SCI 발표논문
2015년 276편
- 1562015
제1저자 정영호, 이도영 · 교신저자 김덕겸
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Clinical significance of laryngopharyngeal reflux in patients with chronic obstructive pulmonary disease.Int J Chron Obstruct Pulmon Dis. 2015;10:1343-51.
PubMed IF 4.1 호흡기내과Abstract
BACKGROUND Although chronic obstructive pulmonary disease (COPD) is closely associated with gastroesophageal reflux disease (GERD), the clinical significance of laryngopharyngeal reflux (LPR) is not fully understood in COPD.
METHODS Prospective cohorts were established among 118 patients with COPD from March 2013 to July 2014. Thirty-two age-matched and sex-matched normal controls, who had routine health check-ups during the study period, were included. Laryngopharyngeal reflux finding scores (RFS) and reflux symptom index (RSI) for LPR were subjected to association analysis with severity and acute exacerbation of COPD during the 1-year follow-up.
RESULTS The mean age of patients enrolled in the study was 69.2±8.8 years, with 93.2% being male. Positive RFS (>7) and RSI (>13) were observed in 51 (42.5%) and six patients (5.0%), respectively. RFS and RSI were significantly higher in patients with COPD than in normal, healthy patients (P<0.001). RFS was significantly correlated with residual volume/total lung capacity (%, P=0.048). Scores for diffuse laryngeal edema, erythema, and hyperemia were significantly higher in the high-risk group (Global Initiative for Chronic Obstructive Lung Disease classification C and D; P=0.025 and P=0.049, respectively), while RSI was significantly higher in the more symptomatic group (Global Initiative for Chronic Obstructive Lung Disease classification B and D; P=0.047). RSI and RFS were significant predictors for severe acute exacerbation of COPD (P=0.03 and P=0.047, respectively), while only RSI was associated with severity of dyspnea.
CONCLUSION Laryngeal examination and evaluation of laryngeal reflux symptom could be a surrogate clinical indicator related to severe acute exacerbation of COPD. Further studies of LPR in COPD patients should be considered.
- 1552015
제1저자 이대원 · 교신저자 한세원/강경훈
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Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX.Clin Epigenetics. 2015;7(1):63.
PubMed IF 5.7 혈액종양내과Abstract
BACKGROUND Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence of methylation status has not been clearly defined. We have investigated the prognostic role of promoter methylation using eight CpG island methylator phenotype (CIMP) markers in 497 stage II or III CRC patients who underwent curative resection followed by adjuvant FOLFOX. Overall survival (OS) and disease-free survival (DFS) were compared between subgroups classified by methylation status, and interactions with clinico-pathological features were analyzed.
RESULTS CIMP-high (≥5 methylated loci) and concurrent methylation in NEUROG1 and CDKN2A (p16) were found in 5.8 and 7.9 % of patients, respectively. Although CIMP-high status was not associated with survival, concurrent methylation in NEUROG1 and CDKN2A (p16) was associated with shorter OS and DFS. Moreover, the prognostic role of the concurrent methylation was different among sex. The negative prognostic impact was only observed in male but not in female (interaction p value = 0.026 for OS and 0.011 for DFS). In male, the 5-year OS was 61.6 % in concurrent methylation (+) and 91.7 % in concurrent methylation (-) (p < 0.001) whereas it was 95.0 and 92.8 % in female, respectively (p = 0.78).
CONCLUSIONS Concurrent methylation in NEUROG1 and CDKN2A is associated with poor survival in CRC treated with adjuvant FOLFOX. Interaction analysis indicates that the prognostic role is different according to sex.
- 1542015
제1저자 김경민 · 교신저자 임수
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Anti-diabetic efficacy of KICG1338, a novel glycogen synthase kinase-3β inhibitor, and its molecular characterization in animal models of type 2 diabetes and insulin resistance.Mol Cell Endocrinol. 2015;409:1-10.
PubMed IF 3.4 내분비대사내과Abstract
Selective inhibition of glycogen synthase kinase-3 (GSK3) has been targeted as a novel therapeutic strategy for diabetes mellitus. We investigated the anti-diabetic efficacy and molecular mechanisms of KICG1338 (2-(4-fluoro-phenyl)-3H-imidazo[4,5-b]pyridine-7-carboxylic acid(4-methyl-pyridin-3-yl)-amide), a GSK3β inhibitor, in three animal models: Otsuka Long-Evans Tokushima Fatty (OLETF) rats, leptin receptors-deficient db/db mice, and diet-induced obese (DIO) mice. Biochemical parameters including glucose tolerance tests and gene expressions associated with glucose metabolism were investigated. Glucose excursion decreased significantly by KICG1338-treated OLETF rats, accompanied by increase in insulin receptor substrate-1 and glucose transporter (GLUT)-4 expressions in muscle and decreased GLUT-2 expression in liver. Glucose-lowering effects were similarly observed in KICG1338-treated db/db and DIO mice. KICG1338 treatment increased adiponectin levels and decreased TNF-α levels. KICG1338 therapy also led to greater β-cell preservation and less hepatic fat infiltration with decreased expressions of genes involved in inflammation and endoplasmic reticulum stress. These data demonstrate anti-diabetic efficacy of KICG1338, a novel GSK3β inhibitor.
