Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

The time between symptom onset and arrival at an emergency department (ED) (S2D) is a crucial time for optimal intravenous reperfusion care for ischemic stroke. We aimed to analyze the effect of emergency medical services (EMS) utilization and inter-hospital transfer on S2D in Korea. Ischemic stroke patients were prospectively enrolled from November 2007 to December 2012 in 23 tertiary and teaching hospital EDs in Korea. Of 31,443 adult ischemic stroke patients, 20,780 were categorized into 4 groups based on modes of EMS utilization and inter-hospital transfer: direct transport to destination ED by EMS (EMS direct; n=6,257, 30.1%), transfer after transport to another ED by EMS (EMS indirect; n=754, 3.6%), direct transport to the ED without using EMS (non-EMS direct; n=8,928, 43.0%), and transfer after visiting another hospital without using EMS (non-EMS indirect; n=4,841, 23.3%). Our primary outcome variable was of S2D within 2 hr (S2D < or =2 hr) and found that 30.8% of all patients and 52.3%, 16.4%, 25.9%, and 13.9% of EMS direct, EMS indirect, non-EMS direct, and non-EMS indirect, respectively, achieved S2D < or =2 hr. Adjusted odds ratio for S2D < or =2 hr were 6.56 (95% confidence interval [CI], 5.94-7.24), 2.27 (95% CI, 2.06-2.50), and 1.07 (95% CI, 0.87-1.33) for EMS direct, non-EMS direct, and EMS indirect, respectively. Patients directly transported to destination hospitals by the EMS show the highest proportion of therapeutic time window for optimal care in ischemic stroke.
Aged ; Emergency Medical Services/*statistics & numerical data ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Republic of Korea ; Stroke/*diagnosis ; Tertiary Care Centers ; Time Factors

BACKGROUND/AIMS: DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. METHODS: Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. RESULTS: The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. CONCLUSIONS: DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.
Animals ; Blotting, Western ; Dextrans ; Fluorescein ; Indomethacin ; Inflammation ; Intestine, Small ; MAP Kinase Signaling System ; Permeability* ; Phosphotransferases ; Rats

PURPOSE: Inter-hospital transport poses a number of challenging issues, including prolonging the time interval from symptoms to optimal reperfusion therapy after ischemic stroke. It is unclear whether urbanization is associated with outcomes of inter-hospital transfer including length of stay at the referring hospital (D1LOS). METHODS: A prospective stroke registry from 23 Emergency Departments (ED) from 2007 to 2012 over the nation was collected. Ischemic stroke patients who arrived at the first ED within 24 hours of onset (S2D1) were enrolled. Patients were excluded if time intervals or address were incorrect or missing. Main exposure was urbanization level; urban > or =10,000 and rural <10,000 population. Primary outcome was D1LOS. The secondary outcomes were symptoms to door of the first ED (S2D1) and transfer time to the final ED (T2D2). We compared the D1LOS, S2D1, and T2D2 with median and inter-quartile range (IQR) by urbanization level. RESULTS: Of 5,909 patients transferred from other hospitals, 2,289 patients were analyzed; 1,441 (63%) patients in urban areas, 848 (37%) patients in rural areas were included. The D1LOS and S2D1 in urban was longer than those in rural; 100 minutes (IQR 50~208) for urban VS 82.5 minutes (IQR 48~170.5) for rural (p=0.01) and 66 minutes (IQR 30~240) for urban VS 90 minutes (IQR 30~330) for rural (p=0.001). T2D2 in urban was shorter than that in rural; 54 minutes (IQR 36~78), 40 minutes (IQR 25~65) (p< or =0.00), respectively. CONCLUSION: Urban EDs showed longer D1LOS before transferring patients to the hospital for definite care. Strategy for reducing delay due to inter-hospital transport should differ according to urbanization.
Emergency Medical Services ; Emergency Service, Hospital ; Humans ; Length of Stay ; Patient Transfer ; Reperfusion ; Stroke* ; Urbanization*

