SCI 발표논문

1. 372016

   제1저자 오윤규 · 교신저자 임춘수

   Oh YK, Yang CW, Kim YL, Kang SW, Park CW, Kim YS, Lee EY, Han BG, Lee SH, Kim SH, Lee H, Lim CS

   Clinical Characteristics and Outcomes of Renal Infarction.

   Am J Kidney Dis. 2016;67(2):243-50.

   Abstract

   BACKGROUND Renal infarction is a rare condition resulting from an acute disruption of renal blood flow, and the cause and outcome of renal infarction are not well established.

   STUDY DESIGN Case series.

   SETTING & PARTICIPANTS 438 patients with renal infarction in January 1993 to December 2013 at 9 hospitals in Korea were included. Renal infarction was defined by radiologic findings that included single or multiple wedge-shaped parenchymal perfusion defects in the kidney.

   PREDICTOR Causes of renal infarction included cardiogenic (n=244 [55.7%]), renal artery injury (n=33 [7.5%]), hypercoagulable (n=29 [6.6%]), and idiopathic (n=132 [30.1%]) factors.

   OUTCOMES We used recurrence, acute kidney injury (AKI; defined as creatinine level increase ≥ 0.3mg/dL within 48 hours or an increase to 150% of baseline level within 7 days during the sentinel hospitalization), new-onset estimated glomerular filtration rate (eGFR)<60mL/min/1.73m(2) (for >3 months after renal infarction in the absence of a history of decreased eGFR), end-stage renal disease (ESRD; receiving hemodialysis or peritoneal dialysis because of irreversible kidney damage), and mortality as outcome metrics.

   RESULTS Treatment included urokinase (n=19), heparin (n=342), warfarin (n=330), and antiplatelet agents (n=157). 5% of patients died during the initial hospitalization. During the median 20.0 (range, 1-223) months of follow-up, 2.8% of patients had recurrent infarction, 20.1% of patients developed AKI, 10.9% of patients developed new-onset eGFR<60mL/min/1.73m(2), and 2.1% of patients progressed to ESRD.

   LIMITATIONS This was a retrospective study; it cannot clearly determine the specific causal mechanism for certain patients or provide information about the causes of mortality. 16 patients were excluded from the prognostic analysis.

   CONCLUSIONS Cardiogenic origins were the most important causes of renal infarction. Despite aggressive treatment, renal infarction can lead to AKI, new-onset eGFR<60mL/min/1.73m(2), ESRD, and death.

   PubMed IF 9.4 신장내과
2. 362016

   제1저자 김경민 · 교신저자 최성희

   Kim KM, Lim S, Moon JH, Jin H, Jung KY, Shin CS, Park KS, Jang HC, Choi SH

   Lower uncarboxylated osteocalcin and higher sclerostin levels are significantly associated with coronary artery disease.

   Bone. 2016;83:178-183.

   Abstract

   Systemic roles for bone-derived proteins have emerged from recent studies. In particular, the serum concentration of osteocalcin (OCN) or sclerostin was found to be associated with altered glucose metabolism or atherosclerosis. The aims of this study were to evaluate OCN and sclerostin levels in subjects who underwent coronary artery bypass graft (CABG) surgery compared with those in normal controls and to analyze their relationships with atherosclerosis. This was an age- and sex-matched case-control study that included 61 male subjects who underwent CABG and 61 controls. Forty-six subjects (37.7%) with diabetes and 62 hypertensive subjects (50.8%) were included. Serum sclerostin, uncarboxylated OCN (ucOCN) and carboxylated OCN (cOCN) were measured. Coronary artery calcium (CAC) score was calculated according to Agatston's method, using a 64-slice multi-detector computed tomography scanner. The levels of serum ucOCN were significantly lower and sclerostin concentrations were higher in the CABG group than in the controls (p<0.05 for both), and these significances were maintained after adjusting for atherosclerotic risk factors in both diabetic and nondiabetic patients (p<0.05 in both groups). However, there was no difference in cOCN levels between CABG patients and controls. The group with abnormal CAC scores (CAC scores ≥100) had significantly higher levels of serum sclerostin (p<0.05). In multiple logistic regression analysis, both lower ucOCN and higher sclerostin levels were independently associated with CABG (odds ratio [OR] 0.43, 95% CI 0.22-0.84, p<0.05 for log(ucOCN); and OR 2.09, 95% CI 1.08-4.05, p<0.05 for log(sclerostin)). In subjects with CAD who underwent CABG, the serum ucOCN level was decreased and the sclerostin level was increased compared with those in the controls, regardless of diabetic status. Longitudinal studies are warranted to establish the precise roles of ucOCN and sclerostin in the pathogenesis of atherosclerosis.

   PubMed IF 3.9 내분비대사내과
3. 352016

   제1저자 임주현 · 교신저자 김나영

   Lim JH, Kim N, Lim SH, Kwon JW, Shin CM, Chang YS, Kim JS, Jung HC, Cho SH

   Inverse Relationship Between Helicobacter Pylori Infection and Asthma Among Adults Younger than 40 Years: A Cross-Sectional Study.

   Medicine (Baltimore). 2016;95(8):e2609.

