Background: Acute deterioration of patients in general wards often leads to major adverse events (MAEs), including unplanned intensive care unit transfers, cardiac arrest, or death. Traditional early warning scores (EWSs) have shown limited predictive accuracy, with frequent false positives. We conducted a prospective observational external validation study of an artificial intelligence (AI)-based EWS, the VitalCare - Major Adverse Event Score (VC-MAES), at a tertiary medical center in the Republic of Korea. Methods: Adult patients from general wards, including internal medicine (IM) and obstetrics and gynecology (OBGYN)—the latter were rarely investigated in prior AI-based EWS studies—were included. The VC-MAES predictions were compared with National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) predictions using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and logistic regression for baseline EWS values. False-positives per true positive (FPpTP) were assessed based on the power threshold. Results: Of 6,039 encounters, 217 (3.6%) had MAEs (IM: 9.5%, OBGYN: 0.26%). Six hours prior to MAEs, the VC-MAES achieved an AUROC of 0.918 and an AUPRC of 0.352, including the OBGYN subgroup (AUROC, 0.964; AUPRC, 0.388), outperforming the NEWS (0.797 and 0.124) and MEWS (0.722 and 0.079). The FPpTP was reduced by up to 71%. Baseline VC-MAES was strongly associated with MAEs (P<0.001). Conclusions The VC-MAES significantly outperformed traditional EWSs in predicting adverse events in general ward patients. The robust performance and lower FPpTP suggest that broader adoption of the VC-MAES may improve clinical efficiency and resource allocation in general wards.

Background: MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available. Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen. Results: The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520. Conclusions This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

Background: An international reference measurement laboratory network for creatinine (Cr) is lacking; therefore, Korea developed an independent evaluation and certification system. The in vitro diagnostics (IVD) certification program, launched in 2017, formed part of a broader Cr standardization initiative intended to enhance accuracy at the manufacturing stage. Methods: The program was designed to evaluate analytical systems, including all reagent lots, calibrators, and instrument models, twice annually. Bias, imprecision, total error (TE), and linearity were evaluated based on established acceptance criteria. A post-certification process allows submission for a second challenge and validation of corrective actions. Results: Between 2017 and 2023, 489 analytical systems were evaluated. Average acceptance rates for bias, imprecision, TE, and linearity were 70.8%, 95.9%, 87.7%, and 87.8%, respectively. The lowest acceptance rate for bias evaluation was 8.7% for the kinetic Jaffe method without compensation in 2018. Over the 7-year period, the mean absolute percentage bias (absBias%), coefficient of variation (CV), and TE were 4.62%, 1.37%,and 7.29%, respectively. The highest absBias% (7.94%) was observed in the 0.0 ≤ Cr < 1.0target value range. Since 2019, a consistent reduction in absBias% has been observed. Conclusions This program is a pioneering response to the absence of a global certification program for Cr assays. It offers significant advantages, including comprehensive evaluations, fee-free participation, and a robust post-certification process. Continuous participation and improvement efforts by manufacturers have contributed to enhanced accuracy in Cr assays.

A comprehensive list of occupational diseases among farmers is crucial for both compensation and prevention efforts. In Korea, most farmers are self-employed, and some occupational diseases are compensated through farmer safety insurance. However, it is not harmonized with industrial accident compensation insurance and does not adequately reflect the true burden of occupational diseases among farmers. To address this gap, the authors compiled a list of occupational diseases tailored to Korean farmers by reviewing the International Labor Organization’s list of occupational diseases, the Korean Industrial Accident Compensation Insurance List, the occupational disease lists of other countries, and relevant literature on farmers’ work-related diseases.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Purpose: Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM. Methods: Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated. Results: In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations. Conclusion The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.