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/OBJECTIVES: The doubly labeled water (DLW) method is the gold standard for estimating total energy expenditure (TEE) and is also useful for verifying the validities of dietary evaluation tools. In this study, we compared the accuracy of total energy intakes (TEI) estimated by the 24-h diet recall method with TEE obtained using the doubly labeled water method. SUBJECTS/METHODS: This study involved 71 subjects aged 20–49 yrs. Over a 14-day period, three 24-h diet recalls per subject (2 weekdays and 1 weekend day) were used to estimate energy intakes, while TEE was measured using the DLW method. The paired t-test was used to determine the significance of differences between TEI and TEE results, and the accuracy of the 24-h recall method was determined by accuracy predictions percentage, root mean square error, and bias. RESULTS: Average study subject age was 33.4 ± 8.6 yrs. The association between TEI and TEE was positive and significant (r = 0.463, P < 0.001), and the difference between TEI (2,084.3 ± 684.2 kcal/day) and TEE (2,401.7 ± 480.3 kcal/day) was also significant (P < 0.001). In all study subjects, mean TEI was 12.0% (307.5 ± 629.3 kcal/day) less than mean TEE, and 12.2% (349.4 ± 632.5 kcal/day) less in men and 11.8% (266.7 ± 632.5 kcal/day) less in women. Rates of TEI underprediction for all study subjects, men, and women, were 60.5%, 51.4%, and 66.7%, respectively. CONCLUSIONS This study shows that 24-h diet recall underreports energy intakes. More research is needed to corroborate our findings and evaluate the accuracy of 24-h recall with respect to additional demographics.

PURPOSE: We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. MATERIALS AND METHODS: Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. RESULTS: Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. CONCLUSIONS: Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model.
Angelica* ; Animals ; Epididymis ; Epimedium* ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone* ; Humans ; Infertility, Male* ; Lutein* ; Luteinizing Hormone ; Male ; Male* ; Models, Animal* ; Oxidative Stress ; Rats* ; Rats, Sprague-Dawley ; Sperm Count ; Spermatogenesis* ; Spermatozoa ; Superoxide Dismutase ; Testis ; Testosterone ; Water

BACKGROUND/OBJECTIVES: The doubly labeled water (DLW) method is considered the gold standard for the measurement of total energy expenditure (TEE), which serves to estimate energy requirements. This study evaluated the accuracy of predictive dietary reference intake (DRI) equations for determining the estimated energy requirements (EER) of Korean adults by using the DLW as a reference method. SUBJECTS/METHODS: Seventy-one participants (35 men and 36 women) aged between 20 and 49 years were included in the study. The subjects' EER, calculated by using the DRI equation (EER(DRI)), was compared with their TEE measured by the DLW method (TEE(DLW)). RESULTS: The DRI equations for EER underestimated TEE by -36.3 kcal/day (-1.3%) in men and -104.5 kcal/day (-4.9%) in women. The percentages of accurate predictions among subjects were 77.1% in men and 62.9% in women. There was a strong linear correlation between EER(DRI) and TEE(DLW) (r=0.783, P<0.001 in men and r=0.810, P<0.001 in women). CONCLUSIONS: The present study supports the use of DRI prediction equations to determine EER in Korean adults. More studies are needed to confirm our results and to assess the validity of these equations in other population groups, including children, adolescents, and older adults.
Adolescent ; Adult* ; Child ; Energy Metabolism ; Female ; Humans ; Male ; Methods* ; Nutritional Requirements ; Population Groups ; Recommended Dietary Allowances* ; Water*

BACKGROUND/AIMS: This study compared the clinical benefits of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) with pemetrexed to identify the clinical parameters that correlated with response. METHODS: A retrospective chart review examined patients who were 1) treated with EGFR TKI or pemetrexed, 2) diagnosed with advanced non-squamous non-small-cell lung cancer, and 3) previously treated with platinum-based chemotherapy in Soonchunhyang Bucheon Hospital. RESULTS: Sixty-one patients (18 erlotinib, 18 gefitinib, 25 pemetrexed) were investigated from February 2002 to August 2009. The median follow-up period was 37 months (7~97 months). Overall, their median age was 63 years, 41 patients were non-smokers, 57 patients had adenocarcinoma, and 55 patients were at stage IV. Twenty-one patients received the study drugs as second-line chemotherapy, and others as third-line or more. No significant differences in the overall response rate (erlotinib 33.3% vs. gefitinib 38.9% vs. pemetrexed 20.0%) and progression-free survival (erlotinib 1.9 months vs. gefitinib 3.0 months vs. pemetrexed 2.9 months) were found among the three groups. Female gender was related to a good response to EGFR TKIs (p=0.047). Skin rash in the erlotinib group (p=0.037) and adenocarcinoma in the pemetrexed group (p=0.02) were related to improved progression-free survival. Few side effects were reported. CONCLUSIONS: Both EGFR TKIs and pemetrexed therapy for non-squamous non-small-cell lung cancer were efficient and tolerable after the failure of first-line platinum-based chemotherapy. Further prospective studies are needed to validate the predictive role of the suggested clinical parameters in this study.
Adenocarcinoma ; Disease-Free Survival ; Exanthema ; Female ; Follow-Up Studies ; Glutamates ; Guanine ; Humans ; Lung ; Lung Neoplasms ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Erlotinib Hydrochloride ; Pemetrexed