   Abstract

   Recent studies have suggested that Helicobacter pylori could prevent allergic disease, particularly in children. However, whether this is true in adults is controversial. The aim of this study was to investigate whether there is negative association between H. pylori infection and asthma among adults in an area with a high prevalence of H. pylori.This was a cross-sectional study using 2011 health surveillance data. Blood samples were taken from all participants to measure serum H. pylori IgG status. Information on demographics, socioeconomic status, and medical history, including asthma and other allergic conditions were collected by a questionnaire.Of the 15,032 patients, 9492 (63.1%) had a history of H. pylori infection, 359 (2.4%) had asthma, and 3277 (21.8%) had other allergic conditions. H. pylori infection was positively correlated with age (OR, 1.050; 95% CI, 1.047-1.053, P < 0.001). Asthma history was positively correlated with age (OR, 1.022; 95% CI, 1.013-1.032, P < 0.001). H. pylori and age were shown to have interaction on asthma in the total participants (OR, 1.041; 95% CI, 1.021-1.062, P < 0.001). In subgroup analysis, H. pylori infection among those < 40 years old was inversely correlated with asthma (OR, 0.503; 95% CI, 0.280-0.904, P = 0.021). Other allergic conditions were not related with H. pylori infection among the total and those <40 years old.The inverse association between H. pylori infection and asthma among young adults suggests that the underlying immune mechanism induced by H. pylori infection may affect allergic reactions associated with asthma in young adults.

   PubMed IF 2 소화기내과
4. 342016

   제1저자 윤지연 · 교신저자 김태유

   Yun J, Song SH, Kang JY, Park J, Kim HP, Han SW, Kim TY

   Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability.

   Nucleic Acids Res. 2016;44(2):558-72.

   Abstract

   Gene amplification is a hallmark of cancer with chromosomal instability although the underlying mechanism by which altered copy numbers are maintained is largely unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle progression and transcriptional regulation of key developmental genes, is frequently overexpressed in human cancer. Here we show that cohesin-dependent change in DNA replication controls the copy numbers of amplified genes in cancer cells with chromosomal instability. We found that the down-regulation of elevated cohesin leads to copy number-associated gene expression changes without disturbing chromosomal segregation. Highly amplified genes form typical long-range chromatin interactions, which are stabilized by enriched cohesin. The spatial proximities among cohesin binding sites within amplified genes are decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene expression. After several passages, cohesin depletion inhibits DNA replication initiation by reducing the recruitment of pre-replication complexes such as minichromosome maintenance subunits 7 (MCM7), DNA polymerase α, and CDC45 at replication origins near the amplified regions, and as a result, decreases the DNA copy numbers of highly amplified genes. Collectively, our data demonstrate that cohesin-mediated chromatin organization and DNA replication are important for stabilizing gene amplification in cancer cells with chromosomal instability.

   PubMed IF 15 혈액종양내과
5. 332016

   제1저자 구현경 · 교신저자 이창훈

   Koo HK, Jin KN, Kim DK, Chung HS, Lee CH

   Association of incidental emphysema with annual lung function decline and future development of airflow limitation.

   Int J Chron Obstruct Pulmon Dis. 2016;11:161-6.

   Abstract

   OBJECTIVES Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities.

   MATERIALS AND METHODS Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below -950 Hounsfield units (%LAA-950) was calculated automatically. A calculated value of %LAA-950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models.

   RESULTS A total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (-33.9 versus -18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up.

   CONCLUSION Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed.

   PubMed IF 4.1 호흡기내과
6. 322016

   제1저자 홍아람, 김정희 · 교신저자 김상완, 김성연

   Hong AR, Kim JH, Song YS, Lee KE, Seo SH, Seong MW, Shin CS, Kim SW, Kim SY

   Genetics of Aldosterone-Producing Adenoma in Korean Patients.

   PLoS One. 2016;11(1):e0147590.

   Abstract

   OBJECTIVES Recently, somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes were found to be associated with the pathogenesis of aldosterone-producing adenoma (APA). This study aimed to investigate the prevalence of somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D and examine the correlations between these mutations and the clinical and biochemical characteristics in Korean patients with APA.

   METHODS We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes.

   RESULTS Somatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R); these two mutations were mutually exclusive. Somatic mutations in the ATP1A1, ATP2B3, and CACNA1D genes were not observed. Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030). Moreover, patients with KCNJ5 mutations comprised a significantly higher proportion of patients younger than 35 years of age (19.1% versus 0%, respectively; P = 0.040). There were no significant differences in pre-operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status. Patients with KCNJ5 mutations were less likely to need antihypertensive medications after adrenalectomy compared with those without mutation (36.2% versus 63.2%; P = 0.045).

   CONCLUSIONS The present study demonstrated the high prevalence of somatic KCNJ5 mutations in Korean patients with APA. Carriers of somatic KCNJ5 mutations were more likely to be female. Early diagnosis and better therapeutic outcomes were associated with somatic KCNJ5 mutations in APA.

   PubMed IF 2.8 내분비대사내과
7. 312016

   제1저자 이동화 · 교신저자 김상완

   Lee DH, Jung KY, Hong AR, Kim JH, Kim KM, Shin CS, Kim SY, Kim SW

   Femoral geometry, bone mineral density, and the risk of hip fracture in premenopausal women: a case control study.

   BMC Musculoskelet Disord. 2016;17:42.

   Abstract

   BACKGROUND The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women.

   METHODS The participants in this case-control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI-adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements.

   RESULTS The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 ± 0.123 vs. 0.899 ± 0.115, p <0.001 for the femoral neck BMD and 0.724 ± 0.120 vs. 0.923 ± 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group.

   CONCLUSIONS BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered.

   PubMed IF 2.8 내분비대사내과
8. 302016

   제1저자 이성우 · 교신저자 진호준

   Lee SW, Yu MY, Baek SH, Ahn SY, Kim S, Na KY, Chae DW, Chin HJ

   Glomerular Immune Deposits Are Predictive of Poor Long-Term Outcome in Patients with Adult Biopsy-Proven Minimal Change Disease: A Cohort Study in Korea.

