Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Purpose: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a major public health problem of international concern. It is important to estimate its impact of COVID-19 for health policy decision-making. We estimated the years of life lost (YLLs) due to COVID-19 in high-incidence countries. Methods: We collected the YLLs due to COVID-19 in 30 high-incidence countries as of April 13, 2020 and followed up as of July 14, 2020. Incidence and mortality were collected using each country's formal reports, articles, and other electronic sources. The life expectancy of Japanese females by age and the UN population data were used to calculate YLLs in total and per 100,000. Results: As of April 22, 2020, there were 1,699,574 YLLs due to COVID-19 in 30 high-incidence countries. On July 14, 2020, this increased to 4,072,325. Both on April 22 and July 14, the total YLLs due to COVID-19 was highest in the USA (April 22, 534,481 YLLs; July 14, 1,199,510 YLLs), and the YLLs per 100,000 population was highest in Belgium (April 22, 868.12 YLLs/100,000;July 14, 1,593.72 YLLs/100,000). YLLs due to COVID-19 were higher among males than among females and higher in those aged ≥ 60 years than in younger individuals. Belgium had the highest proportion of YLLs attributable to COVID-19 as a proportion of the total YLLs and the highest disability-adjusted life years per 100,000 population. Conclusion This study estimated YLLs due to COVID-19 in 30 countries. COVID-19 is a high burden in the USA and Belgium, among males and the elderly. The YLLs are very closely related with the incidence as well as the mortality. This highlights the importance of the early detection of incident case that minimizes severe acute respiratory syndrome coronavirus-2 fatality.

BACKGROUND: Disease burden can be represented by health-related parameters such as disability-adjusted life years and economic burden. Economic burden is an important index, as it estimates the maximum possible cost reduction if a disease is prevented. This study aimed to determine the economic burden of 238 diseases and 22 injuries in Korea in 2015. METHODS: Economic burden was estimated with a human resources approach from a social perspective, and direct and indirect costs were calculated from insurance claims data and a cause of death database. Direct costs were divided into medical costs (including hospital admission, outpatient visit, and medication use) and nonmedical costs (including transportation and caregiver costs). Indirect costs from lost productivity, either from the use of healthcare service or premature death, were analyzed. RESULTS: In 2015, the estimated economic burden was USD 133.7 billion (direct: USD 65.5 billion, indirect: USD 68.2 billion). The total cost of communicable diseases was USD 16.0 billion (11.9%); non-communicable diseases, USD 92.3 billion (69.1%); and injuries, USD 25.4 billion (19.0%). Self-harm had the highest costs (USD 8.3 billion), followed by low back pain (LBP, USD 6.6 billion). For men, self-harm had the highest cost (USD 7.1 billion), while LBP was the leading cost (USD 3.7 billion) for women. CONCLUSION A high percentage of Korea's total socioeconomic disease burden is due to chronic diseases; however, unnoticed conditions such as infectious diseases, injuries, and LBP are high in certain age groups and differ by gender, emphasizing the need for targeted social interventions to manage and prevent disease risk factors.

PURPOSE: Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases. MATERIALS AND METHODS: We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships. RESULTS: A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs. CONCLUSION: The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.
Aged ; Aging ; Clinical Decision-Making ; Complement System Proteins ; Data Mining ; Decision Trees ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Learning* ; Prescriptions

OBJECTIVE: Sinapic acid (SA, Sinapine), small naturally occurring hydroxycinnamic acid, has a GABA(A) receptor agonistic property and free radical scavenging activity. We examined potential neuroprotective effects of sinapic acid (SA) using global cerebral ischemia animal model. METHODS: MTT assay was performed to determine cytotoxic effects of SA. To examine the neuroprotective effects of SA, SA was administrated for 14 d before 4-vessel occlusion. Also, to determine whether SA prevents cognitive impairment, Morris water maze was performed. RESULTS: In this study, the efficacy of SA for the prevention of neuronal damage and for the reduction of memory impairment was investigated. CONCLUSION: The results indicate that SA confers significant neuroprotection especially for ischemic hippocampal neurons.
Animals ; Brain Ischemia ; Coumaric Acids ; Glycosaminoglycans ; Hippocampus ; Ischemia ; Maze Learning ; Memory ; Neurons ; Neuroprotective Agents ; Rats ; Receptors, GABA-A

