SCI 발표논문

전체 4,588편

20382016

제1저자 박준빈 · 교신저자 이승표

, , , , , , , , ,
Quantification of Right Ventricular Volume and Function Using Single-Beat Three-Dimensional Echocardiography: A Validation Study with Cardiac Magnetic Resonance.
J Am Soc Echocardiogr. 2016;29(5):392-401.

Abstract
BACKGROUND Because of the unique geometry of the right ventricle, assessment of right ventricular (RV) volume and function is clinically challenging. The aim of this study was to investigate the feasibility of single-beat three-dimensional echocardiography (sb3DE) for RV volume and functional assessment in patients with dilated right ventricles.
METHODS Fifty-two patients with severe tricuspid regurgitation or atrial septal defects were enrolled. Fifty patients underwent sb3DE and cardiac magnetic resonance (CMR) within 24 hours under a euvolemic state, and the results of sb3DE were compared with those of CMR, the reference method. Fifteen normal subjects were also recruited for a broader validation of sb3DE.
RESULTS Of the 67 individuals, data from 59 study participants (44 patients and 15 normal subjects) with adequate image quality were analyzed (mean age, 46.9 ± 19.3 years; 58% women). The correlation was excellent between sb3DE and CMR for measuring RV volumes and RV ejection fraction (RVEF) (r = 0.96, r = 0.93, and r = 0.93 [P < .001 for all] for RV end-diastolic volume, RV end-systolic volume, and RVEF, respectively). Bland-Altman analysis revealed that RV volumes, but not RVEF, tended to be slightly underestimated by sb3DE (-5.8 ± 9.6%, -3.8 ± 14.1%, and -1.2 ± 9.4% for RV end-diastolic volume, RV end-systolic volume, and RVEF, respectively). Intra- and interobserver variability was acceptable for all indices (4.9% and 6.1% for RV end-diastolic volume, 4.2% and 7.9% for RV end-systolic volume, and 5.7% and 2.8% for RVEF, respectively). Among patients with RV dilation, the difference in RVEF between sb3DE and CMR was more pronounced in patients with atrial fibrillation than those in sinus rhythm (-5.9% vs 0.9%, P = .041).
CONCLUSIONS In patients with dilated right ventricles and in normal subjects, assessment of RV volume and systolic function by sb3DE is feasible in terms of accuracy and reproducibility. RV analysis using sb3DE can be performed in patients with atrial fibrillation, with the possibility of RVEF underestimation.
PubMed IF 8.3 순환기내과
20372016

제1저자 안동원, 박영수 · 교신저자 이상협

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Clinical outcome of acute nonvariceal upper gastrointestinal bleeding after hours: the role of urgent endoscopy.
Korean J Intern Med. 2016;31(3):470-8.

Abstract
BACKGROUND/AIMS This study was performed to investigate the clinical role of urgent esophagogastroduodenoscopy (EGD) for acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) performed by experienced endoscopists after hours.
METHODS A retrospective analysis was performed for consecutively collected data of patients with ANVUGIB between January 2009 and December 2010.
RESULTS A total of 158 patients visited the emergency unit for ANVUGIB after hours. Among them, 60 underwent urgent EGD (within 8 hours) and 98 underwent early EGD (8 to 24 hours) by experienced endoscopists. The frequencies of hemodynamic instability, fresh blood aspirate on the nasogastric tube, and high-risk endoscopic findings were significantly higher in the urgent EGD group. Primary hemostasis was achieved in all except two patients. There were nine cases of recurrent bleeding, and 30-day mortality occurred in three patients. There were no significant differences between the two groups in primary hemostasis, recurrent bleeding, and 30-day mortality. In a multiple linear regression analysis, urgent EGD significantly reduced the hospital stay compared with early EGD. In patients with a high clinical Rockall score (more than 3), urgent EGD tended to decrease the hospital stay, although this was not statistically significant (7.7 days vs. 12.0 days, p > 0.05).
CONCLUSIONS Urgent EGD after hours by experienced endoscopists had an excellent endoscopic success rate. However, clinical outcomes were not significantly different between the urgent and early EGD groups.
PubMed IF 2.2 소화기내과
20362016

제1저자 김형준 · 교신저자 이춘택

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Outcome of incidentally detected airway nodules.
Eur Respir J. 2016;47(5):1510-7.