PURPOSE: Emergency physicians are usually more experienced in emergency situations; therefore, a cardiopulmonary resuscitation team with an emergency physician as a leader would be operated effectively. The aim of this study is to evaluate the effectiveness of a cardiopulmonary resuscitation that includes an emergency physician. METHODS: A retrospective analysis for in-hospital arrests that occurred in the general ward was conducted based on the in-hospital cardiopulmonary resuscitation registry of a tertiary care university hospital in Korea from January 1, 2005 through December 31, 2010. We compared outcomes of cardiopulmonary resuscitation performed by a team that included an emergency physician with those by a cardiopulmonary resuscitation team that included a non-emergency physician. RESULTS: Survival rates at discharge were 29.6% for the emergency physician team and 17.7% for the non-emergency physician team. The good neurologic outcome rates at discharge were 20.6% and 10.6%, respectively. In multivariate analysis with adjustment for pre-arrest patient condition and arrest variables, survival rate did not differ significantly between the two groups. However, the good neurologic outcomes showed an association with the emergency physician team. CONCLUSION: For in-hospital cardiac arrest, outcomes for patients who were rescued by the emergency physician-directing CPR team might be comparable or better, compared with those by the non-emergency physician team.
Cardiopulmonary Resuscitation ; Emergencies ; Heart Arrest ; Humans ; Korea ; Multivariate Analysis ; Patients' Rooms ; Retrospective Studies ; Survival Rate ; Tertiary Healthcare

PURPOSE: Anaplastic thyroid cancer is known to have a poor prognosis due to its aggressive and rapid metastasis with median survival of less than 6 months. Multimodal treatment involving surgery and chemoradiotherapy has been used to improve the survival of patients. Here, we retrospectively review of treatment outcome of 13 consecutive patients who were treated at a single center. MATERIALS AND METHODS: We retrospectively reviewed medical records of 13 anaplastic thyroid cancer patients who received multidisciplinary treatment between 2006 and 2010. Kaplan-Meier survival curve was used to analyze progression-free survival and overall survival of patients. RESULTS: The median patient age at diagnosis was 69 years, and six patients had stage IVc diseases. Eight patients received primary surgery followed by radiotherapy or concurrent chemoradiotherapy (CCRT). Five patients received weekly doxorubicin-based definitive CCRT, but only one patient's condition remained stable, while the rest experienced rapid disease progression. The median progression-free survival was 2.8 months (95% CI, 1.2-4.4 months), and the median overall survival was 3.8 months (95% CI, 3.0-4.6 months). CONCLUSION: Patients with anaplastic thyroid cancer showed poor prognosis despite multimodality treatment. Therefore, identification of novel therapeutic targets is warranted to take an effective mode of treatment.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Doxorubicin/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thyroid Neoplasms/*drug therapy/mortality ; Treatment Outcome

BACKGROUND: Midazolam has a direct relaxing effect on vascular smooth muscle, but the mechanisms that this agent produces muscle relaxation are not fully understood. The current study was performed to identify the effects of the midazolam on K+ channels current in rabbit cerebral arterial smooth muscle cells. METHODS: Whole cell patch-clamp recording technique was used to evaluate the effects of midazolam (0.1 to 100micrometer) on outward K+ channel currents in dispersed rabbit cerebral arterial smooth muscle cells. RESULTS: Outward K+ currents of rabbit cerebral artery smooth muscle cells were voltage-dependent. Midazolam (10, 100micrometer) tested significantly inhibited outward K+ currents in a dose-dependent manner and half-blocking concentration (IC50) was 15.94micrometer at 60 mV. CONCLUSIONS: Midazolam inhibit outward K+ currents of rabbit cerebral arterial smooth muscle cells. Further study will be needed to determine the effect of midazolam on calcium channel current because it is unclear if the inhibitory effect of midazolam on outward K+current induces vasoconstriction.
Calcium Channels ; Cerebral Arteries ; Midazolam* ; Muscle Relaxation ; Muscle, Smooth* ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle* ; Vasoconstriction