- 1532015
제1저자 김령효 · 교신저자 김윤준
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Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population.Infect Genet Evol. 2015;33:72-6.
PubMed IF 2.8 소화기내과Abstract
A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC.
- 1522015
제1저자 김범석 · 교신저자 허대석
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Neutrophil to lymphocyte ratio improves prognostic prediction of International Prognostic Index for patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.Leuk Lymphoma. 2015;56(7):2032-8.
PubMed IF 2.1 혈액종양내과Abstract
The purpose of this study was to analyze the pre- and post-treatment neutrophil to lymphocyte ratio (pre- and post-NLR) in combination with immunologic profiles in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). A total of 447 newly diagnosed patients with DLBCL treated with R-CHOP were analyzed retrospectively. A pre-NLR ≥ 3 was independently associated with poor progression-free survival (PFS) (hazard ratio [HR] = 2.19, p < 0.001) and overall survival (OS) (HR = 2.89, p < 0.001). In patients with high pre-NLR, reduction of the post-NLR to < 3 after R-CHOP was correlated with improved survival. Low pre-NLR (< 3) was also associated with a higher number of peripheral CD19 + lymphocytes (p = 0.049) and NK cells (p = 0.031). In conclusion, a pre-NLR ≥ 3 was an independent prognostic factor for PFS and OS in patients with DLBCL treated with R-CHOP.
- 1512015
제1저자 문재훈 · 교신저자 김기웅, 장학철
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Serum 25-hydroxyvitamin D level and the risk of mild cognitive impairment and dementia: the Korean Longitudinal Study on Health and Aging (KLoSHA).Clin Endocrinol (Oxf). 2015;83(1):36-42.
PubMed IF 2.8 내분비대사내과Abstract
OBJECTIVE The association of low vitamin D status with mild cognitive impairment (MCI), a preclinical condition that can lead to dementia, has not yet been fully explored. Our aim was to investigate the association between vitamin D status and the future risk of MCI and dementia in older adults.
DESIGN, SETTING AND PARTICIPANTS We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Four hundred and twelve elderly participants who completed evaluations of cognitive function and metabolic parameters in 2005-2006 and 2010-2011 were analysed.
MAJOR OUTCOME MEASURE The rate of development of MCI or dementia during the study period was compared according to baseline vitamin D status. Binary logistic regression analysis was performed to investigate any independent association between vitamin D status and the risks of MCI or dementia.
RESULTS Among 405 subjects that remained after excluding seven demented subjects at baseline, 338 subjects remained unchanged or improved in their diagnosis for cognitive function during the study period, whereas 67 subjects showed progression to MCI or dementia. When analyzing 236 subjects whose baseline mini-mental state examination (MMSE) scores were <27, severe vitamin D deficiency at baseline, defined as <25 nmol/l, was independently associated with the progression of cognitive impairment. Among 297 subjects who were normal at baseline, 50 acquired MCI and 247 remained normal. Severe vitamin D deficiency was also independently associated with the development of MCI when analyzing 145 subjects whose baseline MMSE scores were <27.
CONCLUSION Severe vitamin D deficiency was independently associated with the future risk of MCI as well as dementia, especially in older adults whose baseline MMSE scores had decreased only modestly.
- 1502015
제1저자 이성태 · 교신저자 이동호
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Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and 14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for Helicobacter pylori Infection.Gut Liver. 2015;9(4):478-85.
PubMed IF 4.1 소화기내과Abstract
BACKGROUND/AIMS Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen.
METHODS From August 2004 to October 2012, a total of 949 patients (mean age, 54.32±12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the (13)C-urea breath test, rapid urease test or histology.
RESULTS The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively).
CONCLUSIONS The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.
- 1492015
제1저자 홍아람 · 교신저자 임수
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Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial.Diabetes Res Clin Pract. 2015;109(1):141-8.
PubMed IF 4.6 내분비대사내과Abstract
The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (P<0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137).
- 1482015
제1저자 최윤진 · 교신저자 김나영
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Influence of TGFB1 C-509T polymorphism on gastric cancer risk associated with TGF-β1 expression in the gastric mucosa.Gastric Cancer. 2015;18(3):526-37.
PubMed IF 6.1 소화기내과Abstract
BACKGROUND Transforming growth factor-β1 (TGF-β1) has dual roles inhibiting and promoting carcinogenesis. Although many researchers have conducted association studies between TGFB1 C-509T polymorphism and the risk of developing gastric cancer, the results are not uniform.
METHODS We genotyped 1028 gastric cancer patients and 958 controls by the polymerase chain reaction-restriction fragment length polymorphism method. Immunohistochemistry was performed to assess the expression of TGF-β1 in the cancer and noncancerous tissues of 120 gastric cancer patients. mRNA expression was also measured in noncancerous gastric mucosa by qRT-PCR in the 282 subjects.