Abstract
Low-dose chest computed tomography (LDCT) screening increased detection of airway nodules. Most nodules appear to be secretions, but pathological lesions may show similar findings. The National Comprehensive Cancer Network (NCCN) recommends repeating LDCT after 1 month and proceeding to bronchoscopy if the nodules persist. However, no reports exist about incidentally detected airway nodules. We investigated the significance of airway nodules detected by LDCT screening.We screened patients with incidental airway nodules detected by LDCT in the Seoul National University Hospital group. The characteristics of computed tomography, bronchoscopy, pathology and clinical findings were analysed.Among 53 036 individuals who underwent LDCT screening, 313 (0.6%) had airway nodules. Of these, 186 (59.4%) were followed-up with chest computed tomography and/or bronchoscopy. Seven (3.8%) cases had significant lesions, including leiomyoma (n=2), endobronchial tuberculosis (n=2), chronic inflammation (n=1), hamartoma (n=1) and benign granuloma (n=1). The remaining 179 lesions were transient, suggesting that they were secretions.The use of LDCT for lung cancer screening demonstrated the low incidence of airway lesions. Most lesions were transient secretions. True pathological lesions were rare, and no malignant lesion was found. The current recommendation of the NCCN guideline is a reasonable approach that can avoid unnecessary bronchoscopy.
PubMed IF 23.8 호흡기내과
20352016

제1저자 이민호, 박진주 · 교신저자 윤창환, 채인호

, , , , , , , , , , , , , , ,
Impact of smoking status on clinical outcomes after successful chronic total occlusion intervention: Korean national registry of CTO intervention.
Catheter Cardiovasc Interv. 2016;87(6):1050-62.

Abstract
OBJECTIVES We sought to evaluate the effect of cigarette smoking on long-term outcomes after successful percutaneous coronary intervention for chronic total occlusion (CTO) lesions.
BACKGROUND Cigarette smoking promotes the progression of atherosclerosis but enhances the antiplatelet effect of clopidogrel.
METHODS The Korea National Registry of CTO Intervention included 2,167 patients with CTO lesions from 26 centers who were successfully revascularized with drug-eluting stents from 2007 to 2009. Thrombotic events were defined as the composite of cardiac death, nonfatal myocardial infarction, and stent thrombosis.
RESULTS Current-smokers had more favorable baseline characteristics such as a younger age and lower prevalence of hypertension and diabetes mellitus. At 1 year, current-smokers had a significantly lower thrombotic event rate (1.1% vs. 2.7%, P = 0.034), but a significantly higher target vessel revascularization (TVR) rate (7.2% vs. 4.2%, P = 0.017) compared with never-smokers. After adjustment, current-smoking was independently associated with a 72% decreased risk for thrombotic events, and 73% increased risk for TVR.
CONCLUSIONS In patients with a revascularized CTO lesion, cigarette smoking is associated with fewer thrombotic events but with a higher incidence of TVR. Patients with CTO may benefit from smoking cessation to reduce TVR in conjunction with the use of new more potent antiplatelet agents whose effect is independent of cigarette smoking to improve thrombotic events. © 2015 Wiley Periodicals, Inc.
PubMed IF 1.9 순환기내과
20342016

제1저자 최윤진 · 교신저자 김나영

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Familial Clustering of Gastric Cancer: A Retrospective Study Based on the Number of First-Degree Relatives.
Medicine (Baltimore). 2016;95(20):e3606.

Abstract
This comprehensive cross-sectional study aimed to identify factors contributing to familial aggregation of gastric cancer (GC). A total of 1058 GC patients and 1268 controls were analyzed separately according to the presence or absence of a first-degree relative of GC (GC-relative). Logistic regression analysis adjusted for age, gender, residence during childhood, smoking, alcohol intake, monthly income, spicy food ingestion, Helicobacter pylori status and host cytokine polymorphisms was performed. Cytotoxin-associated gene A (cagA) positivity was a distinctive risk factor for GC in the family history (FH)-positive group (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.42-4.00), while current/ex-smoker, moderate to strong spicy food ingestion, and non-B blood types were more closely associated with GC in the FH-negative group. Among the FH-positive group, alcohol consumption showed a synergistic carcinogenic effect in the at least 2 GC-relatives group compared to the 1 GC-relative group (1.71 vs. 9.58, P for interaction = 0.026), and this was dose-dependent. In the subjects with ≥2 GC-relatives, TGFB1-509T/T was a risk factor for GC (OR 23.74; 95% CI 1.37-410.91), as were rural residency in childhood, alcohol consumption, spicy food ingestion, and cagA positivity. These results suggest that subjects with FH may be a heterogeneous group in terms of gastric cancer susceptibility. Especially, subjects with ≥2 GC-relatives should undergo risk stratification including TGFB1-509T/T and alcohol consumption.
PubMed IF 2 소화기내과
20332016

제1저자 최윤진 · 교신저자 김나영

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Upregulation of Vanilloid Receptor-1 in Functional Dyspepsia With or Without Helicobacter pylori Infection.
Medicine (Baltimore). 2016;95(19):e3410.

