Background: The heart donor allocation system in South Korea is divided into three regions, with priority given to recipients within the same region over those in other regions of the same tier. It is commonly believed that heart transplantation (HT) within the same region can reduce ischemic time (IT), although its clinical impact remains unclear. The purpose of this study is to compare the characteristics and outcomes of intra-region HT and inter-region HT. Methods: From 2014 to 2022, a total of 115 adult patients underwent isolated HT at a tertiary hospital. Of these, 58 recipients (54.5 ± 10.3 years, female, 36.2%) underwent intra-region HT and 57 recipients (53.9 ± 14.1 years, female, 31.6%) underwent inter-region HT. Extracorporeal membrane oxygenation-bridged HTs accounted for 50.0% and 54.4% of cases, respectively (P = 0.638). There were no differences in preoperative characteristics between the two groups. Results: The median inter-hospital distance (38.0 [32.0–112.0] km vs. 351.0 [300.0–390.5] km, P < 0.001) and total IT (153 [123–170] minute vs. 265 [243–298] minute, P < 0.001) were longer in the inter-region group than intra-region group. Despite these differences, both groups showed similar clinical outcomes. The 30-day mortality rates were 5.2% and 5.3% (P < 0.99), respectively. There were no differences in postoperative cardiac index, early adverse outcomes, or long-term survival between the two groups. The inter-hospital distance and cold IT showed a strong positive correlation (time [minute] = 39.462 + 0.410 × distance [km]). Conclusion Despite the difference in IT, there was no difference in postoperative outcomes between the two groups. Based on these findings, the effect of donor location on the outcomes of HT in South Korea is not considered significant.

Background: The heart donor allocation system in South Korea is divided into three regions, with priority given to recipients within the same region over those in other regions of the same tier. It is commonly believed that heart transplantation (HT) within the same region can reduce ischemic time (IT), although its clinical impact remains unclear. The purpose of this study is to compare the characteristics and outcomes of intra-region HT and inter-region HT. Methods: From 2014 to 2022, a total of 115 adult patients underwent isolated HT at a tertiary hospital. Of these, 58 recipients (54.5 ± 10.3 years, female, 36.2%) underwent intra-region HT and 57 recipients (53.9 ± 14.1 years, female, 31.6%) underwent inter-region HT. Extracorporeal membrane oxygenation-bridged HTs accounted for 50.0% and 54.4% of cases, respectively (P = 0.638). There were no differences in preoperative characteristics between the two groups. Results: The median inter-hospital distance (38.0 [32.0–112.0] km vs. 351.0 [300.0–390.5] km, P < 0.001) and total IT (153 [123–170] minute vs. 265 [243–298] minute, P < 0.001) were longer in the inter-region group than intra-region group. Despite these differences, both groups showed similar clinical outcomes. The 30-day mortality rates were 5.2% and 5.3% (P < 0.99), respectively. There were no differences in postoperative cardiac index, early adverse outcomes, or long-term survival between the two groups. The inter-hospital distance and cold IT showed a strong positive correlation (time [minute] = 39.462 + 0.410 × distance [km]). Conclusion Despite the difference in IT, there was no difference in postoperative outcomes between the two groups. Based on these findings, the effect of donor location on the outcomes of HT in South Korea is not considered significant.

Background: The heart donor allocation system in South Korea is divided into three regions, with priority given to recipients within the same region over those in other regions of the same tier. It is commonly believed that heart transplantation (HT) within the same region can reduce ischemic time (IT), although its clinical impact remains unclear. The purpose of this study is to compare the characteristics and outcomes of intra-region HT and inter-region HT. Methods: From 2014 to 2022, a total of 115 adult patients underwent isolated HT at a tertiary hospital. Of these, 58 recipients (54.5 ± 10.3 years, female, 36.2%) underwent intra-region HT and 57 recipients (53.9 ± 14.1 years, female, 31.6%) underwent inter-region HT. Extracorporeal membrane oxygenation-bridged HTs accounted for 50.0% and 54.4% of cases, respectively (P = 0.638). There were no differences in preoperative characteristics between the two groups. Results: The median inter-hospital distance (38.0 [32.0–112.0] km vs. 351.0 [300.0–390.5] km, P < 0.001) and total IT (153 [123–170] minute vs. 265 [243–298] minute, P < 0.001) were longer in the inter-region group than intra-region group. Despite these differences, both groups showed similar clinical outcomes. The 30-day mortality rates were 5.2% and 5.3% (P < 0.99), respectively. There were no differences in postoperative cardiac index, early adverse outcomes, or long-term survival between the two groups. The inter-hospital distance and cold IT showed a strong positive correlation (time [minute] = 39.462 + 0.410 × distance [km]). Conclusion Despite the difference in IT, there was no difference in postoperative outcomes between the two groups. Based on these findings, the effect of donor location on the outcomes of HT in South Korea is not considered significant.

Background: The heart donor allocation system in South Korea is divided into three regions, with priority given to recipients within the same region over those in other regions of the same tier. It is commonly believed that heart transplantation (HT) within the same region can reduce ischemic time (IT), although its clinical impact remains unclear. The purpose of this study is to compare the characteristics and outcomes of intra-region HT and inter-region HT. Methods: From 2014 to 2022, a total of 115 adult patients underwent isolated HT at a tertiary hospital. Of these, 58 recipients (54.5 ± 10.3 years, female, 36.2%) underwent intra-region HT and 57 recipients (53.9 ± 14.1 years, female, 31.6%) underwent inter-region HT. Extracorporeal membrane oxygenation-bridged HTs accounted for 50.0% and 54.4% of cases, respectively (P = 0.638). There were no differences in preoperative characteristics between the two groups. Results: The median inter-hospital distance (38.0 [32.0–112.0] km vs. 351.0 [300.0–390.5] km, P < 0.001) and total IT (153 [123–170] minute vs. 265 [243–298] minute, P < 0.001) were longer in the inter-region group than intra-region group. Despite these differences, both groups showed similar clinical outcomes. The 30-day mortality rates were 5.2% and 5.3% (P < 0.99), respectively. There were no differences in postoperative cardiac index, early adverse outcomes, or long-term survival between the two groups. The inter-hospital distance and cold IT showed a strong positive correlation (time [minute] = 39.462 + 0.410 × distance [km]). Conclusion Despite the difference in IT, there was no difference in postoperative outcomes between the two groups. Based on these findings, the effect of donor location on the outcomes of HT in South Korea is not considered significant.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Objective: : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods: : Twenty-eight female Wistar rats (250–300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson’s trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results: : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson’s trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.