RESULTS The CT genotype in the TGFB1 C-509T polymorphism was associated with an increased risk of gastric cancer development (adjusted OR 1.35, 95 % CI 1.07-1.71, P = 0.013), especially for intestinal-type cancer (adjusted OR 1.43, 95 % CI 1.08-1.90, P = 0.014). More frequent TGF-β1 expression was found in the center of cancer tissue in the TGFB1-509T carrier group than in the others (90.5 % vs. 72.2 %, P = 0.010). T-carriers also presented higher expression level of gastric TGF-β1 mRNA than non T-carriers (median 1.29 vs. 0.80, P = 0.004) when they were infected by H. pylori. Cancer patients showed elevated gastric TGFB1gene expression compared to the control group (median 1.22 vs. 0.89, P = 0.009).
CONCLUSIONS The carcinogenic effect of TGF-β1 might be associated with increased gastric TGF-β1 expression in subjects with the T allele of TGFB1-509.
- 1472015
제1저자 E. Van Cutsem, 방영주 · 교신저자 E. Van Cutsem
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HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer.Gastric Cancer. 2015;18(3):476-84.
PubMed IF 6.1 혈액종양내과Abstract
BACKGROUND In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors.
METHODS HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed.
RESULTS The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %.
CONCLUSIONS HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.
- 1462015
제1저자 문민경, 정인경 · 교신저자 박영주
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Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance.J Endocrinol. 2015;226(1):35-42.
PubMed IF 5.7 내분비대사내과Abstract
Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs. 97.9±18.2 mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.
- 1452015
제1저자 유병수, 박진주 · 교신저자 최동주
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Prognostic value of hyponatremia in heart failure patients: an analysis of the Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (COAST) study.Korean J Intern Med. 2015;30(4):460-70.
PubMed IF 2.2 순환기내과Abstract
BACKGROUND/AIMS Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients.
METHODS The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients.
RESULTS The mean admission sodium level was 138 ± 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na(+) < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and β-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients.
CONCLUSIONS In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts.
- 1442015
제1저자 박완범 · 교신저자 명선정
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Does Objective Structured Clinical Examinations Score Reflect the Clinical Reasoning Ability of Medical Students?Am J Med Sci. 2015;350(1):64-7.
PubMed IF 2.4 감염내과Abstract
BACKGROUND Clinical reasoning ability is an important factor in a physician's competence and thus should be taught and tested in medical schools. Medical schools generally use objective structured clinical examinations (OSCE) to measure the clinical competency of medical students. However, it is unknown whether OSCE can also evaluate clinical reasoning ability. In this study, the authors investigated whether OSCE scores reflected students' clinical reasoning abilities.
METHODS Sixty-five fourth-year medical students participated in this study. Medical students completed the OSCE with 4 cases using standardized patients. For assessment of clinical reasoning, students were asked to list differential diagnoses and the findings that were compatible or not compatible with each diagnosis. The OSCE score (score of patient encounter), diagnostic accuracy score, clinical reasoning score, clinical knowledge score and grade point average (GPA) were obtained for each student, and correlation analysis was performed.
RESULTS Clinical reasoning score was significantly correlated with diagnostic accuracy and GPA (correlation coefficient = 0.258 and 0.380; P = 0.038 and 0.002, respectively) but not with OSCE score or clinical knowledge score (correlation coefficient = 0.137 and 0.242; P = 0.276 and 0.052, respectively). Total OSCE score was not significantly correlated with clinical knowledge test score, clinical reasoning score, diagnostic accuracy score or GPA.
CONCLUSIONS OSCE score from patient encounters did not reflect the clinical reasoning abilities of the medical students in this study. The evaluation of medical students' clinical reasoning abilities through OSCE should be strengthened.
- 1432015
제1저자 조남한 · 교신저자 임수
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High Blood Pressure and Its Association With Incident Diabetes Over 10 Years in the Korean Genome and Epidemiology Study (KoGES).Diabetes Care. 2015;38(7):1333-8.
PubMed IF 22.6 내분비대사내과Abstract
OBJECTIVE No prospective, community-based cohort studies have investigated the association between blood pressure and diabetes in Asian ethnicity. We investigated this issue in a 10-year prospective, community-based study of Koreans.
RESEARCH DESIGN AND METHODS We studied whether high blood pressure was associated with the development of diabetes in a population-based cohort, where we sampled ∼5,000 random subjects each from rural and urban areas (age range 40-69 years) during 2001-2010. Among 10,038 subjects, 8,359 without diabetes at baseline were categorized into normal (n = 4,809), prehypertension (n = 2,141), stage 1 hypertension (n = 804), and stage 2 hypertension (n = 605) groups, according to their blood pressure readings of <120/80 mmHg, 120-139/80-89 mmHg, 140-159/90-99 mmHg, and ≥160/100 mmHg, respectively. The development of diabetes was defined as a fasting glucose concentration of ≥126 mg/dL or a postload glucose concentration of ≥200 mg/dL, based on a 75-g oral glucose tolerance test, or the use of antidiabetic medication.
