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: 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: 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: Tacrolimus is a key immunosuppressant after liver transplantation.Although guideline-recommended trough levels are 4–10 ng/mL, concerns about nephrotoxicity, metabolic complications, and malignancies have led to interest in minimizing tacrolimus use. However, the effects of lower tacrolimus levels on graft rejection and hepatocellular carcinoma (HCC) recurrence remain unclear. Methods: We conducted a single-center, retrospective study of adult patients (≥19 years) who underwent living donor liver transplantation between January 2000 and December 2021. Patients were divided into low tacrolimus (FK) (<6 ng/mL) and high FK (≥6 ng/mL) groups based on tacrolimus levels measured 1–2 years post-transplantation. We analyzed overall survival, biopsy-proven rejection-free survival, and HCC recurrence-free survival in relevant subgroups. Cox proportional hazards regression identified predictors of mortality, rejection, and HCC recurrence. Results: Among 1,117 recipients, 941 were in the low FK group and 176 in the high FK group. Landmark analysis showed significantly better 10-year overall survival in the low FK group (82.8% vs. 68.8%, p=0.016), while rejection-free survival did not differ significantly beyond 2 years (p=0.098), despite early separation favoring the low FK group (p<0.001). Higher tacrolimus levels independently predicted increased mortality (hazard ratio [HR]=1.98, 95% confidence interval [CI] 1.35–2.89; p<0.001) and rejection (HR=2.20, 95% CI 1.48–3.27; p<0.001). Among 614 HCC patients, landmark analysis revealed no significant difference in recurrence-free survival (77.7% vs. 81.2%, p=0.288) or overall survival (77.3% vs. 65.8%, p=0.215), and FK levels were not independently associated with either outcome. Conclusion Maintaining tacrolimus levels below 6 ng/mL was associated with better survival and rejection outcomes without increasing HCC recurrence, suggesting dose minimization may be feasible in selected patients.

Purpose: Radiographic examinations are frequently performed for diagnostic and therapeutic purposes in neonatal intensive care units (NICUs). However, concerns are emerging regarding the safety of radiation exposure, especially in vulnerable preterm infants in periods of rapid cellular division. This quality improvement (QI) project aimed to reduce radiation hazards in level-IV NICU. Methods: We established an "X-ray prescription protocol" and educated the physicians to ensure that only essential radiographs were obtained. Additionally, we discouraged full-body infantograms and emphasized the prescription of targeted radiographs, such as chest or abdominal radiographs. Furthermore, to reduce the dose-area product (DAP, Gy·cm2) values, which act as a surrogate for radiation exposure, we provided training to radiologic technologists on meticulous collimation for each radiography session. We aimed to achieve a 30% reduction in the average monthly cumulative DAP per patient, which was calculated by dividing the total monthly DAP from radiographs in the NICU by the monthly average of patient admissions. Retrospective baseline data were collected 8 months pre-intervention and prospectively for 4 months post-interventions. Results: The average monthly X-ray count per patient was 28.3 in the pre-intervention period (October 2022 to May 2023), which decreased to 25.4 in the post-intervention period (June 2023 to September 2023), reflecting a 10.2% reduction (p=0.109). The average monthly infantogram count per patient showed an 18.0% reduction (25.9% to 21.2%, p=0.016), and the proportion of infantograms in the total X-ray counts decreased from 91.5% to 83.3% (p=0.017). The DAP value per X-ray decreased by 42.6%, from an average of 0.25 to 0.14 (p=0.011). The primary outcome, the average monthly cumulative DAP value per patient, showed a substantial reduction of 48.6%, dropping from 7.00 to 3.60 (p=0.004). The baseline characteristics and short-term morbidities of the patients did not differ significantly between the pre- and post-intervention period. Conclusion Our QI approach, which included discouraging excessive prescriptions of infantograms and promoting optimal collimation, significantly reduced the average monthly radiation exposure in the NICU, benefiting both patients and healthcare workers.