Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Background: Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways. Methods: C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed. Results: Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups. Conclusion Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.

The Pfizer-BioNTech COVID-19 vaccine has shown excellent clinical effectiveness; however, adverse events of the vaccine remain a concern in Korea. We surveyed adverse events in 2498 healthcare workers vaccinated with the Pfizer-BioNTech COVID-19 vaccine at a university hospital. The survey was conducted using a diary card for 7 days following each injection. The questionnaire response rate was 75.1% (1876/2498) for the first dose and 73.8% (1840/2493) for the second dose. Among local reactions, pain was the most commonly reported (84.9% after the first dose and 90.4% after the second dose). After the second dose, two people visited the emergency room due to severe local pain, but no hospitalization or skin necrosis occurred. Among systemic reactions, fatigue was most frequently reported (52.8% after the first dose and 77.0% after the second dose), followed by myalgia (49.0% and 76.1%), headache (28.7% and 59.2%), chills (16.7% and 54.0%), and arthralgia (11.4% and 39.2%). One or more critical adverse events occurred in 0.2% and 0.7% of the vaccinees. Except for urticaria, more adverse events were reported after the second dose than after the first dose. In the future, adverse events should be investigated in older adults, and a future study with a longer observation period should be conducted.

BACKGROUND: There has been no study on the time trends of dementia incidence in Korea. We report the 5-year incidence and its correlates of all-cause and Alzheimer's disease (AD) dementia, and compared our results with those of a 12-year-prior cohort study conducted in the same area. METHODS: A total of 751 community-dwelling older adults were followed up for a mean duration of 5.4 years. The age-, gender-, and educational attainment-specific incidence of all-cause and AD dementia were reported as cases per 1,000 person-years. We performed univariate and multivariate cox proportional hazard regression analyses to determine whether baseline sociodemographic, lifestyle, and clinical variables were associated with the risk of all-cause and AD dementia. A 12-year-prior cohort study was used for descriptive comparison to indicate the time trends of dementia incidence. RESULTS: The incidence rates were 16.2 and 13.0 cases per 1,000 person-years for all-cause and AD dementia, respectively. The baseline diagnosis of mild cognitive impairment increased the 5-year incidence of all-cause dementia by more than 4-fold. Old age and low baseline global cognitive function were noted as risk factors for both all-cause and AD dementia. CONCLUSION: Upon comparing the results with those from the earlier cohort study in Yeoncheon, the incidence of all-cause and AD dementia decreased by approximately 40% over 12 years; it has been mainly driven by the increase in the educational level of older adults. The declining time trends of incidence should be taken into account for estimating the future prevalence of dementia in Korea.
Adult ; Alzheimer Disease ; Cognition ; Cohort Studies ; Dementia ; Diagnosis ; Humans ; Incidence ; Korea ; Life Style ; Mild Cognitive Impairment ; Prevalence ; Risk Factors

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥−34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3′ overhang at the 3′ end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.
Dihydroxyphenylalanine ; Gene Expression ; Humans ; Melanins ; Melanocytes ; Melanoma ; Monophenol Monooxygenase* ; RNA ; RNA Interference ; RNA, Small Interfering* ; Skin Pigmentation ; Tyrosine ; Weights and Measures

BACKGROUND: Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone. METHODS: MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 µM), rosiglitazone (0.4 µM), or pioglitazone (1 µM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment. RESULTS: As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice. CONCLUSION: These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.
Adipogenesis ; Alkaline Phosphatase ; Animals ; Biology ; Bone and Bones ; Bone Density* ; Diabetes Mellitus, Type 2 ; Femur ; Gene Expression ; Humans ; In Vitro Techniques ; Infant ; Mice* ; Osteoblasts ; Osteocalcin ; Peroxisomes ; RNA, Messenger ; Thiazolidinediones ; Transcription Factors

Many epidemiological studies suggest that overweight is associated with an elevated risk of psychiatric disorders and suicidal tendency. However, findings vary across studies, and some have contradictory results. We investigated the relationship of overweight with a range of psychiatric disorders and suicidality in the Korean general population. A multistage cluster sampling design was adopted. A total of 6,022 participants aged 18–74 years completed face-to-face interviews (response rate: 78.7%) including assessment of psychiatric disorders, suicidality, and height and weight. Overweight (defined as body mass index of ≥ 25) was associated with an increase in the lifetime prevalence of depressive disorders (adjusted odds ratio [AOR] 1.38; 95% confidence interval [CI], 1.07–1.77), suicidal ideation (AOR, 1.42; 95% CI, 1.20–1.68), and suicidal plans (AOR, 1.44; 95% CI, 1.02–2.03), controlling for sociodemographic variables. Subgroup analysis found that the association between overweight and depressive disorders exists only in women aged 18–44 years (AOR, 1.75; 95% CI, 1.07–2.89) while the association of overweight with suicidal ideation (AOR, 2.08; 95% CI, 1.53–2.82) and suicide plans (AOR, 2.59; 95% CI, 1.25–5.37) existed only in men aged 18–44 years. Overweight was associated with increased odds of nicotine use disorders in women aged 18–44 years (AOR, 2.35; 95% CI, 1.02–5.43), but the association was in the opposite direction in men aged 45–74 years (AOR, 0.64; 95% CI, 0.43–0.94). In conclusion, overweight is related to various psychiatric disorders and suicidality in Korea. Policy makers and clinicians should pay more attention to the mental health of overweight individuals.
Administrative Personnel ; Body Mass Index ; Cross-Sectional Studies ; Depressive Disorder ; Epidemiologic Studies ; Female ; Humans ; Korea* ; Male ; Mental Disorders ; Mental Health ; Obesity ; Odds Ratio ; Overweight* ; Prevalence* ; Suicidal Ideation ; Suicide ; Tobacco Use Disorder

