Background: Erythema multiforme (EM) is typically a self-limited, acute hypersensitivity reaction. However, a subset of patients experiences chronic, recurrent episodes, for which clinical features and treatment strategies differ depending on the underlying etiology, especially in herpes simplex virus (HSV)-associated cases. Objective: To investigate the clinical and phenotypic features of chronic recurrent EM and assess treatment responses, with a focus on differences based on HSV association. Methods: This retrospective study included pathology-confirmed cases of suspected EM from 2010 to 2023. Forty patients with chronic EM (≥3 recurrences or persistent disease for ≥12 months) were included. Clinical, histopathologic, and serologic data were analysed.Patients were stratified into herpes simplex virus-associated erythema multiforme (HAEM) and non-HAEM groups. Clustering analysis was performed to identify clinical phenotypes.Treatment responses to antivirals and immunomodulators were evaluated. Results: Of the 40 patients, 24 (60%) were classified as HAEM. HAEM patients showed more mucosal involvement, smaller targetoid lesions, and acral predominance, while nonHAEM patients had larger, coalescing lesions with more trunk involvement. Cluster analysis supported HSV as the major discriminating factor. Antiviral agents were effective in 87.5% of HAEM cases but ineffective in 76.9% of non-HAEM patients. Immunosuppressants such as cyclosporine and mycophenolate mofetil showed variable responses. Baricitinib induced complete remission in all 3 refractory cases. Conclusion HSV association defines a distinct clinical subtype of chronic recurrent EM, with differences in lesion morphology, distribution, and treatment response. Recognizing these patterns may guide targeted therapeutic strategies, including the potential use of Janus kinase inhibitors in refractory cases.

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.

Objective: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) constitute the standard systemic treatment for estrogen receptor-positive, human epidermal growth factor 2-negative (ER+/HER2-) metastatic breast cancer (MBC). However, treatment responses remain heterogeneous, highlighting the need for reliable prognostic markers. This study aimed to evaluate the prognostic significance of 18F-fluorodeoxyglucose (FDG) PET/CT findings in this setting. Materials and Methods: This retrospective single-center cohort study included patients with ER+/HER2- MBC who underwent18F-FDG PET/CT before initiating CDK4/6 inhibitors plus ET between 2018 and 2023. Maximum standardized uptake value(SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Progression-free survival (PFS) and overall survival (OS) were evaluated as the primary and secondary outcomes, respectively, using multivariable Cox models. PET parameters (SUVmax, MTV, and TLG) were analyzed as both continuous and dichotomized variables based on median values, adjusting for relevant clinical covariates. Results: Among the 374 patients, 82 (21.9%) presented with de novo metastatic disease, and 357 (95.5%) received CDK4/6 inhibitors as first-line therapy. In multivariable Cox analysis, all continuous PET parameters were independently associated with PFS (adjusted hazard ratio for SUVmax 1.05 [95% confidence interval 1.02–1.08]; log-transformed MTV 1.16 [1.08–1.25]; and log-transformed TLG 1.14 [1.07–1.23]) and OS (SUVmax 1.08 [1.04–1.11]; log-transformed MTV 1.24 [1.12–1.38]; and log-transformed TLG 1.22 [1.11–1.34]) with all P < 0.001. Results based on dichotomized PET parameters were similar to those obtained with continuous values: PFS (adjusted hazard ratio for SUVmax ≥ 7.6, 1.41 [1.08–1.85]; MTV ≥ 21.2 cm 3 , 1.41 [1.08–1.86]; and TLG ≥ 78.9, 1.51 [1.14–1.99]) with P ≤ 0.013 and OS (1.43 [1.01–2.04]; 1.84 [1.28– 2.66]; and 1.73 [1.20–2.50], respectively) with P ≤ 0.046. Conclusion Pretreatment 18F-FDG PET/CT parameters are independent prognostic markers in patients with ER+/HER2- MBC receiving CDK4/6 inhibitors with ET, supporting their potential utility in risk stratification.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background/Aims: Cardiovascular disease is the leading cause of death worldwide. This study aimed to investigate the recent nationwide trends in major dietary risk factors for dyslipidemia and atherosclerosis. Methods: We estimated age-standardized mean intakes of fresh fruits, fresh vegetables, whole grains, dietary fiber, and sugar-sweetened beverages (SSBs); and mean percentage of energy intake from protein, total fat, saturated fat, and polyunsaturated fat using nationally representative samples from the Korean National Health Examination and Nutrition Survey 2013–2022. To assess overall diet quality, we calculated mean Korean Healthy Eating Index (KHEI) (range 0–100, higher scores indicating greater diet quality). Results: In 2013–2022, there were overall decreasing trends in age-standardized mean KHEI score and intakes of fresh fruits and vegetables, whole grains, and dietary fiber; and overall increasing trends in mean intakes of SSBs, protein, and dietary fat among both male and female. The KHEI score increased in older adults aged ≥ 60 years, whereas it decreased among younger adults. Throughout the study period, younger adults tended to have lower intakes of fresh fruits, fresh vegetables, and whole grains; higher intakes of SSBs, protein, and dietary fat; and lower KHEI score. The mean KHEI score was lower in male (vs. female) and lower (vs. higher) income groups. Conclusions Our data suggest that, from 2013 to 2022, there was a trend toward an unhealthy diet in Korean adults. Our findings also suggest dietary inequalities among age, sex, and income groups, suggesting the need for more intense interventions targeting the vulnerable populations.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.