BACKGROUND: The purpose of this study was to promote organ donation by active identification and proper management of brain-dead donor with collaborating network system and to assume operating expenses in the setting of independent organ procurement organization (IOPO) in Korea. METHODS: Seoul National University Hospital and Gachon University Gill Hospital worked together as regional OPO during 8 months from April to December 2008. RESULTS: We constructed cooperative network system with five base-hospitals by MOU (memorandum of understanding). We visited 138 hospitals 223 times and built up brain-dead organ donation. Among total 265 dead patients in intensive care unit (ICU), 95 (36%) patients were considered as potential organ donors, but only 14 (14.7%) donated their organs actually. During the previous 8 months, there were 67 contacts for potential donor evaluation and total 100 solid organs were actually procured from 31 brain-dead donors except 4 cases. We also established and applied a flow chart and critical pathway of potential brain-dead donor. It was worthy of notice to manage 3 brain-dead donors and successfully procured their organs without donor transportation to HOPO. Apart from operating and depreciation expenses, we could estimate the expenses loss of mean 850,000 won per organ in the current system. CONCLUSIONS: Our results showed hope for success of IOPO in Korea which would be founded in the near future. Besides persistent active relationship with regional hospitals, a certain degree of financial support or other means such as increase of organ fee and medical insurance coverage should be considered.
Animals ; Brain ; Brain Death ; Critical Pathways ; Depreciation ; Fees and Charges ; Financial Support ; Gills ; Humans ; Insurance Coverage ; Intensive Care Units ; Korea ; Tissue and Organ Procurement ; Tissue Donors ; Transportation

BACKGROUND: This study was to evaluate a nationwide nosocomial infection rate and antimicrobial resistance in intensive care units(ICUs) in Korea. METHODS: The study was carried out at 16 university-affiliated teaching hospitals from July through October 2004. We performed a prospective multicenter study to investigate nosocomial infection rates, device-associated infection rated, and causative pathogens and their antimicrobial resistance. RESULTS: The urinary tract was the most commonly involved site. Nosocomial infection rate was 12.48 in medical. ICU (MICU), 9.59 in medical surgical ICU (MSICU), 14.76 in surgical ICU (MSICU), and 11.60 in other lCU. Device-associated infection rates were as follow: 1) rates of urinary catheter-associated urinary tract infection were 4.26 in MICU, 3.17 in SICU, 4.88 in MSICU, and 5.87 in other ICU; 2) rates of central line-associated bloodstream infection were 3.24 in MICU, 1.56 in SlCU, 2.36 in MSICU, and 1.78 in other ICU; 3) rates of ventilator-associated pneumonia were 3.61 in MlCU, 13.05 in SICU, 1.68 in MSICU, and 4.84 in other lCU. Staphylococcus aureus was the most frequently identified microorganism in this study; 93% of S. aurues were resistant to methicillin; 17% of Pseudomonas aeruginosa isolated were resistant to imipenem; 11% of Enterococcus faecium and 18% of Enterococcus faecalis showed resistance to vancomycin. Over a half of Acinetobacter spp, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Escherichia coli showed resistant to fluoroquinolone. Conclusion: This study shows the seriousness of antimicrobial resistance and the importance of infection control in the lCU in Korea. This study should provide a theoretical strategy to enforce the infection control.
Acinetobacter ; Cross Infection* ; Enterococcus faecalis ; Enterococcus faecium ; Escherichia coli ; Hospitals, Teaching ; Hospitals, University* ; Imipenem ; Infection Control ; Intensive Care Units* ; Critical Care* ; Klebsiella pneumoniae ; Korea* ; Methicillin ; Pneumonia, Ventilator-Associated ; Prospective Studies ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Stenotrophomonas maltophilia ; Urinary Tract ; Urinary Tract Infections ; Vancomycin

BACKGROUND AND OBJECTIVES: In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model. MATERIALS AND METHODS: An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later. RESULTS: The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups. CONCLUSION: Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.
Administration, Oral ; Animals ; Arteries ; Coronary Disease ; Coronary Restenosis ; Coronary Vessels ; Hyperplasia ; Myocytes, Smooth Muscle ; Phenobarbital ; Rats ; Stents ; Thrombin*