   PLoS One. 2016;11(1):e0147387.

   Abstract

   BACKGROUND AND OBJECTIVES There has been little published information on risk factors for poor long-term outcome in adult biopsy-proven minimal change disease (MCD).

   METHODS Data from sixty-three adult, biopsy-proven primary MCD patients treated at a tertiary university hospital between 2003 and 2013 were analyzed. Baseline clinical and pathologic factors were assessed for the associations with composite outcome of creatinine doubling, end stage renal disease, or all-cause mortality.

   RESULTS During a median (interquartile) 5.0 (2.8-5.0) years, the composite outcome occurred in 11.1% (7/63) of patients. The rate of glomerular immune deposits was 23.8% (15/63). Patients with glomerular immune deposits showed a significantly lower urine protein creatinine ratio than those without deposits (P = 0.033). The rate of non-responders was significantly higher in patients with glomerular immune deposits than in those without deposits (P = 0.033). In patients with deposits, 26.7% (4/15) developed the composite outcome, while only 6.3% (3/48) developed the composite outcome among those without deposits (P = 0.049). In multivariate Cox proportional hazards regression analysis, the presence of glomerular immune deposits was the only factor associated with development of the composite outcome (hazard ratio: 2.310, 95% confidence interval: 1.031-98.579, P = 0.047).

   CONCLUSION Glomerular immune deposits were associated with increased risk of a composite outcome in adult MCD patients. The higher rate of non-responders in patients with deposits might be related to the poor outcome. Future study is needed.

   PubMed IF 2.8 신장내과
9. 292016

   제1저자 정희원 · 교신저자 김진원, 김기웅

   Jung HW, Kim JW, Han JW, Kim K, Kim JH, Kim KI, Kim CH, Kim KW

   Multidimensional Geriatric Prognostic Index, Based on a Geriatric Assessment, for Long-Term Survival in Older Adults in Korea.

   PLoS One. 2016;11(1):e0147032.

   Abstract

   The patient´s survival estimate is important for clinical decision-making, especially in frail patients with multimorbidities. We aimed to develop a multidimensional geriatric prognosis index (GPI) for 3- and 5-year mortality in community-dwelling elderly and to validate the GPI in a separate hospital-based population. The GPI was constructed using data for 988 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA) and cross-validated with 1109 patients who underwent a geriatric assessment at the Seoul National University Bundang Hospital (SNUBH). The GPI, with a total possible score of 8, included age, gender, activities of daily living, instrumental activities of daily living, comorbidities, mood, cognitive function, and nutritional status. During the 5-year observation period, 179 KLoSHA participants (18.1%) and 340 SNUBH patients (30.7%) died. The c-indices for 3- and 5-year mortality were 0.78 and 0.80, respectively, in the KLoSHA group and 0.73 and 0.80, respectively, in the SNUBH group. Positive linear trends were observed for GPI scores and both 3- and 5-year mortality in both groups. In conclusions, using common components of a geriatric assessment, the GPI can stratify the risk of 3- and 5-year mortality in Korean elderly people both in the community and hospital.

   PubMed IF 2.8 혈액종양내과
10. 282016

    제1저자 강시혁 · 교신저자 오세일

    Kang SH, Heo J, Oh IY, Kim J, Lim WH, Cho Y, Choi EK, Yi SM, Do Shin S, Kim H, Oh S

    Ambient air pollution and out-of-hospital cardiac arrest.

    Int J Cardiol. 2016;203:1086-92.

    Abstract

    BACKGROUND Sudden cardiac arrest is a leading cause of cardiovascular death. This study aimed at investigating the impact of short-term exposure to air pollutants on the incidence of OHCA.

    METHODS We identified OHCA cases that occurred in Seoul between 2006 and 2013 from the nationwide emergency medical service database. The association of the daily incidence of OHCA with air pollutants including PM2.5 (particles ≤ 2.5 μm in aerodynamic diameter), PM10, CO, O3, NO2, and SO2 was analyzed with the use of time-series and case-crossover analyses.

    RESULTS A total of 21,509 OHCAs of presumed cardiac origin were identified. An elevation in PM2.5 by 10 μg/m(3) at a moving average of lag 1 and 2 days was shown to increase the risk of OHCA by 1.30% (95% confidence intervals, 0.20-2.41%). An exposure-response relationship was present: the risk of OHCA increased significantly with even a mild elevation of PM2.5 (10-15 μg/m(3)) and further increased with higher levels. While PM10, NO2, CO, and SO2 also showed significant associations with OHCA in single-pollutant models, only PM2.5 remained significant after adjustment for other pollutants. Subgroup analyses showed male sex, advanced age, hypertension, diabetes, heart disease, and history of stroke were risk factors for OHCA in response to elevations in PM2.5.

    CONCLUSIONS This study showed that increased ambient levels of PM2.5 were significantly associated with increased risk of OHCA within 1 to 2 days of exposure, which had a dose-response relationship. Subjects with conventional cardiovascular risk factors were more susceptible to harm of PM2.5.

    PubMed IF 3.3 순환기내과
11. 272016

    제1저자 최연악 · 교신저자 오도연

    Choi Y, Oh DY, Park H, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Bang YJ

    More Accurate Prediction of Metastatic Pancreatic Cancer Patients' Survival with Prognostic Model Using Both Host Immunity and Tumor Metabolic Activity.

    PLoS One. 2016;11(1):e0145692.