RESULTS During the 10-year follow-up period, diabetes developed in 1,195 subjects (14.3%). The incidence of diabetes increased from 11.1% in the normal group to 17.0% in the prehypertension group, 17.7% in the stage 1 hypertension group, and 25.8% in the stage 2 hypertension group (P < 0.001). After adjusting for anthropometric factors; family history of diabetes; biochemical parameters including C-reactive protein, A1C, and fasting glucose and postload 2-h glucose levels; and the use of lipid-lowering medications, the hazard risks of diabetes development were 1.23 (95% CI 1.06-1.42), 1.26 (1.04-1.54), and 1.60 (1.30-1.96), respectively, in the prehypertension, stage 1 hypertension, and stage 2 hypertension groups.
CONCLUSIONS Our findings indicate a grade association of baseline blood pressure with the development of diabetes in Korean individuals.
- 1422015
제1저자 문승욱 · 교신저자 김진원
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p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines.Cancer Res Treat. 2015;47(3):501-8.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets.
MATERIALS AND METHODS Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA.
RESULTS Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine.
CONCLUSION PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.
- 1412015
제1저자 구영도 · 교신저자 박경수
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SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle.Diabetes. 2015;64(7):2420-31.
PubMed IF 9.3 내분비대사내과Abstract
Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-κB-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR)δ and PPARγ, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet-induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders.
- 1402015
제1저자 오태정 · 교신저자 조영민
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Correlation of the incretin effect with first- and second-phase insulin secretions in Koreans with various glucose tolerance statuses.Clin Endocrinol (Oxf). 2015;83(1):59-66.
PubMed IF 2.8 내분비대사내과Abstract
OBJECTIVE To examine the relationship between beta-cell function and the incretin effect.
DESIGN We performed a 180-min hyperglycaemic clamp study with oral glucose administration at 60 min in Korean subjects with normal glucose tolerance (NGT, n = 9), impaired fasting glucose (IFG, n = 6) and type 2 diabetes mellitus (T2DM, n = 6).
MEASUREMENTS First- and second-phase insulin secretions were measured during the first 60 min. The insulin response to intravenous glucose during the 60- to 120-min interval (Insiv) was calculated using a prediction method. The insulin response to oral glucose (Ins(oral)) was calculated by subtracting the Insiv from the overall insulin response during the 60- to 120-min interval (Ins(overall)). The incretin effect under the hyperglycaemic clamp condition (IE(clamp)) was calculated by the equation: 100 × [(Ins(overall) - Insiv)/Ins(overall)].
RESULTS The IE(clamp) was comparable among the three groups (46.3 ± 6.4%, 35.7 ± 8.8% and 51.4 ± 7.4% for the NGT, IFG and T2DM group, respectively, P = 0.327) and was not correlated with the first- and second-phase insulin secretions. However, the Ins(oral) (mU/l 60 min) was significantly different between the NGT, IFG and T2DM groups (5199 ± 1185, 2164 ± 956 and 1034 ± 355, respectively; P = 0.010) and was well correlated with the first- and second-phase insulin secretions.
CONCLUSIONS The incretin effect measured by the hyperglycaemic clamp with oral glucose loading was neither correlated with beta-cell function nor different between NGT, IFG and T2DM groups in Koreans.
- 1392015
제1저자 조선욱, 강아름 · 교신저자 박영주
, , , , , , , , , , , ,
The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131)I dose over 37 GBq.Clin Endocrinol (Oxf). 2015;83(1):117-23.
PubMed IF 2.8 내분비대사내과Abstract
BACKGROUND The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC).
METHODS A total of 2468 DTC patients who underwent thyroidectomy were reviewed. SPM was defined as a non-thyroidal malignancy, diagnosed at least 1 year after the diagnosis of thyroid cancer. Patients were divided into five groups according to cumulative (131)I dose: very high-activity (≥ 37.0 GBq), high-activity (22.3-36.9 GBq), intermediate-activity (5.56-22.2 GBq), low-activity (1.1-5.55 GBq) and no RAI.
RESULTS Among the 2468 patients, 61 (2.5%) had SPMs during 7.0 (1.0-33.0) years of median follow-up. Age above 40 years, male sex and very high-activity RAI were independent risk factors for the development of SPM. SPM-related mortality was highest in the very high-activity group, while DTC-related mortality was highest in the high-activity group. The overall mortality both from SPM and DTC was highest in the high-activity group.
CONCLUSION A cumulative (131)I dose <37.0 GBq did not increase the risk of SPM. A cumulative (131) I dose ≥ 37.0 GBq increased the risk of SPM and SPM-related mortality and decreased the DTC-specific mortality, resulting in a similar all-cause mortality compared with the low-activity RAI group. Using repeated high-dose RAI for treating RAI-responsive but persistent DTC patients needs careful consideration of the individual benefits from RAI vs the risk of developing SPM.
