the risk factors associated with HS PDA in very low birth weight infants (VLBWIs) and determine the predictors of surgical ligation. Methods: This retrospective study included VLBWIs born at 23–32 weeks’ gestation whose HS PDA properties could be identified using echocardiography. The infants were stratified into 2 groups based on gestational age (23–27 and 28–32 weeks). Results: Among the 496 included VLBWIs, 171 had no PDA, 90 had non-HS PDA, and 235 had HS PDA. In infants born at 23–27 weeks’ gestation, risk factors for HS PDA included low birth weight, the absence of histological chorioamnionitis, and premature rupture of membranes. For VLBWIs born at 28–32 weeks’ gestation, HS PDA was associated with lower birth weight, frequent surfactant treatment, and maternal hypertension. Within the HS PDA group, infants with a lower birth weight or who received incomplete antenatal steroid administration had an increased likelihood of requiring surgical ligation, whereas those with a small-for-gestational-age status had a decreased need for surgical ligation. Conclusion Recognizing these risk factors can aid the development of targeted treatment strategies for HS PDA in VLBWIs, enabling early ligation and potentially reducing the need for surgical management.

Purpose: This study aimed to develop and implement an antimicrobial stewardship education program for physician assistant nurses and to evaluate its effects on their knowledge and clinical performance. Methods: A quasi-experimental, single-group pre-post design was conducted with 50 physician assistant nurses at a university hospital in Seoul, Republic of Korea. The antimicrobial stewardship education program, developed using the ADDIE model, consisted of 12 sessions including lectures and case-based learning (CBL)-based discussions.Knowledge was measured before and immediately after the intervention, while performance was assessed pre-intervention and four weeks post-program. Data were analyzed using paired t-tests, Wilcoxon signed-rank tests, and analysis of covariance (ANCOVA). Results: Knowledge scores significantly improved from 44.65±7.45 to 58.50±10.11 (p<.001), and all subdomains showed significant increases (p<.001). Performance scores increased from 3.68±0.77 to 4.28±0.68 (p<.001). Knowledge gain did not differ significantly between the medical and surgical departments (p=.710). Likewise, after adjusting for pre-test scores, no significant difference in performance improvement was observed between the two departments (ANCOVA, p=.170). These results indicate that the program was effective across both departments regardless of their characteristics. Conclusion The antimicrobial stewardship education program improved both knowledge and performance among physician assistant nurses. This program may contribute to the standardization of antimicrobial stewardship education and to appropriate antimicrobial use and the reduction of antimicrobial resistance.

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.

Purpose: The purpose of this study was to develop an approach to alleviate the discomfort caused by sandbag compression after a bone marrow examination. This research examined the effects of applying a pressure hemostasis band on bleeding, pain, and discomfort at the bone marrow examination site. Methods: This study was conducted with a nonequivalent control group non-synchronized design. For 74 patients under evaluation who underwent bone marrow examination, sandbag compression was applied to the examination site in the control group (n=37), and a pressure hemostasis band was applied to the intervention group (n=37). In both groups, absolute bed rest was performed for two hours, and bleeding, pain, and discomfort at the examination site were measured. Results: After two hours of the bone marrow examination, there was no difference in bleeding on the gauze between the two groups (F=0.59, p=.444). Bleeding occurred in three patients in the intervention group and six in the control group (χ 2 =1.14, p=.479), with no cases of hematoma detected in either group. One hour post-examination, the control group experienced significantly higher pain (F=5.45, p=.022) and discomfort (F=5.68, p=.020) than the intervention group. However, pain and discomfort levels were similar between groups after two hours. Conclusion Compared to the sandbag compression group, the band application group showed no difference in bleeding and experienced less pain and discomfort at the examination site. This confirms that the pressure hemostasis band is a suitable alternative to sandbag compression in post-examination care.