    Abstract

    INTRODUCTION Neutrophil to lymphocyte ratio (NLR) and standard uptake value (SUV) by 18F-FDG PET represent host immunity and tumor metabolic activity, respectively. We investigated NLR and maximum SUV (SUVmax) as prognostic markers in metastatic pancreatic cancer (MPC) patients who receive palliative chemotherapy.

    METHODS We reviewed 396 MPC patients receiving palliative chemotherapy. NLR was obtained before and after the first cycle of chemotherapy. In 118 patients with PET prior to chemotherapy, SUVmax was collected. Cut-off values were determined by ROC curve.

    RESULTS In multivariate analysis of all patients, NLR and change in NLR after the first cycle of chemotherapy (ΔNLR) were independent prognostic factors for overall survival (OS). We scored the risk considering NLR and ΔNLR and identified 4 risk groups with different prognosis (risk score 0 vs 1 vs 2 vs 3: OS 9.7 vs 7.9 vs 5.7 vs 2.6 months, HR 1 vs 1.329 vs 2.137 vs 7.915, respectively; P<0.001). In PET cohort, NLR and SUVmax were independently prognostic for OS. Prognostication model using both NLR and SUVmax could define 4 risk groups with different OS (risk score 0 vs 1 vs 2 vs 3: OS 11.8 vs 9.8 vs 7.2 vs 4.6 months, HR 1 vs 1.536 vs 2.958 vs 5.336, respectively; P<0.001).

    CONCLUSIONS NLR and SUVmax as simple parameters of host immunity and metabolic activity of tumor cell, respectively, are independent prognostic factors for OS in MPC patients undergoing palliative chemotherapy.

    PubMed IF 2.8 혈액종양내과
12. 262016

    제1저자 박상돈 · 교신저자 김효수

    Park SD, Koo BK, Oh IY, Yoon CH, Park JJ, Yang HM, Park KW, Lee HY, Kang HJ, Kim HS

    Effects of celecoxib on vascular changes after coronary intervention: A serial volumetric intravascular ultrasound analysis from the mini-COREA randomized clinical trial.

    Int J Cardiol. 2016;202:240-3.

    PubMed IF 3.3 순환기내과
13. 252016

    제1저자 김정현 · 교신저자 김덕겸

    Kim J, Park JS, Cho YJ, Yoon HI, Lee JH, Lee CT, Lim HJ, Kim DK

    Predictors of prolonged stay in patients with community-acquired pneumonia and complicated parapneumonic effusion.

    Respirology. 2016;21(1):164-71.

    Abstract

    BACKGROUND AND OBJECTIVE Development of CPE in CAP is associated with prolonged hospital stay and it may increase the morbidity and mortality. We aimed to identify microbiological and clinical factors that predicate a prolonged hospital admission in patients treated with a tube thoracostomy to control CPE.

    METHODS This retrospective cohort included patients with CPE requiring chest tube drainage in a tertiary referral Korean hospital from 1 January 2004 to 30 July 2012. After dichotomous grouping according to the mean duration of hospital stay, clinical, laboratory and microbiological parameters were compared.

    RESULTS The final analysis included 158 patients with CPE. The majority were male (130, 85.0%), and the mean age was 62.8 years. The mean duration of hospital stay was 17.7 (±10.2) days. The mean duration of chest tube drainage was 9.6 (±6.7) days. Streptococcus viridans (48.4%) was the most common pathogen. Intrapleural fibrinolysis was performed in 85 (53.8%); additional tube insertion was needed in 40 (25.3%) patients. In the multivariate analysis after adjusting for covariates, a prolonged hospital stay was associated with fever (aOR: 3.42, P = 0.02), lower PaO2 (aOR: 4.89, P = 0.007) and haemoglobin (aOR: 4.90, P = 0.003) levels, and an increased blood neutrophil fraction (aOR: 3.83, P = 0.01) on admission as well as the identification of microbes in CPE (aOR: 4.14, P = 0.03), and ineffective pleural drainage (aOR: 3.28, P = 0.03).

    CONCLUSIONS This study suggests that physicians should note the clinical symptoms and laboratory findings of severe infection and effectiveness of pleural drainage to predicate which patients with a CAP needing thoracostomy for CPE will have a prolonged hospital stay.

    PubMed IF 7.2 호흡기내과
14. 242016

    제1저자 최연악 · 교신저자 오도연

    Choi Y, Kim TY, Oh DY, Lee KH, Han SW, Im SA, Kim TY, Bang YJ

    The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy.

    Cancer Res Treat. 2016;48(1):171-9.

    Abstract

    PURPOSE A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear.

    MATERIALS AND METHODS We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years' duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).

    RESULTS Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044).

    CONCLUSION For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

    PubMed IF 4.2 혈액종양내과
15. 232016

    제1저자 오도연 · 교신저자 방영주

    Oh DY, Kim TM, Han SW, Shin DY, Lee YG, Lee KW, Kim JH, Kim TY, Jang IJ, Lee JS, Bang YJ

    Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors.

    Cancer Res Treat. 2016;48(1):28-36.

    Abstract

    PURPOSE CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors.

    MATERIALS AND METHODS Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1.

    RESULTS Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m(2)/day (n=3), 2 mg/m(2)/day (n=3), 3.3 mg/m(2)/day (n=3), 5 mg/m(2)/day (n=3), 7 mg/m(2)/day (n=3), 9 mg/m(2)/day (n=6), and 12 mg/m(2)/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m(2)/day. The MTD was determined as 12 mg/m(2)/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days).

    CONCLUSION This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m(2)/day on D1 and D8 every 3 weeks.

