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.

Sleep–wake regulation is controlled by circadian and homeostatic processes, with adenosine acting as a key molecular mediator of homeostatic sleep pressure. Extracellular adenosine accumulates during wakefulness as a result of neuronal energy metabolism, particularly in the basal forebrain, and declines during recovery sleep, thereby reflecting the physiological need for sleep.The sleep-promoting effects of adenosine are mediated primarily by two G protein–coupled receptor subtypes, the adenosine A1 receptor and the adenosine A2A receptor. The adenosine A1 receptor, coupled to inhibitory Gi/o proteins and widely expressed in the cortex, hippocampus, thalamus, and basal forebrain, suppresses wake-promoting neuronal activity and facilitates slow-wave activity during non-rapid eye movement sleep. In contrast, the adenosine A2A receptor, coupled to stimulatory Golf proteins and enriched in the striatum and nucleus accumbens, promotes sleep by activating neurons in the preoptic hypothalamus and engaging the indirect basal ganglia pathway. Despite these well-established roles, the contributions of dysregulation of the adenosine A1 receptor and the adenosine A2A receptor to specific sleep disorders remain incompletely understood. This review examines how signaling of the adenosine A1 receptor and the adenosine A2A receptor is altered in insomnia, obstructive sleep apnea, narcolepsy, and restless legs syndrome, and evaluates the therapeutic potential of receptor-selective strategies for adenosine receptor–targeted treatment.

Background: and Purpose: Tailored physical exercise interventions have the potential to promote cognitive health in older adults and offer significant advantages for those more vulnerable to decline. The specific relationship between physical fitness and cognition among the elderly has not been clearly established. The purpose of this investigation was to assess the relationship between physical fitness and cognitive function in older Korean adults. Methods: Eighty-four community-dwelling older adults (mean age: 70.7±5.3 years; 81.0% female) completed a standardized physical fitness battery assessing handgrip strength, sit-and-reach, 30-second sit-to-stand, 2-minute stationary march, 3-m sit-walk-and-return, figure-8-walk, and T-wall response time. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Descriptive statistics, partial correlation analyses, and stepwise multiple linear regression were conducted. Results: Slower T-wall response time was significantly correlated with lower RBANS total index, immediate memory, and delayed memory scores. In regression models, slower T-wall response time was independently associated with lower RBANS total index (β=−0.234, p=0.026) and delayed memory scores (β=−0.295, p=0.029). The regression model for immediate memory was not statistically significant overall; therefore, no predictive conclusion was drawn for this domain. Higher education showed a significant positive association with cognitive performance. Conclusions Coordination, as measured by T-wall response time, emerged as the only physical fitness component consistently associated with cognitive performance in older adults. Coordination-related fitness may be an important correlate of cognitive function in older adults and a promising target for future exercise interventions.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Objectives: Lonely death is defined as “a person living in a state of social isolation, disconnected from family, relatives, and others, who dies from suicide, illness, or other causes”. This study investigated the characteristics of individuals who die alone in Korea. Methods: We constructed a database of lonely death cases by linking data from the Korea Crime Scene Investigation Unit of the Korea National Police Agency with National Health Insurance Service (NHIS) records. A descriptive analysis was performed to evaluate the demographics, underlying diseases, and healthcare utilization patterns among lonely death cases. Results: Among the 3122 individuals identified as lonely death cases, 2621 (84.0%) were male and 501 (16.0%) were female. The most common age group was 50-59 years (n=930, 29.8%). The NHIS covered 2161 individuals (69.2%), whereas 961 individuals (30.8%) were enrolled in Medical Aid (MA). The highest number of lonely deaths occurred in Seoul areas, with 1468 cases (47.0%). Mood disorders were diagnosed in 1020 individuals (32.7%), and various alcohol-related diseases, including alcoholic liver disease, were also observed. Outpatient visits increased leading up to death but declined in the final 3 months, while hospitalizations decreased and emergency room visits slightly increased. Conclusions Most lonely death cases involved male in their 50s, with a disproportionately high number of MA beneficiaries compared to the general population. Many of these individuals also experienced mental health issues or alcohol-related disorders. Preventing social isolation and strengthening social safety nets are critical to reducing the occurrence of lonely deaths.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is extremely rare in pediatric patients. Here, we report the case of an 8-year-old boy with iron-deficiency anemia and a solitary splenic mass detected using US, CT, and MRI. The patient underwent partial splenectomy, and the final diagnosis was SANT. Herein, we discuss the radiological features of splenic SANT through a review of reported cases and the differential diagnosis of other primary splenic tumors.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Purpose: This study aimed to develop a Korean version of the frailty model that reflects a holistic perspective. There were three phases of the study: a literature review, a two-round Delphi study, and a public hearing. Methods: The model was developed based on the middle-range theory generation approach proposed by Roy. A literature search was conducted, and a review of 36 studies on frailty involving Koreans led to the development of an initial frailty model. A two-round Delphi study was then conducted with nine experts to evaluate the appropriateness of the model. The revised model was presented at a public hearing to achieve consensus. Based on feedback indicating the need for improved visualization, a finalized diagrammatic model was developed. Results: The final frailty model comprised four domains, seven subdomains, and 30 items. It included specific items reflecting the distinctive characteristics of Korean culture, such as relationships with adult children (filial piety), nutritional status (consumption of red meat), and type of residential building. Conclusion The final frailty model provides a comprehensive perspective on the factors contributing to frailty, their interactions, and the potential interventions that healthcare providers can implement to prevent frailty.