- 1382015
제1저자 김현숙 · 교신저자 이정표
, , , , , , , , , , ,
Elderly Peritoneal Dialysis Compared with Elderly Hemodialysis Patients and Younger Peritoneal Dialysis Patients: Competing Risk Analysis of a Korean Prospective Cohort Study.PLoS One. 2015;10(6):e0131393.
PubMed IF 2.8 신장내과Abstract
The outcomes of peritoneal dialysis (PD) in elderly patients have not been thoroughly investigated. We aimed to investigate the clinical outcomes and risk factors associated with PD in elderly patients. We conducted a prospective observational nationwide adult end-stage renal disease (ESRD) cohort study in Korea from August 2008 to March 2013. Among incident patients (n = 830), patient and technical survival rate, quality of life, and Beck's Depression Inventory (BDI) scores of elderly PD patients (≥65 years, n = 95) were compared with those of PD patients aged ≤49 years (n = 205) and 50~64 years (n = 192); and elderly hemodialysis (HD) patients (n = 315). The patient death and technical failure were analyzed by cumulative incidence function. Competing risk regressions were used to assess the risk factors for survival. The patient survival rate of elderly PD patients was inferior to that of younger PD patients (P<0.001). However, the technical survival rate was similar (P = 0.097). Compared with elderly HD patients, the patient survival rate did not differ according to dialysis modality (P = 0.987). Elderly PD patients showed significant improvement in the BDI scores, as compared with the PD patients aged ≤49 years (P = 0.003). Low albumin, diabetes and low residual renal function were significant risk factors for the PD patient survival; and peritonitis was a significant risk factor for technical survival. Furthermore, low albumin and hospitalization were significant risk factors of patient survival among the elderly. The overall outcomes were similar between elderly PD and HD patients. PD showed the benefit in BDI and quality of life in the elderly. Additionally, the technical survival rate of elderly PD patients was similar to that of younger PD patients. Taken together, PD may be a comparable modality for elderly ESRD patients.
- 1372015
제1저자 조은주 · 교신저자 이정훈
, , , , , , , , , ,
Comparison of the Efficacy of Entecavir and Tenofovir in Nucleos(T)ide Analogue-Experienced Chronic Hepatitis B Patients.PLoS One. 2015;10(6):e0130392.
PubMed IF 2.8 소화기내과Abstract
The efficacy of entecavir (ETV) and tenofovir (TDF) for the treatment of nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients has been little studied. Here, we compare the efficacy of both ETV and TDF in NA-experienced CHB patients without detectable genotypic resistance. This retrospective cohort study included consecutive NA-experienced patients who had neither current nor previous genotypic resistance and had received ETV or TDF for at least 6 months. Overall, 202 patients (146 patients in the ETV group and 56 in the TDF group) were analyzed. The cumulative probabilities of complete virologic suppression (CVS) at month 12 were 76.1% in the ETV group and 95.0% in the TDF group (P<0.001), respectively. The TDF-treated group achieved CVS more rapidly than the ETV group for both Hepatitis B e antigen (HBeAg)-negative and -positive patients (P = 0.006 and < 0.001, respectively), and for those with both low (< 2,000 IU/mL) and high (≥ 2,000 IU/mL) HBV DNA levels (P = 0.01 and 0.002, respectively). TDF group had an increased probability of achieving CVS (hazard ratio, 2.242; 95% confidence interval, 1.587-3.165; P = 0.001), after adjustment for HBV DNA level, the presence of HBeAg, and a history of CVS during prior treatment. During the treatment period, 23 patients (15.8%) in the ETV group developed virologic breakthrough, compared to none in the TDF group. The cumulative probabilities of developing virologic breakthrough and ETV-resistance at month 24 were 9.7% and 5.3%, respectively. In conclusion, TDF is preferable to ETV for achieving CVS in NA-experienced CHB patients without genotypic resistance.
- 1362015
제1저자 이재민 · 교신저자 이상협
, , , , , , , ,
Risk factors of organ failure in cholangitis with bacteriobilia.World J Gastroenterol. 2015;21(24):7506-13.
PubMed IF 7.7 소화기내과Abstract
AIM To identify the risk factors for organ failure (OF) in cholangitis with bacteriobilia.
METHODS This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage between January 2005 and April 2013. We conducted a retrospective analysis of comprehensive clinical and laboratory data.
RESULTS There were 24 cases (13.2%) of OF and five deaths (2.7%). Bile culture was positive for microbial growth in 130 out of 138 (94.2%) patients. In multivariate analysis of 130 patients with positive bile cultures, significant predictive factors for OF were the presence of extended-spectrum beta-lactamase (ESBL) organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis as an etiology, with odds ratios of 15.376, 6.319, and 3.573, respectively. We developed a scoring system with a regression coefficient of each significant variable. The OF score was calculated using the following equation: (2.7 × ESBL organisms in blood cultures) + (1.8 × pre-existing renal dysfunction) + (1.3 × choledocholithiasis). This scoring system for predicting OF was highly specific (99.1%) and had a positive predictive value of 86.2%.
CONCLUSION ESBL organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis are risk factors for OF in cholangitis with bacteriobilia. The OF scoring system may aid clinicians to identify a poor prognosis group.