    PubMed IF 4.2 혈액종양내과
16. 222016

    제1저자 유경돈 · 교신저자 이하정

    Yoo KD, Kang S, Choi Y, Yang SH, Heo NJ, Chin HJ, Oh KH, Joo KW, Kim YS, Lee H

    Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function.

    Am J Kidney Dis. 2016;67(1):79-88.

    Abstract

    BACKGROUND High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels.

    STUDY DESIGN Observational cohort study.

    SETTING & PARTICIPANTS Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded.

    PREDICTOR Sex-specific quartiles of serum phosphorus and sex.

    OUTCOMES All-cause mortality.

    RESULTS The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs. lowest quartile, 1.34; 95% CI, 1.15-1.56; P<0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 [95% CI, 1.22-1.68] vs. 1.01 [95% CI, 0.76-1.33]), but interaction by sex was not significant (P=0.8).

    LIMITATIONS A single phosphorus measurement and low power to test for interactions by sex and age.

    CONCLUSIONS We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.

    PubMed IF 9.4 신장내과
17. 212016

    제1저자 정광현 · 교신저자 이상협

    Chung KH, Lee SH, Park JM, Lee JM, Shin CM, Ahn SH, Park do J, Kim HH, Ryu JK, Kim YT

    Partially covered self-expandable metallic stent for postoperative benign strictures associated with laparoscopy-assisted gastrectomy.

    Gastric Cancer. 2016;19(1):280-6.

    Abstract

    BACKGROUND A partially covered self-expandable metallic stent (PCSEMS) is of proven benefit in palliation of unresectable or inoperable malignant gastric outlet obstruction. However, its use in patients with benign anastomotic stricture after laparoscopy-assisted gastrectomy (LAG) is not well established.

    METHODS Patients who between May 2007 and June 2012 underwent PCSEMS placement for management of benign gastrointestinal obstruction after LAG were included in this retrospective analysis. The primary outcomes were the technical success and clinical success of the PCSEMS. The secondary outcomes were procedure-related complications and PCSEMS dysfunction.

    RESULTS Eleven patients (six women, five men, mean age 53.5 years, range 15-76 years) underwent successful placement of a PCSEMS for management of benign anastomotic strictures after LAG and were followed-up for a mean of 20.6 months (range 7.9-55.6 months). The mean gastric outlet obstruction scoring system (GOOSS) score was 0.36 before PCSEMS placement and 1.55 (p = 0.010) 24-48 h after PCSEMS placement. All of the patients were able to tolerate a solid diet (GOOSS score 3) after 1 week. There were no major or minor procedure-related complications. Stent dysfunction occurred in four patients (three distal migrations, one proximal migration), and stent removal was successful in all of the remaining patients after a mean of 2.0 months (1.1-3.0 months). Obstructive symptoms recurred in two patients (one after proximal migration, one after stent removal) and were treated successfully with PCSEMS reinsertion and balloon dilation.

    CONCLUSIONS A PCSEMS may be a feasible and effective option for management of benign anastomotic strictures after LAG which could avoid secondary surgery.

    PubMed IF 6.1 소화기내과
18. 202016

    제1저자 이상언 · 교신저자 구본권

    Lee SE, Yu CW, Park K, Park KW, Suh JW, Cho YS, Youn TJ, Chae IH, Choi DJ, Jang HJ, Park JS, Na SH, Kim HS, Kim KB, Koo BK

    Physiological and clinical relevance of anomalous right coronary artery originating from left sinus of Valsalva in adults.

    Heart. 2016;102(2):114-9.

    Abstract

    OBJECTIVE To examine physiological and clinical relevance of an anomalous right coronary artery originating from left sinus of Valsalva (right ACAOS) with interarterial course in adults.

    METHODS AND RESULTS For physiological assessment, fractional flow reserve (FFR) during dobutamine challenge was measured in 37 consecutive adult patients with lone right ACAOS with interarterial course. At baseline, mean FFR was 0.91±0.06, declining to 0.89±0.06 upon dobutamine infusion (p<0.001). Dobutamine stress FFR was significant (≤0.8) in three patients (8.1%), two of whom were surgically treated. Following surgery, dobutamine stress FFR rose from 0.76 to 0.94 and 0.76 to 0.98. Remodelling index (r=0.583, p=0.002), minimal lumen area (diastole: r=0.580, p=0.002; systole: r=0.0618, p<0.001) and per cent area stenosis (r=-0.550, p=0.004), measured by intravascular ultrasound, correlated with dobutamine stress FFR. To assess the clinical relevance, follow-up data of 119 patients with lone right ACAOS with interarterial course were analysed retrospectively. Two deaths occurred during a median follow-up period of 4 years, for a mortality rate of 0.34 per 100 person-year. No instances of myocardial infarction were recorded and one patient did undergo surgical revascularisation in the course follow-up.

    CONCLUSIONS Most instances of lone right ACAOS with interarterial course discovered in adults were physiologically insignificant and ran benign clinical courses. Conservative management may thus suffice in this setting if no definitive signs of myocardial ischaemia are evident.

    PubMed IF 4.4 순환기내과
19. 192016

    제1저자 김지원 · 교신저자 민아름, 이경훈

    Kim JW, Kim DK, Min A, Lee KH, Nam HJ, Kim JH, Kim JS, Kim TY, Im SA, Park IA

    Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2-positive breast cancer.

    J Cancer Res Clin Oncol. 2016;142(1):157-65.

