Background: Vitamin D deficiency has been linked to increased risks of fractures and cardiovascular (CV) events, but the clinical relevance of the ‘insufficiency’ range remains unclear. We investigated CV and fracture risks across vitamin D levels, with a focus on the insufficiency range. Methods: Using UK Biobank data, we analyzed 375,044 participants aged 40 to 69 years. Vitamin D status was categorized as deficient (<50 nmol/L), insufficient (≥50 to <75 nmol/L), or sufficient (≥75 nmol/L). Outcomes included three-point major adverse cardiovascular events (3P-MACE; myocardial infarction, stroke, and CV mortality) and major osteoporotic fractures, assessed via hospital records, registries, and death certificates. Results: The vitamin D-deficient group had an increased risk of CV events (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.11 to 1.24) and fractures (aHR, 1.09; 95% CI, 1.01 to 1.18) compared to the vitamin D-sufficient group. Within the deficient group, the severely deficient group (<30 nmol/L) exhibited a markedly higher risk (aHR, 1.29; 95% CI, 1.21 to 1.37 for 3PMACE; and aHR, 1.20; 95% CI, 1.10 to 1.32 for fractures). In contrast, the vitamin D-insufficient group (50 to 75 nmol/L) showed no significant increase in the risk of either outcome, with no clear benefit or harm observed. Spline curve analysis revealed a negative correlation between vitamin D levels and risk, which was observed only within the deficient range and not within the insufficient range. Conclusion Vitamin D deficiency is strongly associated with increased CV disease and fracture risks, whereas the insufficiency range shows no significant risk or benefit, raising questions about its clinical relevance.

Purpose: Lidocaine, a type of local anesthetic, is used widely to suppress pain during intra-articular injections, but many studies have suggested that lidocaine is toxic to the articular cartilage. This study examined the biological changes that occur when chondrocytes are exposed to lidocaine to determine the protective effect of human placenta hydrolysate (HPH) on chondrocytes. Materials and Methods: SW1353 cells, human-derived chondrocytes, were treated with lidocaine and HPH to confirm the changes in cell viability, production of reactive oxygen species, and MMP13 and BNIP3 gene expression levels. In addition, the radical scavenging ability of HPH was evaluated using an ABTS assay. Results: After treating the cells with the test substance for 72 hours, the cell viability increased by up to 28% in the HPH/lidocaine-treated group compared to the lidocaine-treated group. The level of reactive oxygen species, which was increased by lidocaine, was lower in the group treated with HPH/lidocaine. In addition, the expression levels of the MMP13 gene, which damages cartilage tissue, and the BNIP3 gene, which is involved in mitophagy, were also 21% and 69% lower, respectively, in the HPH/lidocaine-treated group than in the lidocainetreated group. Conclusion HPH may alleviate the side effects of an intra-articular injection of lidocaine by suppressing cell death, suppressing free radicals, and alleviating intracellular mitochondrial damage.

Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer CellFree Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. Conclusions Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

External quality assessment (EQA) trials for newborn screening tests were conducted twice in 2022 and 2023. These included tests for congenital hypothyroidism, adrenal hyperplasia, and galactosemia, as well as tandem mass spectrometry-based screenings for conditions such as phenylketonuria, maple syrup urine disease, homocystinuria. Each trial involved the analysis of six dried blood spot specimens for each test item across 15 laboratories.The mean, standard deviation, median, minimum and maximum values, and cut-offs were determined for each analyte in the newborn screening tests.The proportion of correct answers was 93%–100%. Additionally, EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, homovanillic acid, catecholamines, metanephrines, amino acids, and organic acids were performed using three specimens per trial. A well-designed EQA program, combined with continuous education, can help improve the performance of newborn screening and metabolite testing.

Background/Aims: Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI. Methods: A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups. Results: The percentage change of LDL-C level at 1–3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1–3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001). Conclusions Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known.Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVAinduced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

Purpose: This study aimed to assess the survival rate (SR) and death risk for associated pulmonary arterial hypertension (aPAH; 10th revision of the International Statistical Classification of Diseases [ICD-10], I27.2) in Koreans. Methods: The data were collected from the Korean National Health Insurance Service from 2006 through 2017 (n= 15,448). We analyzed the SR using the Kaplan-Meier method and carried out Cox proportional hazards analyses. Results: Patients’ mean age upon aPAH diagnosis was 60.1±24.0 years, and 60.7% of the patients were female. The 10-year SR of aPAH was 46.3% (95% confidence interval, 45.0 to 47.6). The factors associated with an increase in the adjusted death risk included age of 0 to 9 years, advancing age, male sex, lower income level, and comorbidities including diabetes mellitus, myocardial infarction, heart failure, hemorrhagic stroke, chronic kidney disease, malignant neoplasm, hereditary hemorrhagic telangiectasia, and systemic lupus erythematosus. Conclusion The 10-year SR of aPAH was over 46%. The risk of death from aPAH was significantly higher with advancing age, sex, lower income level, and comorbidities.