- 1352015
제1저자 안정남 · 교신저자 임춘수
, , , , , , , , , , ,
The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial.PLoS One. 2015;10(6):e0128632.
PubMed IF 2.8 신장내과Abstract
Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.
- 1342015
제1저자 서지연 · 교신저자 이동호
, , , , , , , ,
Clinicopathologic and molecular features associated with patient age in gastric cancer.World J Gastroenterol. 2015;21(22):6905-13.
PubMed IF 7.7 소화기내과Abstract
AIM To compare characteristics and prognosis of gastric cancer based on age.
METHODS A retrospective study was conducted on clinical and molecular data from patients (n = 1658) with confirmed cases of gastric cancer in Seoul National University Bundang Hospital (Seoul, South Korea) from 2003 to 2010 after exclusion of patients diagnosed with lymphoma, gastrointestinal stromal tumor, and metastatic cancer in the stomach. DNA was isolated from tumor and adjacent normal tissue, and a set of five markers was amplified by polymerase chain reaction to assess microsatellite instability (MSI). MSI was categorized as high, low, or stable if ≥ 2, 1, or 0 markers, respectively, had changed. Immunohistochemistry was performed on tissue sections to detect levels of expression of p53, human epidermal growth factor receptor (HER)-2, and epidermal growth factor receptor. Statistical analysis of clinical and molecular data was performed to assess prognosis based on the stratification of patients by age (≤ 45 and > 45 years).
RESULTS Among the 1658 gastric cancer patients, the number of patients with an age ≤ 45 years was 202 (12.2%; 38.9 ± 0.4 years) and the number of patients > 45 years was 1456 (87.8%; 64.1 ± 0.3 years). Analyses revealed that females were predominant in the younger group (P < 0.001). Gastric cancers in the younger patients exhibited more aggressive features and were at a more advanced stage than those in older patients. Precancerous lesions, such as atrophic gastritis and intestinal metaplasia, were observed less frequently in the older than in the younger group (P < 0.001). Molecular characteristics, including overexpression of p53 (P < 0.001), overexpression of HER-2 (P = 0.006), and MSI (P = 0.006), were less frequent in gastric cancer of younger patients. Cancer related mortality was higher in younger patients (P = 0.048), but this difference was not significant after adjusting for the stage of cancer.
CONCLUSION Gastric cancer is distinguishable between younger and older patients based on both clinicopathologic and molecular features, but stage is the most important predictor of prognosis.
- 1332015
제1저자 구유정 · 교신저자 임수
, , , , , , , , , ,
Four-Year Durability of Initial Combination Therapy with Sitagliptin and Metformin in Patients with Type 2 Diabetes in Clinical Practice; COSMIC Study.PLoS One. 2015;10(6):e0129477.
PubMed IF 2.8 내분비대사내과Abstract
OBJECTIVES We investigated the efficacy of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes for 4 years in clinical practice.
METHODS Between 2009 and 2010, we reviewed 1,178 patients with type 2 diabetes (HbA1c ≥7.5% or 58 mmol/mol) prescribed initial combination therapy with sitagliptin and metformin. After excluding 288 patients without a second follow-up, 890 individuals (age, 58.0 ± 12.5 years; BMI, 25.4 ± 3.5 kg/m2; HbA1c, 8.6 ± 1.1%) were followed up with every 3-6 months for 4 years. Homeostasis model assessments for insulin resistance and β-cell function (HOMA-β) were recorded at baseline. The response criterion was HbA1c reduction by ≥0.8% from baseline or attainment of the target HbA1c (≤7.0% or 53 mmol/mol). At the end of every year of treatment, changes in HbA1c from the baseline were assessed.
RESULTS After 1 year, 72.2% of patients with initial combination therapy had responded, defined as HbA1c reduction ≥0.8% or attainment of the target HbA1c ≤7.0%. After 4 years, 35.4% of the patients still showed a response, with an HbA1c level of 7.0 ± 0.9%. A high HbA1c level at baseline was the most significant independent predictor of the long-term response (P<0.001). In addition, low HOMA-β was a significant predictor of a greater reduction in HbA1c. This treatment was generally well tolerated over the 4-year follow-up period, without any serious adverse events.
CONCLUSIONS This real-world follow-up study shows a persistent glucose-reducing effect of initial combination therapy with sitagliptin and metformin for up to 4 years.
- 1322015
제1저자 백선하 · 교신저자 진호준
, , , , , , , ,
Outcomes of predialysis nephrology care in elderly patients beginning to undergo dialysis.PLoS One. 2015;10(6):e0128715.
PubMed IF 2.8 신장내과Abstract
BACKGROUND The proportion of elderly patients beginning to undergo dialysis is increasing globally. Whether early referral (ER) of elderly patients is associated with favorable outcomes remains under debate. We investigated the influence of referral timing on the mortality of elderly patients.
