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: 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.

Background: Light-emitting diode (LED)-based photobiomodulation is used as an inducer of cell regeneration. Although numerous in vitro and in vivo orthopedic studies have been conducted, the ideal LED wavelength range for tendon healing has not yet been determined. This study, thus, focused on the effects of LED of a 630 nm wavelength on the cell viability, proliferation, and migration of human biceps tendon fibroblast cells. Methods: Human tendon fibroblast cell culture was performed using the biceps tendon of patients who had undergone biceps tenodesis. Human biceps tendon fibroblasts from two patients (male, aged 42 and 69 years) were isolated and cultured. The cell type was confirmed by a morphological analysis and using tendon and fibroblast specific markers. They were then split into three groups, with each receiving a different irradiation treatment: no LED treatment (control), 630 nm LED, and 630 nm + 880 nm LED for 20 minutes each. After the LED treatment, cell viability, proliferation, and migration assays were performed, and the results were compared between the groups. Results: Twenty-four hours after LED treatment, cell viability and proliferation were significantly increased in the 630 nm LED and 630 nm + 880 nm LED treatment groups compared to that in the control group (p < 0.05). Under the same conditions, compared with the control group, the 630 nm LED alone treatment group showed a 3.06 ± 0.21 times higher cell migration rate (p < 0.05), and the 630 nm + 880 nm LED combination treatment group showed a 2.88 ± 0.20 times higher cell migration rate (p < 0.05) in threedimensional migration assay. Conclusions In human tendon fibroblast cells, 20 minutes of LED treatment at 630 nm and 630 nm + 880 nm exhibited significant effects on cell proliferation and migration. Our findings suggest the potential of LED therapy as an adjuvant treatment for tendon healing, and hence, further research is warranted to standardize the various parameters to further develop and establish this as a reliable treatment regimen.

Background: The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. Methods: We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. Results: We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. Conclusions Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL–COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL–COL ball. CONCLUSION Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.

Background: Obstructive sleep apnea (OSA) is closely related to maternal obesity in pregnant women, and the association increases with later pregnancy. Obesity and OSA are risk factors of pregnancy-related complications, including gestational hypertension, gestational diabetes mellitus (GDM), and fetal morbidities. We aimed to determine the prevalence of OSA and to assess the impact of OSA on pregnancy-related disorders in overweight pregnant women. Methods: Eligible participants who were overweight [body mass index (BMI) ≥ 23 kg/m 2 ] in gestational age 30 weeks or more, assessed OSA using a portable polysomnography at home.Clinical data were collected from pregnant women and their babies. Results: The average age of 51 participants was 34.5 years (27–44 years). The number of primipara was 25 (49%) and that of multipara was 26 (51%). Eight cases of GDM (15.7%) and five cases of preeclampsia (9.8%) were reported, and six patients (11.8%) experienced preterm delivery. In results of polysomnography, 14 patients (27.5%) were diagnosed as OSA. Apnea-hypopnea index moderately correlated with BMI (r = 0.515, P < 0.001). The BMI (P < 0.005) and preeclampsia rate (P < 0.017) were higher in the OSA group compared to the control group. Odds ratios (ORs) adjusting age, BMI, parity, and abortion history were calculated. The presence of OSA increased OR of preeclampsia (OR, 13.1; 95% confidence interval, 1.1–171.3). The majority of preeclampsia patients (4/5, 80%) underwent preterm delivery. Conclusion OSA is an important risk factor for preeclampsia, resulting in preterm delivery.For overweight pregnant women, an OSA evaluation should be mandatory.

Purpose: We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. Materials and Methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. Results: A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. Conclusion This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

Purpose: The aim of this study was to show that bariatric surgery (BS) is more effective than medical therapy (MT) in Asian obese patients. Methods: In this prospective, multicenter, nonrandomized, controlled trial, obese patients with body mass index of ≥35 kg/m2 or 30.0–34.9 kg/m2 with obesity-related comorbidities were assigned to undergo BS, such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, or MT. Patients who underwent BS were evaluated 4, 12, 24, and 48 weeks after surgery, whereas patients who received MT were monitored at a hospital every 6 weeks for 1 year. At each visit, weight, waist and hip circumference, and blood pressure were measured, and patients underwent physical examination and laboratory testing. Health-related quality of life (HQOL) was investigated using Euro QOL-5 Dimension, Impact of Weight on Quality of Life questionnaire-Lite and Obesity-related Problems scale. Results: The study included 264 patients from 13 institutions; of these, 64 underwent BS and 200 received MT. Of the patients who underwent BS, 6.3% experienced early complications. Relative weight changes from baseline to 48 weeks were significantly greater in the BS than in the MT group (26.9% vs. 2.1%, P < 0.001), as were the rates of remission of diabetes (47.8% vs. 16.7%, P = 0.014), hypertension (60.0% vs. 26.1%, P < 0.001), and dyslipidemia (63.2% vs. 22.0%, P < 0.001). HQOL was better in the BS than in the MT group at 48 weeks. Conclusion BS was safe and effective in Korean obese patients, with greater weight reduction, remission of comorbidities, and quality of life improvement than MT.