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Purpose: Radiographic examinations are frequently performed for diagnostic and therapeutic purposes in neonatal intensive care units (NICUs). However, concerns are emerging regarding the safety of radiation exposure, especially in vulnerable preterm infants in periods of rapid cellular division. This quality improvement (QI) project aimed to reduce radiation hazards in level-IV NICU. Methods: We established an "X-ray prescription protocol" and educated the physicians to ensure that only essential radiographs were obtained. Additionally, we discouraged full-body infantograms and emphasized the prescription of targeted radiographs, such as chest or abdominal radiographs. Furthermore, to reduce the dose-area product (DAP, Gy·cm2) values, which act as a surrogate for radiation exposure, we provided training to radiologic technologists on meticulous collimation for each radiography session. We aimed to achieve a 30% reduction in the average monthly cumulative DAP per patient, which was calculated by dividing the total monthly DAP from radiographs in the NICU by the monthly average of patient admissions. Retrospective baseline data were collected 8 months pre-intervention and prospectively for 4 months post-interventions. Results: The average monthly X-ray count per patient was 28.3 in the pre-intervention period (October 2022 to May 2023), which decreased to 25.4 in the post-intervention period (June 2023 to September 2023), reflecting a 10.2% reduction (p=0.109). The average monthly infantogram count per patient showed an 18.0% reduction (25.9% to 21.2%, p=0.016), and the proportion of infantograms in the total X-ray counts decreased from 91.5% to 83.3% (p=0.017). The DAP value per X-ray decreased by 42.6%, from an average of 0.25 to 0.14 (p=0.011). The primary outcome, the average monthly cumulative DAP value per patient, showed a substantial reduction of 48.6%, dropping from 7.00 to 3.60 (p=0.004). The baseline characteristics and short-term morbidities of the patients did not differ significantly between the pre- and post-intervention period. Conclusion Our QI approach, which included discouraging excessive prescriptions of infantograms and promoting optimal collimation, significantly reduced the average monthly radiation exposure in the NICU, benefiting both patients and healthcare workers.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: Radiographic examinations are frequently performed for diagnostic and therapeutic purposes in neonatal intensive care units (NICUs). However, concerns are emerging regarding the safety of radiation exposure, especially in vulnerable preterm infants in periods of rapid cellular division. This quality improvement (QI) project aimed to reduce radiation hazards in level-IV NICU. Methods: We established an "X-ray prescription protocol" and educated the physicians to ensure that only essential radiographs were obtained. Additionally, we discouraged full-body infantograms and emphasized the prescription of targeted radiographs, such as chest or abdominal radiographs. Furthermore, to reduce the dose-area product (DAP, Gy·cm2) values, which act as a surrogate for radiation exposure, we provided training to radiologic technologists on meticulous collimation for each radiography session. We aimed to achieve a 30% reduction in the average monthly cumulative DAP per patient, which was calculated by dividing the total monthly DAP from radiographs in the NICU by the monthly average of patient admissions. Retrospective baseline data were collected 8 months pre-intervention and prospectively for 4 months post-interventions. Results: The average monthly X-ray count per patient was 28.3 in the pre-intervention period (October 2022 to May 2023), which decreased to 25.4 in the post-intervention period (June 2023 to September 2023), reflecting a 10.2% reduction (p=0.109). The average monthly infantogram count per patient showed an 18.0% reduction (25.9% to 21.2%, p=0.016), and the proportion of infantograms in the total X-ray counts decreased from 91.5% to 83.3% (p=0.017). The DAP value per X-ray decreased by 42.6%, from an average of 0.25 to 0.14 (p=0.011). The primary outcome, the average monthly cumulative DAP value per patient, showed a substantial reduction of 48.6%, dropping from 7.00 to 3.60 (p=0.004). The baseline characteristics and short-term morbidities of the patients did not differ significantly between the pre- and post-intervention period. Conclusion Our QI approach, which included discouraging excessive prescriptions of infantograms and promoting optimal collimation, significantly reduced the average monthly radiation exposure in the NICU, benefiting both patients and healthcare workers.