METHODS We retrospectively assessed mortality in 820 patients aged ≥70 years with end-stage renal disease (ESRD) who initiated hemodialysis at a tertiary university hospital between 2000 and 2010. Mortality data was obtained from the time of dialysis initiation until December 2010. We assigned patients to one of two groups according to the time of their first encounters with nephrologists: ER (≥ 3 months) and late referral (LR; < 3 months).
RESULTS During a mean follow-up period of 25.1 months, the ER group showed a 24% reduced risk of long-term mortality relative to the LR group (HR = 0.760, P = 0.009). Rate of reduction in 90-day mortality for ER patients was 58% (HR = 0.422, P=0.012). However, the statistical significance of the difference in mortality rates between ER and LR group was not observed across age groups after 90 days. Old age, LR, central venous catheter, high white blood cell count and corrected Ca level, and lower levels of albumin, creatinine, hemoglobin, and sodium were significantly associated with increased risk of mortality.
CONCLUSIONS Timely referral was also associated with reduced mortality in elderly ESRD patients who initiated hemodialysis. In particular, the initial 90-day mortality reduction in ER patients contributed to mortality differences during the follow-up period.
- 1312015
제1저자 이정훈, 이준혁 · 교신저자 윤정환
, , , , , , , , , ,
Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma.Gastroenterology. 2015;148(7):1383-91.e6.
PubMed IF 29.7 소화기내과Abstract
BACKGROUND & AIMS No adjuvant therapy has been shown to extend the survival of patients with hepatocellular carcinoma (HCC) receiving curative treatment. We investigated whether injections of activated cytokine-induced killer (CIK) cells (CD3+/CD56+ and CD3+/CD56- T cells and CD3-/CD56+ natural killer cells) prolongs recurrence-free survival of patients after curative therapy for HCC.
METHODS We performed a multicenter, randomized, open-label, phase 3 trial of the efficacy and safety of adjuvant immunotherapy with activated CIK cells (created by incubation of patients' peripheral blood mononuclear cells with interleukin 2 and an antibody against CD3). The study included 230 patients with HCC treated by surgical resection, radiofrequency ablation, or percutaneous ethanol injection at university-affiliated hospitals in Korea. Patients were assigned randomly to receive immunotherapy (injection of 6.4 × 10(9) autologous CIK cells, 16 times during 60 weeks) or no adjuvant therapy (controls). The primary end point was recurrence-free survival; secondary end points included overall survival, cancer-specific survival, and safety.
RESULTS The median time of recurrence-free survival was 44.0 months in the immunotherapy group and 30.0 months in the control group (hazard ratio with immunotherapy, 0.63; 95% confidence interval [CI], 0.43-0.94; P = .010 by 1-sided log-rank test). Hazard ratios also were lower in the immunotherapy than in the control group for all-cause death (0.21; 95% CI, 0.06-0.75; P = .008) and cancer-related death (0.19; 95% CI, 0.04-0.87; P = .02). A significantly higher proportion of patients in the immunotherapy group than in the control group had an adverse event (62% vs 41%; P = .002), but the proportion of patients with serious adverse events did not differ significantly between groups (7.8% vs 3.5%; P = .15).
CONCLUSIONS In patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. ClinicalTrials.gov number: NCT00699816.
- 1302015
제1저자 조유리 · 교신저자 김윤준
, , , , ,
Comparison of the efficacies of entecavir 0.5 and 1.0 mg combined with adefovir in patients with chronic hepatitis B who had failed on prior nucleos(t)ide analogue treatments.J Med Virol. 2015;87(6):999-1007.
PubMed IF 3.7 소화기내과Abstract
Entecavir (ETV) plus adefovir (ADV) combination therapy is one of the useful treatment option for the patients with chronic hepatitis B (CHB) who had failed on prior nucleos(t) ide analogue (NA) treatments. This study compared the efficacies of the combinations of ETV 0.5 mg plus ADV and ETV 1.0 mg plus ADV in patients who had failed on prior multiple NA treatments. This retrospective analysis included 148 consecutive patients with CHB infection in Korea (n = 37 with ETV 0.5 mg plus ADV and n = 111 with ETV 1.0 mg plus ADV). The virological and biochemical responses were compared between the two groups. The cumulative probability of viral suppression of ETV 0.5 mg plus ADV was not inferior to that of ETV 1.0 mg plus ADV (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.38-1.08; P = 0.094). The changes in serum HBV DNA level in the ETV 0.5 mg plus ADV group were not different between the two groups over 12 months. Moreover, no significant difference was observed in acquiring ETV-resistant variants between the two groups during the treatment (HR, 0.95; P = 0.953). This study suggests the proof-of-concept that the lower dose of NA in combination with other NA might be the theoretical option for rescue combination therapy in patients with CHB who had failed on prior multiple NA treatments in order to reduce systemic exposure and possible side effects of NA.
- 1292015
제1저자 최홍미 · 교신저자 김형관
, , , , , , , , , ,
Myocardial fibrosis progression on cardiac magnetic resonance in hypertrophic cardiomyopathy.Heart. 2015;101(11):870-6.