OBJECTIVE: There are conflicting reports about whether individual anxiety disorders are independently associated with suicidal ideation and suicide attempts. We examined whether anxiety disorders are related to suicidal ideation and suicide attempts in a community sample of South Korean adults. METHODS: In-person interviews based on the South Korean version of the Composite International Diagnostic Interview were conducted to diagnose mental disorders. Multivariate logistic regression analysis was performed to examine whether anxiety disorders were associated with suicidal ideation and suicide attempts. Each regression model treated lifetime diagnosis of anxiety disorders as independent variables. Sociodemographic characteristics, cohabitation status, lifetime history of mood disorders, alcohol use disorders, and psychotic disorders were included as covariates. RESULTS: Nationally representative sample of 6,510 South Korean adults aged 18–64 years was recruited. Multivariate analysis adjusted for psychiatric comorbidity and sociodemographic variables revealed that generalized anxiety disorder (GAD) [2.34, 95% confidence interval (CI) (1.27, 4.33)], post-traumatic stress disorder (PTSD) (3.50, 95% CI: 2.16, 5.68), specific phobia (1.55, 95% CI: 1.14, 2.11), social phobia (2.97, 95% CI: 1.27, 6.94), and obsessive-compulsive disorder (OCD) (5.58, 95% CI: 2.70, 11.6) were associated with suicidal ideation, whereas only social phobia (3.78, 95% CI: 1.41, 10.1) and PTSD (5.13, 95% CI: 2.81, 9.37) were associated with suicide attempts. CONCLUSION: Individual anxiety disorders are independently associated with suicidal ideation and/or suicide attempts. The importance of the early detection of anxiety disorders and of assessing the suicide risk in individuals with anxiety disorders is emphasized.
Adult* ; Anxiety Disorders* ; Anxiety* ; Comorbidity ; Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders* ; Humans ; Logistic Models ; Mental Disorders ; Mood Disorders ; Multivariate Analysis ; Obsessive-Compulsive Disorder ; Panic Disorder ; Phobic Disorders ; Psychotic Disorders ; Stress Disorders, Post-Traumatic ; Suicidal Ideation ; Suicide

OBJECTIVE: The aims of this study were to estimate the prevalence of mental-physical comorbidity and health-threatening risk factors in subjects with mental disorders, and the risks of mental disorders in those with physical diseases for the last 12 months in the general Korean population. METHODS: Korean Epidemiologic Catchment Area study replication (KECA-R) was conducted for 6,510 adults between August 2006 and April 2007. The Korean version of Composite International Diagnostic Interview 2.1 (K-CIDI) was used in the survey. Prevalence of mental and physical disorders, and risk factors for physical health were calculated, and their associations were evaluated with adjustment for age and sex. RESULTS: Subjects with any mental disorder showed significantly higher prevalence of chronic physical conditions (adjusted odds ratio, AOR=1.5 to 2.8, p<0.001) and medical risk factors including smoking, heavy drinking, overweight, and hypertension (AOR=1.5 to 4.0, p<0.001). Of those with chronic physical conditions, 21.6% had one or more comorbid mental disorder compared with 10.5% of the subjects without chronic physical disorders (AOR=2.6, p<0.001). Contrary to expectations, depressive disorders did not show significant association with hypertension and prevalence of obesity was not influenced by presence of mental disorders. Further studies should assess these findings. CONCLUSION: This is the first identification of significant mental-physical comorbidity in the general Korean population. Clinicians and health care officials should keep in mind of its potential adverse effects on treatment outcome and aggravated disease-related socioeconomic burden.
Adult* ; Comorbidity* ; Delivery of Health Care ; Depressive Disorder ; Drinking ; Epidemiology ; Humans ; Hypertension ; Korea* ; Mental Disorders ; Obesity ; Odds Ratio ; Overweight ; Prevalence ; Psychosomatic Medicine ; Risk Factors ; Smoke ; Smoking ; Treatment Outcome

Cavernous hemangiomas of the gastrointestinal tract are extremely rare. In particular, the diagnosis of small bowel hemangiomas is very difficult in children. A 13-year-old boy presented at the outpatient clinic with dizziness and fatigue. The patient was previously diagnosed with iron-deficiency anemia at 3 years of age and had been treated with iron supplements continuously and pure red cell transfusion intermittently. Laboratory tests indicated that the patient currently had iron-deficiency anemia. There was no evidence of gross bleeding, such as hematemesis or bloody stool. Laboratory findings indicated no bleeding tendency. Gastroduodenoscopy and colonoscopy results were negative. To obtain a definitive diagnosis, the patient underwent capsule endoscopy. A purplish stalked mass was found in the jejunum, and the mass was excised successfully. We report of a 13-year-old boy who presented with severe and recurrent iron-deficiency anemia caused by a cavernous hemangioma in the small bowel without symptoms of gastrointestinal bleeding.
Adolescent ; Ambulatory Care Facilities ; Anemia, Iron-Deficiency* ; Capsule Endoscopy* ; Child* ; Colonoscopy ; Diagnosis ; Dizziness ; Fatigue ; Gastrointestinal Tract ; Hemangioma ; Hemangioma, Cavernous* ; Hematemesis ; Hemorrhage ; Humans ; Iron ; Jejunum ; Male