    Abstract

    PURPOSE Human epidermal growth factor receptor 2 (HER2) heterodimerizes and shares common signaling pathways with epidermal growth factor receptor (EGFR). In this study, we investigated the clinical implication of amphiregulin, a ligand for EGFR, on trastuzumab therapy in HER2-positive breast cancer.

    METHODS Serum amphiregulin levels were quantified in 50 consecutive patients with HER2-positive metastatic breast cancer who received first-line trastuzumab plus taxane chemotherapy between October 2004 and July 2009. In addition, in vitro experiments were carried out to validate the results.

    RESULTS The median serum amphiregulin level was 1.0 ng/mL with a maximum level of 4.4 ng/mL. Patients with high serum amphiregulin levels (≥0.5 ng/mL) had significantly shorter progression-free survival (15.1 months vs. not reached; P = 0.018). Colony-forming assays demonstrated that the addition of amphiregulin resulted in increased proliferation of cells. In addition, the anti-proliferative effect of trastuzumab was decreased in the presence of amphiregulin. Western blot analysis showed that amphiregulin activated AKT and ERK pathways. In addition, in the presence of amphiregulin, sustained phosphorylation of AKT and ERK pathways was observed after trastuzumab treatment.

    CONCLUSIONS High serum amphiregulin levels were associated with early disease progression in these patients, possibly due to AKT and ERK signaling activation by amphiregulin.

    PubMed IF 3.3 혈액종양내과
20. 182016

    제1저자 김진원, 남경한 · 교신저자 이근욱

    Kim JW, Nam KH, Ahn SH, Park DJ, Kim HH, Kim SH, Chang H, Lee JO, Kim YJ, Lee HS, Kim JH, Bang SM, Lee JS, Lee KW

    Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer.

    Gastric Cancer. 2016;19(1):42-52.

    Abstract

    BACKGROUND There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC).

    METHODS In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis.

    RESULTS Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7% of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9%; 5-year OS rate, 83.0 vs. 69.1% (P values <0.05)]. Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells [5-year DFS rate, 80.9 vs. 67.0%; 5-year OS rate, 82.5 vs. 68.0% (P values <0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.

    CONCLUSIONS GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.

    PubMed IF 6.1 혈액종양내과
21. 172016

    제1저자 최가람, 오태정 · 교신저자 조영민, 김성완

    Choi K, Lee JC, Oh TJ, Kim M, Kim HC, Cho YM, Kim S

    A Computational Method to Determine Glucose Infusion Rates for Isoglycemic Intravenous Glucose Infusion Study.

    IEEE J Biomed Health Inform. 2016;20(1):4-10.

    Abstract

    The results of the isoglycemic intravenous glucose infusion (IIGI) study need to mimic the dynamic glucose profiles during the oral glucose tolerance test (OGTT) to accurately calculate the incretin effect. The glucose infusion rates during IIGI studies have historically been determined by experienced research personnel using the manual ad-hoc method. In this study, a computational method was developed to automatically determine the infusion rates for IIGI study based on a glucose-dynamics model. To evaluate the computational method, 18 subjects with normal glucose tolerance underwent a 75 g OGTT. One-week later, Group 1 (n = 9) and Group 2 (n = 9) underwent IIGI studies using the ad-hoc method and the computational method, respectively. Both methods were evaluated using correlation coefficient, mean absolute relative difference (MARD), and root mean square error (RMSE) between the glucose profiles from the OGTT and the IIGI study. The computational method exhibited significantly higher correlation (0.95 ± 0.03 versus 0.86 ± 0.10, P = 0.019), lower MARD (8.72 ± 1.83% versus 13.11 ± 3.66%, P = 0.002), and lower RMSE (10.33 ± 1.99 mg/dL versus 16.84 ± 4.43 mg/dL, P = 0.002) than the ad-hoc method. The computational method can facilitate IIGI study, and enhance its accuracy and stability. Using this computational method, a high-quality IIGI study can be accomplished without the need for experienced personnel.

    PubMed IF 7.7 내분비대사내과
22. 162016

    제1저자 구호석 · 교신저자 진호준

    Koo HS, Kim S, Chin HJ

    Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

    Lupus. 2016;25(1):3-11.

    Abstract

    Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission.

    PubMed IF 1.8 신장내과
23. 152016

    제1저자 최지민 · 교신저자 김상균

    Choi JM, Kim SG, Yang HJ, Lim JH, Choi J, Im JP, Kim JS, Kim WH, Jung HC

    Endoscopic predictors for undifferentiated histology in differentiated gastric neoplasms prior to endoscopic resection.

    Surg Endosc. 2016;30(1):89-98.

    Abstract

    BACKGROUND There is often a discrepancy between results from endoscopic forceps biopsy and resected specimen. We aimed to identify endoscopic predictors for undifferentiated histology in differentiated gastric neoplasms prior to endoscopic resection.

    METHODS Medical records of the patients who underwent endoscopic submucosal dissection (ESD) for biopsy-proven differentiated gastric neoplasms at Seoul National University Hospital between July 2005 and July 2014 were retrospectively reviewed. The lesions were divided into two groups based on the final histologic result of ESD: differentiated adenocarcinoma (DA group) and undifferentiated histology (UDH group). The discordant rate, clinicopathologic characteristics, and endoscopic factors were analyzed.

    RESULTS A total of 1641 early gastric cancers from 1615 patients were included. Of these, 1556 (94.8%) were diagnosed as DA and 85 (5.2%) as UDH. The mean age was significantly lower, and number of women was higher in the UDH group than in the DA group. On multivariate analysis, age <65 years [odds ratio (OR) 1.75, 95 % confidence interval (CI) 1.10-2.80], female sex (OR 3.19, 95% CI 2.00-5.08), endoscopic size >10 mm (OR 1.81, 95% CI 1.12-2.92), depressed type (OR 2.85, 95% CI 1.56-5.21), nodularity (OR 2.83, 95% CI 1.59-5.05), and whitish discoloration (OR 19.64, 95% CI 6.98-55.25) were independent predictors.

