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: 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.

Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) can range from mild cutaneous symptoms to life-threatening anaphylaxis. In patients with a history of ICM hypersensitivity, avoidance of the culprit agent is generally recommended. This case report describes a successful desensitization in a 56-year-old man with recurrent HSRs to multiple agents including ioversol, iohexol, iobitridol, and iopamidol. Intradermal testing was performed to identify potentially safe alternatives; however, all tested agents, including iohexol, ioversol, iobitridol, iopamidol, iodixanol, iomeprol, and iopromide, yielded positive results. Given the clinical necessity of transcatheter arterial chemoembolization, a 13-step rapid desensitization protocol with iodixanol was implemented. The procedure was completed without any breakthrough reactions. This case highlights desensitization as a feasible and effective strategy for patients with hypersensitivity to multiple ICM agents.

Background: Despite widespread vaccination efforts against severe acute respiratory syndrome coronavirus 2, variants with increased transmissibility or immune evasion continue to emerge, posing a considerable challenge. Understanding the immunological factors associated with coronavirus disease (COVID-19) progression is essential for improving patient management and treatment strategies. We explored the dynamic changes in the peripheral white blood cell (WBC) profile, including T lymphocyte subsets, to assess their potential as predictors of disease severity and progression. Methods: Two hundred fifty-eight patients hospitalized for confirmed COVID-19 were classified into four sub-cohorts based on changes in disease severity over 7 days. WBC parameters, including absolute neutrophil, total lymphocyte, and T cell subset counts, and the neutrophil-to-lymphocyte ratio (NLR) were assessed at admission and after 7 days. Results: Patients with persistent mild-to-moderate illness exhibited a marked increase in the lymphocyte count and a decrease in the NLR over time. In contrast, patients with sustained severe-to-critical illness showed an increasing WBC count without a corresponding increase in the lymphocyte count, in addition to a marked elevation in the NLR. Patients whose condition improved from severe-to-critical to mild-to-moderate illness showed increased cluster of differentiation (CD)3+ and CD4+ T cell counts and an elevated CD4/CD8 ratio, whereas the NLR did not significantly change. Conclusions The early-phase dynamics of T cell subsets may serve as a useful biomarker of disease severity and recovery in patients with COVID-19. Monitoring these immunological changes may help support clinical decision-making and inform the timing of therapeutic interventions.

The gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Between the 1990s and early 2000s, GIST was identified as a tumor characterized by KIT or PDGFRA mutations, resulting in imatinib being established as an effective targeted therapy. However, with advances in molecular diagnostics, approximately 10%–15% of GISTs have been reported to harbor alternative mutations, such as those in the succinate dehydrogenase subunit genes and BRAF, leading to the development of additional targeted therapies. GISTs exhibit a wide spectrum of clinical behaviors, ranging from indolent to highly aggressive, prompting the development of diverse risk classification systems. However, multiple systems remain in use, leading to inconsistent pathologic reports. Moreover, the mitotic counting method—a key factor in risk stratification—has become a major source of confusion among pathologists owing to the adoption of digital pathology and discrepancies between updated international guidelines and outdated reimbursement requirements. These inconsistencies have hindered pathologic reporting and communication between pathologists and clinicians. This review comprehensively overviews the historical background, molecular subtypes, and risk classification systems of GIST, focusing on evolving issues in mitotic rate evaluation and the application of risk classification systems in clinical practice.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Purpose: This study aimed to investigate the impact of physical activity on dementia risk among cancer survivors in South Korea. Materials and Methods: This retrospective, population-based cohort study included 344,152 cancer survivors identified from the National Health Insurance Service database in South Korea. The mean follow-up time was 5.81 years. Different levels of physical activity post-cancer diagnosis, ranging from inactive to highly active, were assessed. The primary outcome was the incidence of overall dementia, Alzheimer’s disease, and vascular dementia. Secondary outcomes included dementia risk stratified by cancer type and treatment (chemotherapy and radiation). Results: Of the total participants, 24,363 (7.08%) developed dementia. The risk of overall dementia decreased sequentially across the exercise groups compared to the inactive group: insufficiently active (adjusted hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.86 to 0.92), active (adjusted HR, 0.85; 95% CI, 0.83 to 0.88), and highly active (adjusted HR, 0.79; 95% CI, 0.76 to 0.82). This inverse relationship between exercise and dementia risk was statistically significant across various cancer types and was consistent regardless of age, comorbidities, and whether or not excluding the first 1, 2 years. Conclusion Among cancer survivors in South Korea, increased physical activity post-diagnosis was associated with a significantly lower risk of dementia. These findings underscore the importance of promoting physical activity in cancer survivors for cognitive health.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.