IL-17A is a pro-inflammatroy cytokine secreted by activated T cells. The IL-17 family consist of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. IL-17A and IL-17F are produced primarily in activated T cells. In contrast, IL-17B, IL-17C, IL-17D and IL-17E are expressed in a wide assortment of tissues. Their functions partially overlap those of IL-17A, although they have not been as thoroughly investigated. The receptor for IL-17A (IL-17R) is widely expressed in a variety of tissues. IL-17A and IL-17E mRNAs were expressed in only EL4 cells. IL-17C mRNA expression was observed in the thymic subcapsular/cortex epithelial cells (SNEC), cortex or cortical reticular cells (CREC), medullary epithelial cells (MEC), medullary interdigitating-like cells (MDC), thymocytes and EL4 cells. However, IL-17C mRNA was not expressed in RAW 264.7 cells. Immunohistochemical study also demonstrated not only the presence of IL-17A mainly in the thymic epithelial cells, but also the upregulated expression of IL-17A in the thymic epithelial cells of the regenerating thymus. Thus, the results of the present study suggest that IL-17A expressed in the thymocytes and thymic epithelial cells could play an important role in the development of new T cells to replace T cells damaged by cyclophosphamide treatment during thymus regeneration.
Animals ; Cyclophosphamide ; Epithelial Cells ; Humans ; Interleukin-17 ; Rats ; Regeneration ; RNA, Messenger ; T-Lymphocytes ; Thymocytes ; Thymus Gland

PURPOSE: The purpose of this study was to provide data for development of the Journal of Fundamentals of Nursing through reviewing classification of sectional editorship. METHODS: Descriptive statistical analysis was used, to identify content then, the classifications of sectional editorship were reviewed. RESULTS: The categories, "Basic concepts of nursing" (30.2%:17.9%), "Needs for comfort" (15.9%:13.1%), "Nursing education" (12.7%:12.7%), and "Needs for activity and exercise" (7.1%:7.1%) were most frequent through both the 1st and 2nd sectional editorship. CONCLUSION: Classification of sectional editorship was developed to clarify the educational purpose of fundamentals of nursing, and was modified through reflections by researchers. The current classification of sectional editorship is not a permanent formula, so using various viewpoints in further examination is needed.
Nursing Research

PURPOSE: Recently the incidence of severe hyponatremia is increasing in old patients but there is no report about clinical findings of old patients with hyponatremia. We evaluated the cause and clinical manifestations of severe hyponatremia in old patients who had been admitted via emergency room. METHODS: We retrospectively reviewed clinical records of the hyponatremic patients who had been admitted from 2000 to 2007. We enrolled 53 patients (Age >60 years, Na <125 mEq/L) without severe liver cirrhosis, heart failure or chronic kidney disease. We analyzed data to evaluate the differences of clinical manifestations according to the presence of symptoms, taking diuretics, urine sodium concentrations and the degree of hyponatremia. RESULTS: Mean serum sodium concentration was 111.4+/-6.9 mEq/L and urine sodium concentration was 68.7+/-43.8 mEq/L. There was no difference in serum sodium concentration according to age. Twenty-nine (54.7%) patients had nausea and vomiting and 19 patients (35.8%) had neurologic symptoms. Patients with neurologic symptoms showed lower serum and urine sodium concentration than patients without neurologic symptoms. The main causes of severe hyponatremia were poor oral intake (79.2%), diuretics use (37.7%) and recent operation (15.1%). The mean sodium concentration of the fluid administered to achieve 125 mEq/L of serum sodium level was 336.5+/-160.6 mEq/L. CONCLUSION: The urinary sodium loss, e.g., diuretics abuse, may be the main cause of severe hyponatremia in elderly patients over 60 years. In elderly patients, diuretics should be carefully administered with frequent electrolyte monitoring.
Aged ; Diuretics ; Emergencies ; Heart Failure ; Humans ; Hyponatremia ; Incidence ; Liver Cirrhosis ; Nausea ; Neurologic Manifestations ; Renal Insufficiency, Chronic ; Retrospective Studies ; Sodium ; Vomiting

The JNK inhibitor SP600125 strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. We investigated the effects of SP600125 on the inhibition of cell proliferation and the cell cycle, and on microtubule dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 results in significant G2/M cell cycle arrest with elevated p21 levels, phosphorylation of histone H3 within 24 h, and endoreduplication with elevated Cdk2 protein levels after 48 h. SP600125 also induces significant abnormal microtubule dynamics in vivo. High concentrations of SP600125 (200 microMeter) were required to disorganize microtubule polymerization in vitro. Additionally, SP600125-induced delayed apoptosis and cell death was accompanied by significant poly ADP-ribose polymerase (PARP) cleavage and caspase-3 activity in the late phase (at 72 h). Endoreduplication showed a greater increase in ectopic Bcl-2-expressing U937 cells at 72 h than in wild-type U937 cells without delayed apoptosis. These results indicate that Bcl-2 suppresses apoptosis and SP600125-induced G2/M arrest and endoreduplication. Therefore, we suggest that SP600125 induces mitotic arrest by inducing abnormal spindle microtubule dynamics.
Anthracenes/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Apoptosis/*drug effects ; Cell Cycle/drug effects ; Enzyme Inhibitors/therapeutic use ; Humans ; JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors/*metabolism ; Leukemia/drug therapy ; Tubulin/*metabolism