    CONCLUSIONS Female sex, age <65 years, large endoscopic size, depressed morphology, surface nodularity, and whitish discoloration were predictors for UDH. Meticulous attention should be paid to the lesions with these endoscopic predictors for determining the risk of UDH prior to endoscopic resection.

    PubMed IF 3.3 소화기내과
24. 142016

    제1저자 고동진 · 교신저자 이은봉

    Go DJ, Park JK, Kang EH, Kwon HM, Lee YJ, Song YW, Lee EB

    Survival benefit associated with early cyclosporine treatment for dermatomyositis-associated interstitial lung disease.

    Rheumatol Int. 2016;36(1):125-31.

    Abstract

    Interstitial lung disease (ILD) is the most common cause of death in dermatomyositis (DM). Cyclosporine A (CsA) has shown to be effective in DM-associated ILD (DM-ILD). This study aimed to define the optimal time of CsA administration. A total of 47 patients with DM-ILD, who were treated with CsA at Seoul National University Hospital between January 1998 and June 2013, were enrolled. ILD was diagnosed based on typical chest high-resolution computed tomography (HRCT) findings. Patients with early and delayed CsA treatment were compared in regard to the mortality and ILD progression on HRCT. The early (n = 16) and the delayed treatment group (n = 31) did not differ in regard to baseline clinical characteristics including HRCT scores and pulmonary function. Patients with clinically amyopathic DM (CADM) were more common in the early treatment group. The mortality rate was significantly lower in the early treatment group than in the delayed treatment group (p = 0.009). The survival benefit of early CsA treatment remained significant even after adjusting for age, degree of dyspnea, CADM status, and the year of CsA treatment (hazard ratio 0.057, 95 % confidence interval 0.007-0.472). CsA stabilized disease progression on HRCT in the early treatment group (p = 0.738). Delay in CsA treatment is associated with a worse survival in patients with DM-ILD. Early CsA treatment should be considered at DM-ILD diagnosis especially in patients at a higher risk of developing a rapidly progressive ILD.

    PubMed IF 3.5 류마티스내과
25. 132016

    제1저자 온정헌 · 교신저자 박경수,조남하

    Ohn JH, Kwak SH, Cho YM, Lim S, Jang HC, Park KS, Cho NH

    10-year trajectory of β-cell function and insulin sensitivity in the development of type 2 diabetes: a community-based prospective cohort study.

    Lancet Diabetes Endocrinol. 2016;4(1):27-34.

    Abstract

    BACKGROUND The relative contributions of β-cell function and insulin sensitivity in the pathogenesis of type 2 diabetes are not fully understood. We investigated the longitudinal change in β-cell function and insulin sensitivity in the development of diabetes and the role of genetic variants in deterioration of glucose tolerance.

    METHODS We followed up 4106 participants with normal glucose tolerance (NGT) from the Korean Genome and Epidemiology Study with oral glucose tolerance tests every 2 years for 10 years. We estimated pancreatic β-cell function with the 60 min insulinogenic index (IGI60) and insulin sensitivity with the composite (Matsuda) insulin sensitivity index (ISI). We investigated the association of 66 known type 2 diabetes genetic variants with risk of prediabetes or diabetes and impaired β-cell function and insulin sensitivity.

    FINDINGS During 10 years of follow-up, 1093 (27%) of 4106 participants developed prediabetes and 498 (12%) participants developed diabetes. Compared with participants who remained NGT, those who progressed to diabetes had a lower IGI60 (unadjusted data 5·1 μU/mmol [95% CI 0·5-56·1] vs 7·9 μU/mmol [0·5-113·8]; p<0·0001) and lower ISI (unadjusted data 8·2 [2·6-26·0] vs 10·0 [3·2-31·6]; p<0·0001) at baseline. Participants who had NGT at 10 years showed a decrease in ISI (adjusted data 10·1 [9·9-10·3] vs 7·4 [7·3-7·6]; p<0·0001) but a compensatory increase in IGI60 (adjusted data 6·9 μU/mmol [6·5-7·2] vs 11·7 μU/mmol [11·2-12·1]; p<0·0001) compared with baseline. By contrast, participants who developed diabetes showed a decrease in ISI (adjusted data 8·4 [8·0-8·7] vs 3·0 [2·8-3·2]; p<0·0001) but no significant compensatory increase (p=0·95) in IGI60. A genetic variant near the glucokinase gene (rs4607517) was significantly associated with progression to prediabetes or diabetes (hazard ratio 1·27, 1·16-1·38; p=1·70 × 10(-7)).

    INTERPRETATION Decreased β-cell function, which might be determined partly by genetic factors, and impaired β-cell compensation for progressive decline in insulin sensitivity are crucial factors in the deterioration of glucose tolerance.

    FUNDING South Korean Ministry of Health & Welfare.

    PubMed IF 36.3 내분비대사내과
26. 122016

    제1저자 김주혜 · 교신저자 임재준

    Kim J, Kwak N, Lee HY, Kim TS, Kim CK, Han SK, Yim JJ

    Effect of drug resistance on negative conversion of sputum culture in patients with pulmonary tuberculosis.

    Int J Infect Dis. 2016;42:64-68.