This study was conducted to investigate dietary and other factors affecting bone mineral density (BMD) in Korean premenopausal women. Seventy-eight premenopausal women who visited the Health Promotion Center for health examinations volunteered to participate in this study. They were divided into two groups according to their bone status as shown by their T-scores: a non-osteoporotic group and a osteoporotic group. The results are as follows: The mean BMDs of the lumbar spine and femoral neck were 1.21 +/- 0.02 g/cm2 and 0.97 +/- 0.04 g/cm2, respectively. The BMD levels of the osteoporotic group were significantly lower than those of the non-osteoporotic group (p < 0.001, respectively). The heights of the women in the osteoporotic group were significantly lower than those of the non-osteoporotic group (p < 0.01) however, their body weights did not show any significant differences although they tended to be lower. The mean daily intake of energy was 1720 +/- 52 kcal. When the nutrient intake was compared with the Korean recommended dietary allowances (RDA), calcium, Fe, vitamin A and riboflavin intakes were lower than the RDA. Their was no significant difference in the nutrient intake of the non-osteoporotic group and osteoporotic group except for the intakes of protein, fat and niacin. Their was no significant difference between the non-osteoporotic group and the osteoporotic group and all were within the normal range. However, the serum alkaline phosphatase level of the osteoporotic group was significantly higher than that of the non-osteoporotic group (p < 0.001). Height measurements showed positive correlations with lumbar spine bone mineral density (LBMD, r = 0.332, p < 0.01) however there was no correlation with femoral neck bone mineral density (NBMD). Age, age at menarche, body weight, body mass index (BMI) and obesity showed no correlation with BMD. The BMD of the lumbar spine was significantly and positively related to the intake of niacin and vitamin C (r = 0.236, p < 0.05; r = 0.274, p < 0.05). Serum levels of calcium and phosphorus showed negative correlations with LBMD (r = -0.698, p = 0.0001; r = -0.503, p = 0.0001, respectively). The results suggested that the BMD of the lumbar spine was positively related to the intake of niacin and vitamin C in premenopausal women. Therefore, this study confirmed that one of the most effective ways to minimize bone loss would be have a higher intake of niacin and vitamin C rich foods and engaging habitually in physical activity may have a beneficial effect on BMD in the premenopausal period.
Alkaline Phosphatase ; Ascorbic Acid ; Body Mass Index ; Body Weight ; Bone Density ; Calcium ; Female ; Femur Neck ; Health Promotion ; Humans ; Menarche ; Motor Activity ; Niacin ; Obesity ; Phosphorus ; Premenopause ; Recommended Dietary Allowances ; Reference Values ; Riboflavin ; Spine ; Vitamin A

PURPOSE: This study was performed to investigate the clinical features of large cell neuroendocrine carcinomas (LCNEC). MATERIALS AND METHODS: We retrospectively reviewed the histopathology and clinical information of 37 patients with LCNEC, diagnosed between June 1992 and May 2002 at the Severance Hospital, and performed immunohistochemical (IHC) staining. RESULTS: The prevalence of LCNEC among primary lung cancers was 0.3%, 37 out of 13, 012 cases over a 10 year period. The mean age was 61+/-12 years old, with 34 (92%) males and 3 (8%) females. 30 patients smoked, with an average of 42 packs per year. A cough was the most frequent symptom. The tumor was located at the periphery of the lung in 24 cases (65%). Among the 30 cases that underwent surgery, 4 were diagnosed pathological stage IA, 11 IB, 1 IIB, 13 IIIA and 1 IIIB. The 7 clinically non-operable cases were IIIB in 3, and IV in 4. The positive rates of CD56, thyroid transcription factor-1 (TTF-1), chromogranin A, synaptophysin and 34betaE12 for tumor cells were 88.9, 55.6, 42.1, 31.6 and 21.1%, respectively, from the IHC staining. The median survival time and 5 year-survival rate were 24 months and 27%, respectively. The group that underwent surgery had a better prognosis than those that did not. CONCLUSION: The positive rates for the tumor markers varied, but those of the CD56 and TFT-1 were the highest. The possibility of LCNEC needs to be evaluated for the following situations: small cell carcinomas located at the periphery and not responding chemotherapy, small cell carcinomas diagnosed by percutaneous needle aspiration, poorly differentiated non-mall cell carcinomas, with uncertain histologic type, and unclassified neuroendocrine tumor, etc.
Carcinoma, Neuroendocrine* ; Carcinoma, Small Cell ; Chromogranin A ; Cough ; Drug Therapy ; Female ; Humans ; Lung ; Lung Neoplasms ; Male ; Needles ; Neuroendocrine Tumors ; Prevalence ; Prognosis ; Retrospective Studies ; Smoke ; Synaptophysin ; Thyroid Gland ; Biomarkers, Tumor

