Background: The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics. Methods: We established the CBA using HEK 293 cells transiently overexpressing fulllength human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD). Results: Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ = 0.883, P < 0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r = 0.663, P < 0.001). The commercial MOG-Ab CBA kit showed one falsenegative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD. Conclusions The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. Tomitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. No-tably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Purpose: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. Methods: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. Results: After propensity score matching, 95 patients who underwent IBR following SSM/ NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5–181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. Conclusion Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

In children and adolescents, dental age estimation is performed with the development of the teeth. Various statistical analysis methods have been used to determine the relationship between age and dental maturity and develop an accurate method of age calculation. This study attempted to apply a neural network model for the statistical analysis of dental age estimation in children and evaluated its applicability. This study used 1196 panoramic radiographs of patients aged 3–16 years, and 996 and 200 were randomly classified into training and test sets, respectively. The dental maturity of the mandibular left teeth was evaluated using Demirjian's method, the neural network model using the backpropagation algorithm was derived using training sets, and the errors were evaluated using 100 radiographs of each male and female as test sets. In addition, multiple linear regression analysis was conducted on the same training set, and the error was calculated by applying it to the test set and comparing it with the error of the neural network model. In the neural network model, the mean absolute error (MAE) and root mean squared error (RMSE) were 0.589 and 0.783 in male subjects and 0.529 and 0.760 in female subjects, respectively. In the multiple linear regression model, the MAE and RMSE were 0.600 and 0.748 in male subjects and 0.566 and 0.789 in female subjects, respectively. When applying the neural network model to the statistical analysis of the dental developmental stage, the results were as accurate as those of conventional statistical analysis methods. This study’s approach is expected to be useful for estimating the ages of children.

Background: Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. Objectives: We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. Methods: Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. Results: After exposure to CA and NaOCl, body weight loss was observed but recovered.Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. Conclusions The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.

Background: Fameyes (a mixture of Clematis mandshurica Rupr. extract (CMRE) and Erigeron annuus (L.) Pers. extract (EAPE)) containing scutellarin and chlorogenic acid as major components has been reported to relieve mental stress in human subjects, which is reflected in improved scores in psychometric tests measuring levels of depression, anxi‑ ety, well-being, and mental fitness. The aim of this study was to examine the anti-stress activity of Fameyes and to investigate the mechanisms of the anti-stress activity using in vitro and in vivo models of stresses. Results: First, we tested the effect of Fameyes on corticosterone-induced cytotoxicity in SH-SY5Y cells (human neurofibroma cell lines). Corticosterone induced apoptosis and decreased cell viability and mitochondrial membrane potential, but treatment with Fameyes inhibited these cytotoxic effects in a dose-dependent manner. However, CMRE and EAPE (components of Fameyes) did not inhibit the cytotoxic effect of corticosterone individually. Next, we tested the effects of Fameyes on rats that were exposed to different kinds of stresses for four weeks. When the stressed rats were treated with Fameyes, their immobility time in forced swim and tail suspension tests decreased. A reduction was also observed in the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone. Furthermore, upon oral administration of Fameyes, serum serotonin levels increased. These in vitro and in vivo results support the anti-stress effects of Fameyes. Conclusions In vitro experiments showed anti-stress effects of Fameyes in cell viability, apoptosis, and mitochon‑ drial membrane potential. In addition, in vivo experiments using rats showed anti-stress effects of Fameyes in blood and tissue levels of ACTH, corticosterone, and serotonin, as well as the immobility time in the forced swim and tail sus‑ pension tests. However, we did not specifically investigate which ingredient or ingredients showed anti-stress effects, although we reported that Fameyes contained chlorogenic acid and scutellarin major ingredients.

Background: A rapid response system (RRS) contributes to the safety of hospitalized patients. Clinical deterioration may occur in the general ward (GW) or in non-GW locations such as radiology or dialysis units. However, there are few studies regarding RRS activation in non-GW locations. This study aimed to compare the clinical characteristics and outcomes of patients with RRS activation in non-GW locations and in the GW. Methods: From January 2016 to December 2017, all patients requiring RRS activation in nine South Korean hospitals were retrospectively enrolled and classified according to RRS activation location: GW vs non-GW RRS activations. Results: In total, 12,793 patients were enrolled; 222 (1.7%) were non-GW RRS activations.There were more instances of shock (11.6% vs. 18.5%) and cardiac arrest (2.7% vs. 22.5%) in non-GW RRS activation patients. These patients also had a lower oxygen saturation (92.6% ± 8.6% vs. 88.7% ± 14.3%, P < 0.001) and a higher National Early Warning Score 2 (7.5 ± 3.4 vs. 8.9 ± 3.8,P < 0.001) than GW RRS activation patients. Although non-GW RRS activation patients received more intubation (odds ratio [OR], 3.135; P < 0.001), advanced cardiovascular life support (OR, 3.912; P < 0.001), and intensive care unit transfer (OR, 2.502;P < 0.001), their hospital mortality (hazard ratio, 0.630; P = 0.013) was lower than GW RRS activation patients upon multivariate analysis. Conclusion Considering that there were more critically ill but recoverable cases in non-GW locations, active RRS involvement should be required in such locations.