    Abstract

    OBJECTIVE Negative conversion of sputum culture is a useful marker for predicting treatment outcome and relapse of pulmonary tuberculosis (TB). The effect of drug resistance on negative conversion of sputum culture with treatment was evaluated in this study.

    METHODS A total of 535 patients with culture-proven pulmonary TB were classified into three groups: drug-susceptible (DS), other drug-resistant (ODR), and multidrug-resistant/extensively drug-resistant (MDR/XDR). Rates of conversion of sputum culture at 4, 8, and 12 weeks were compared.

    RESULTS At 4 weeks of treatment, the conversion rate in the DS group (52.7%) was higher than that in the ODR group (30.8%, p=0.003), but was not different compared with the MDR group (45.7%, p=0.427). At 8 weeks, the conversion rate in the DS group (76.3%) was higher than that in the ODR (63.5%, p=0.042) and MDR groups (60.0%, p=0.031). At 12 weeks, the conversion rate in the DS group (85.9%) tended to be higher than that in the MDR group (74.3%, p=0.062), but was not different from that in the ODR group (84.6%, p=0.796).

    CONCLUSION The pattern of resistance to anti-TB drugs affects culture conversion rates in the early phase of treatment and also prolongs the time to culture conversion.

    PubMed IF 4.6 호흡기내과
27. 112016

    제1저자 김경아 · 교신저자 정숙향

    Kim KA, Ki M, Choi HY, Kim BH, Jang ES, Jeong SH

    Population-based epidemiology of primary biliary cirrhosis in South Korea.

    Aliment Pharmacol Ther. 2016;43(1):154-62.

    Abstract

    BACKGROUND As a rare disease, only a few population-based epidemiology studies of primary biliary cirrhosis (PBC) have been reported.

    AIMS To elucidate the nationwide prevalence, incidence, complications, fatality and direct medical costs of PBC in South Korea.

    METHODS The nationwide Health Insurance Review and Assessment Service claims data and Rare Intractable Disease registration data on PBC, identified with the International Classification of Diseases (ICD) 10 code of K74.3, were obtained from 2009 to 2013. Age- and gender-specific prevalence and incidence rates of PBC were calculated, and data on complications, comorbidities, prescribed drugs, therapeutic procedures and direct medical costs were analysed.

    RESULTS A total of 2824 patients over 20 years old with PBC were identified in 2009-2013 (female-to-male ratio 6.2, median age 57 years old). The average age- and sex-adjusted incidence from 2011 to 2013 was 8.57 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 47.50 per million population. About 10% of patients presented with complications such as ascites (10.3%), variceal bleeding (5.8%) and/or hepatocellular carcinoma (HCC) (1.3%). Liver transplantation was undertaken in 71 patients (2.5%) for 5 years. Case fatality was 2.2% and the transplantation-free survival was 95.4% for 5 years.

    CONCLUSIONS This is the first report on the nationwide epidemiology of primary biliary cirrhosis in South Korea, demonstrating lower incidence and prevalence rates than those of Western countries, but a considerable disease burden, representing at least 10% were complicated with decompensated cirrhosis or hepatocellular carcinoma requiring liver transplantation.

    PubMed IF 6.8 소화기내과
28. 102016

    제1저자 박재용 · 교신저자 김상균

    Park JY, Kim SG, Kim JS, Jung HC

    Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma.

    Dig Liver Dis. 2016;48(1):81-6.

    Abstract

    BACKGROUND The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved.

    AIMS To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up.

    METHODS Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed.

    RESULTS Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%).

    CONCLUSION Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma.

    PubMed IF 4.9 소화기내과
29. 92016

    제1저자 범승훈 · 교신저자 김동완

    Beom SH, Kim DW, Sim SH, Keam B, Park JH, Lee JO, Kim TM, Lee SH, Heo DS

    Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients.

    Cancer Res Treat. 2016;48(1):88-97.

    Abstract

    PURPOSE Interstitial lung disease (ILD) is a serious adverse effect of gefitinib. We examined the incidence and clinical characteristics of drug-induced ILD in Korean non-small cell lung carcinoma patients treated with gefitinib.

    MATERIALS AND METHODS A retrospective cohort study was performed in non-small cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients' medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities.

    RESULTS Among the 1,114 patients evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and 15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib-induced ILD experienced a fatal clinical course that met either the Common Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the multivariate analysis, a lower serum albumin level (≤ 3.0 g/dL) at baseline was significantly associated with the development of gefitinib-induced ILD (odds ratio, 3.91; 95% confidence interval, 1.20 to 12.71).

    CONCLUSION The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for Japanese population. ILD was usually a life-threatening adverse effect of gefitinib, and the development of ILD was significantly associated with a lower baseline serum albumin level.

    PubMed IF 4.2 혈액종양내과
30. 82016

    제1저자 박종선 · 교신저자 이재호

    Park JS, Lee JY, Lee YJ, Kim SJ, Cho YJ, Yoon HI, Lee CT, Song J, Lee JH

    Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome.

    Antimicrob Agents Chemother. 2016;60(1):92-8.

    Abstract

    Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between antituberculosis drug levels in blood and clinical outcome. Serum concentrations of first-line antituberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and was analyzed using high-performance liquid chromatography-tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome. Among 413 patients, the prevalences of low serum concentrations of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) were 59.9%, 27.8%, 12.8%, and 8.7%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% versus 11.0%; P = 0.026) and was more likely to present with drug-resistant strains (17.6% versus 8.8%; P = 0.049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = 0.072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups. Low serum INH may play a role in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.

    PubMed IF 4.2 호흡기내과

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