Osteoporosis, the typical metabolic bone disease of the elderly, is characterized by a reduction in bone mineral density (BMD) and increased fracture risk. Genetic and environmental factors are known to play a key role in bone metabolism, and diet is also considered to be one of the important factors. The purpose of the present study was to investigate the relationship among the factors affecting BMD, including stature, body weight, age, time period since onset of menopause, and biochemical markers of bone turnover in postmenopausal women. Seventy-eight postmenopausal women who visited health promotion center for health examinations volunteered to participate in this study and they were divided into two groups according to the time period since onset of menopause : women with a time period since onset of menopause of less than 5 years (Group 1) and women with a time period since onset of menopause of 5 years or more (Group 2). The demographic characteristics and dietary intake were surveyed using a questionnaire. BMDs of the lumbar spine and femoral neck of subjects were measured by dual energy X-ray absorptiometry. Serum levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH), known to be indicators of bone related hormone status, were anlyzed. Serum samples were measured for calcium, phosphorus, alkaline phosphatase, and osteocalcin as bone formation indicators, and urine was analysed for deoxypyridinoline, creatinine, calcium, and sodium as bone resorption indicators. The results are as follow : The mean BMDs of the lumbar spin and femoral neck were 1.02+/-0.02 g/cm2 and 0.81 +/-0.02 g/cm2, respectively, and the BMD level of Group 2 was significantly lower than tat of Group 1 (p<0.01, p<0.05, respectively). The mean daily intake of energy was 1838 +/- 55 kcal. When nutrient intake was compared with the recommended dietary allowances (RDA) of the subjects, only calcium, vitamin A and riboflavin intake showed means lower than the RDA. The nutrient intake did not show any significant differences between Group 1 and 2 Serum and urine levels of biochemical markers of bone turnover did not show any significant differences between Group 1 and 2, and all were within the normal range. However, the PTH and deoxypyridinoline levels showed a tendency to be higher, and the osteocalcin level to be lower in Group 2 than in Group 1. Although age and years after menopause (YAM) showed negative correlations with lumbar spine bone mineral density (LBMD) (r= -0.38, p<0.001, and r= -0.26, p<0.05, respectively), no correlation was found with femoral neck bone mineral density (NBMD). While height, body weight and body mass index (BMI) showed a positive correlation with LBMD (r= 0.32, p<0.001, r= 0.38, p<0.001, r= 0.22, p= 0.05, respectively), only body weight and BMI showed a positive correlation with NBMD (r= 0.30, p<0.01, and r= 0.27, p<0.05, respectivley). There was no significant corealtion between BMDs and the nutrient intake of subjects, except in the case of carbohydrates (r= 0.22, p<0.05). Also, serum and urine levels of bone turnover markers showed no significant correlation with nutrient intake. On the other hand, serum osteocalcin had a positive correlation with vitamin C intake (r= 0.22, p= 0.05), and urine deoxypyridinolin showed a negative correlation with niacin intake (r= -0.22, p= 0.05). Urinary na was negatively correlated with protein intake(r= -0.23, p= 0.05). The results suggested that it is difficult to prevent the decrease in bone mass among postmenopausal women eating the usual Korean diet. However, the BMDs of the lumbar spine and femoral neck were positively related to body weight ad BMI in postmenopausal women. Therefore, this study confirmed that one of the most effective ways to minimize bone loss in postmenopausal women would be to maintain an adequate body weight with balanced nutrient intake and activity in the pre-and postmenopausal periods.
Absorptiometry, Photon ; Aged ; Alkaline Phosphatase ; Ascorbic Acid ; Biomarkers ; Body Height ; Body Mass Index ; Body Weight ; Bone Density ; Bone Diseases, Metabolic ; Bone Resorption ; Calcium ; Carbohydrates ; Creatinine ; Diet ; Female ; Femur Neck ; Hand ; Health Promotion ; Humans ; Menopause ; Metabolism ; Niacin ; Osteocalcin ; Osteogenesis ; Osteoporosis ; Parathyroid Hormone ; Phosphorus ; Postmenopause ; Recommended Dietary Allowances ; Reference Values ; Riboflavin ; Sodium ; Spine ; Vitamin A ; Surveys and Questionnaires