PubMed IF 4.4 순환기내과Abstract
OBJECTIVE We hypothesised that, in hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is progressive and can be predicted by baseline CMR findings and HCM phenotype.
METHODS In this single-centre cohort study, 71 patients with HCM (59±13 years; 48 men) were prospectively enrolled with clinical, echocardiographic and CMR data. Two consecutive CMR scans were performed with a time interval of 582±174 days. The LGE extent was quantified as a proportion of total LV myocardium (%LGE).
RESULTS LGE was present in 65 patients (91.5%) at the first CMR (CMR-1). In all, LGE extent was significantly increased (p<0.001). A difference in %LGE between the two CMR scans was correlated with the initial %LGE (r=0.44, p<0.001). LGE progression, defined as >4% increase in LGE at the second CMR, was present in 19 patients with non-apical HCM (36.5%), but in only one apical HCM (5.3%). Also, LGE progression rate was significantly higher in non-apical (0.15%/month) versus apical HCM (0.025%/month) (p=0.001). On the multivariate model #1 including only clinical variables (age, history of paroxysmal atrial fibrillation, LV outflow tract obstruction on echocardiography, beta-blocker use, family history of sudden death, family history of HCM, syncope, non-sustained ventricular tachycardia, rate pressure product, and HCM phenotype), only apical HCM phenotype was associated with less LGE progression (p=0.038). On the multivariate model #2 including CMR variables additional to the model #1, %LGE at CMR-1 was the only determinant for LGE progression (p=0.007). When the analysis was limited to patients with preserved EF, results remained unchanged.
CONCLUSIONS Myocardial fibrosis in HCM is a progressive phenomenon. Non-apical phenotype and a higher LGE extent at CMR-1 are both associated with greater LGE progression.
- 1282015
제1저자 노은, 곽수헌 · 교신저자 박경수
, , , , , , ,
Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes.Acta Diabetol. 2015;52(3):489-95.
PubMed IF 3.1 내분비대사내과Abstract
AIMS Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated nuclear transcription factor. There are limited studies about the association of serum AhR ligand activities and T2DM. Our objective was to investigate the association of serum AhR ligand activities with T2DM and its related metabolic parameters.
METHODS This case-control study involved 83 subjects with T2DM as well as age-, sex-, and body mass index (BMI)-matched subjects with impaired glucose tolerance (IGT, n = 130) and normal glucose tolerance (NGT, n = 83). Serum AhR ligand activities were measured using a cell-based AhR ligand assay and standardized as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l).
RESULTS The T2DM group had the highest AhR ligand activities compared to the IGT and NGT groups [median (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1, 63.7) pmol/l, respectively; P = 0.003]. In the multivariate analysis, the log2-transformed TCDDeq levels were significantly associated with the risk of T2DM after adjusting for age, sex, and BMI (odds ratio 2.26, 95 % confidence interval 1.34-3.82; P = 0.002). In nondiabetic subjects, serum AhR ligand activities showed a positive correlation with fasting glucose and insulin concentrations and the homeostasis model assessment of insulin resistance, but showed a negative correlation with adiponectin concentrations.
CONCLUSIONS Serum AhR ligand activities were higher in the T2DM group and were correlated with the parameters of insulin resistance. Further investigation is required to elucidate the causal relationship between AhR ligand activity and T2DM.
- 1272015
제1저자 송우정 · 교신저자 장윤석
, , , , , , , , , , ,
Urban-rural differences in the prevalence of allergen sensitization and self-reported rhinitis in the elderly population.Ann Allergy Asthma Immunol. 2015;114(6):455-61.
PubMed IF 7.1 알레르기내과Abstract
BACKGROUND Urbanization is frequently associated with allergic conditions during childhood; however, the literature lacks studies on the association between allergies and degree of urbanization in the elderly population.
OBJECTIVE To determine how the degree of urbanization affects the prevalence of allergic sensitization and self-reported rhinitis symptoms in elderly community populations.
METHODS The study population consisted of 1,311 elderly subjects identified from 2 community population cohort datasets who were divided into 3 groups according to the degree of urbanization (urban, semirural, and rural) where they resided. Current rhinitis symptoms were assessed using a questionnaire. Sensitization to inhalant allergen was measured using skin prick tests for 9 common allergens.
RESULTS Sensitization to inhalant allergen showed a positive correlation with degree of urbanization (urban 17.2%, semirural 9.8%, rural 6.0%; P for trend <.001), with a significant correlation observed between house dust mite allergens and degree of urbanization. Self-reported rhinitis symptoms were mostly nonallergic, but showed a positive correlation with degree of urbanization (urban 26.8%, semirural 18.2%, rural 11.5%; P for trend <.001). Self-reported rhinoconjunctivitis also correlated with urbanization. Correlations between self-reported allergic conditions and urbanization remained statistically significant in multivariate logistic regression tests.
CONCLUSION The present analyses found significant correlations between degree of urbanization with self-reported rhinitis symptoms and sensitization to inhalant allergen in the elderly population. These findings warrant further investigation of the roles that urban factors play in the development of elderly rhinitis and allergen sensitization.
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