Background and Objectives: The Korean Organ Transplant Registry (KOTRY) provided data for this third official report on adult heart transplantation (HT), including information from 709 recipients. Methods: Data from HTs performed at seven major centers in Korea between March 2014 and December 2020 were analyzed, focusing on immunosuppression, acute rejection, cardiac allograft vasculopathy (CAV), post-transplant survival, and mechanical circulatory support (MCS) usage. Results: The median ages of the recipients and donors were 56.0 and 43.0 years, respectively.Cardiomyopathy and ischemic heart disease were the most common preceding conditions for HT. A significant portion of patients underwent HT at waiting list status 1 and 0. In the multivariate analysis, a predicted heart mass mismatch was associated with a higher risk of 1-year mortality. Patients over 70 years old had a significantly increased risk of 6-year mortality. The risk of CAV was higher for male donors and donors older than 45 years. Acute rejection was more likely in patients with panel reactive antibody levels above 80%, while statin use was associated with a reduced risk. The employment of left ventricular assist device as a bridge to transplantation increased from 2.17% to 22.4%. Pre-transplant extra-corporeal membrane oxygenation was associated with worse post-transplant survival. Conclusions In this third KOTRY report, we analyzed changes in the characteristics of adult HT recipients and donors and their impact on post-transplant outcomes. The most notable discovery was the increased use of MCS before HT and their impact on post-transplant outcomes.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies. Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed. Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05). Conclusions These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.

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.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

OBJECTIVES: Gender is a major determinant of health behaviors that influences cancer prevention awareness and practices. This study investigated the relationship of the awareness and practice rates of cancer prevention recommendations with gender and socioeconomic status. METHODS: We used data from the Korean National Cancer Prevention Awareness and Practice Survey (2023). The sample included 4,000 men and women aged 20-74 years. We conducted multiple logistic regression analyses to evaluate associations with the awareness and practices of cancer prevention, and a joinpoint regression analysis using age-standardized rates to analyze trends in awareness and practice rates from 2007 to 2023. RESULTS: The awareness rates were 79.4% and 81.2% for men and women, respectively. The overall practice rates were substantially lower (43.1% for men and 48.9% for women). For men, awareness rates did not differ significantly by socio-demographic characteristics, but practice rates increased with age (20-29: 15.9%; 60-74: 53.8%). For women, both awareness (20-29: 73.0%; 60-74: 85.7%) and practice (20-29: 16.8%; 60-74: 67.5%) rates increased with age. The easiest recommendations to follow were “reducing salt intake and avoiding burnt or charred foods” (men: 29.9%; women: 28.4%), whereas the most difficult recommendation was “engaging in regular physical activity” (men: 32.5%; women: 34.4%). CONCLUSIONS While awareness of cancer prevention recommendations was high, the practice of these recommendations was low. Gender influenced changes in awareness and practice rates over time, reflecting a large gap in practice. Future research should explore appropriate intervention points for cancer prevention practices and the development of more effective cancer prevention policies.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.