Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Background: Renal replacement therapy (RRT) is an important treatment option for sepsisassociated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies. Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsisassociated AKI, respectively. Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsisassociated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3–25) and vasopressor administration (median, 21; IQR, 5–26) than the late CKRT group did (median, 10.5; IQR, 0–23; P = 0.037 and median, 13.5;IQR, 0–25; P = 0.028, respectively). The Kaplan–Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040).In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237). Conclusion Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.

Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist’s perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.

Background: Renal replacement therapy (RRT) is an important treatment option for sepsisassociated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies. Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsisassociated AKI, respectively. Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsisassociated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3–25) and vasopressor administration (median, 21; IQR, 5–26) than the late CKRT group did (median, 10.5; IQR, 0–23; P = 0.037 and median, 13.5;IQR, 0–25; P = 0.028, respectively). The Kaplan–Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040).In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237). Conclusion Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours.

Purpose: This report offers a detailed examination of the inception and current state of the Heavy-ion Therapy Center (HITC) at the Yonsei Cancer Center (YCC), setting it apart as the world’s first center equipped with a fixed beam and two superconducting gantries for carbon-ion radiation therapy (CIRT). Materials and Methods: Preparations for CIRT at YCC began in 2013; accordingly, this center has completed a decade of meticulous planning and culminating since the operational commencement of the HITC in April 2023. Results: This report elaborates on the clinical preparation for adopting CIRT in Korea. It includes an extensive description of HITC’s facility layout at YCC, which comprises the accelerator and treatment rooms. Furthermore, this report delineates the clinical workflow, criteria for CIRT application, and the rigorous quality assurance processes implemented at YCC. It highlights YCC’s sophisticated radiation therapy infrastructure, collaborative initiatives, and the efficacious treatment of >200 prostate cancer cases utilizing CIRT. Conclusion This manuscript concludes by discussing the prospective influence of CIRT on the medical domain within Korea, spotlighting YCC’s pioneering contribution and forecasting the widespread integration of this groundbreaking technology.