Abstract
The etiological basis of functional dyspepsia (FD) is incompletely understood. The aim of this study was to evaluate the involvement of nociceptor-related genes and Helicobacter pylori (HP) in the pathogenesis of FD. The expression of nociceptor-related genes was measured in gastric cell lines that were co-cultured with HP. FD patients (n = 117) and controls (n = 55) were enrolled from a tertiary hospital gastroenterology clinic. Expression of the genes nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the gastric mucosa were detected by reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemical staining of TRPV1 was analyzed. These measurements were repeated after 1 year. TRPV1, GDNF, and NGF expression was elevated in gastric cell lines co-cultured with HP. TRPV1 immunostaining was stronger in HP-positive than HP-negative subjects. The FD group showed higher expression levels of TRPV1, GDNF, and NGF and increased TRPV1 immunostaining compared with those of the control group (all P < 0.05). Among 61 subjects who were followed up at 1 year, controls with successful HP eradication and patients whose symptoms had improved both showed significant reductions in the expression of TRPV1 and NGF (all P < 0.05) compared with controls without HP eradication and patients whose symptoms had not improved, respectively. The expression of NGF, GDNF, and TRPV1 may be associated with the pathogenesis of FD. Since HP infection may induce the increased expression of these genes, anti-HP therapy could be beneficial for HP-positive patients with FD.
PubMed IF 2 소화기내과
20322016

제1저자 이정환 · 교신저자 임춘수

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Factors Affecting the Referral Time to Nephrologists in Patients With Chronic Kidney Disease: A Prospective Cohort Study in Korea.
Medicine (Baltimore). 2016;95(19):e3648.

Abstract
Timely referral to nephrologists is important for improving clinical outcomes and reducing costs during transition periods. We evaluated the impact of patients' demographic, clinical, and social health characteristics on referral time.A total of 1744 CKD patients who started maintaining dialysis were enrolled in a Korean prospective cohort. The early referral (ER) and late referral group (LR) were defined as patients who were referred to a nephrologist more than or less than 1 year prior to dialysis initiation, respectively.A total of 1088 patients (62.3%) were in the ER, and 656 patients (37.6%) were in the LR. Among the patients in the LR, 398 patients (60.7%) were referred within the 3 months prior to the start of dialysis (ultralate referral group [ULR]). The ER was younger at the time of referral than the LR; however, the ER was older at the start of dialysis. Patients with diabetes or hypertension as the cause of kidney disease were more common in the LR, whereas patients with glomerulonephritis, females, and nonsmokers were more common in the ER. The ER had more well-controlled blood pressure, lower phosphorus levels, and higher hemoglobin levels at the start of dialysis. Congestive heart failure (CHF) was more common in the LR. In the multivariate analysis, male sex (odds ratio [OR] 1.465, 95% confidence interval [CI] 1.034-2.076), underlying kidney disease (diabetes mellitus [OR 1.507, 95% CI 1.057-2.148] and hypertension [OR 1.995, 95% CI 1.305-3.051]), occupation (mechanician [OR 2.975, 95% CI 1.445-6.125], laborer [OR 3.209, 95% CI 1.405-7.327], and farmer [OR 5.147, 95% CI 2.217-11.953]), CHF (OR 2.152, 95% CI 1.543-3.000), and ambulatory status (assisted-walks, OR 2.072, 95% CI 1.381-3.111) were proved as the independent risk factor for late referral.Patients with hypertensive or diabetic kidney disease are referred later than those with glomerulonephritis. Male patients with physically active occupations exhibiting CHF and restricted ambulation were associated with a late referral. Considering the various factors associated with late referral, efforts to increase early referrals should be emphasized, particularly in patients with hypertension, diabetes, or congestive heart failure.
PubMed IF 2 신장내과
20312016

제1저자 이정환 · 교신저자 이정표

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Pretransplant Hepatitis B Viral Infection Increases Risk of Death After Kidney Transplantation: A Multicenter Cohort Study in Korea.
Medicine (Baltimore). 2016;95(21):e3671.

Abstract
Clinical outcomes in kidney transplant recipients (KTRs) with hepatitis B virus (HBV) have not been thoroughly evaluated. Here, we investigated recent posttransplant clinical outcomes of KTRs with HBV and compared them with KTRs with hepatitis C virus (HCV) and seronegative KTRs.Of 3855 KTRs from April 1999 to December 2011, we enrolled 3482 KTRs who had viral hepatitis serology data; the patients were followed up for 89.1 ± 54.1 months. The numbers of recipients with HBV and HCV were 160 (4.6%) and 55 (1.6%), respectively. We analyzed the clinical outcomes, including overall mortality and graft failure, among patients who had undergone kidney transplantation.Patients with HBV showed poorer survival (P = 0.019; adjusted hazard ratio [HR] = 2.370; 95% confidence interval [CI]: 1.155-4.865) than KTRs without HBV. However, the graft survival of patients with chronic hepatitis B did not differ from that of patients without HBV. Hepatic complications were the primary causes of mortality of KTRs with HBV. Mortality significantly correlated with a higher grade of inflammation (P = 0.002) and with the use of lamivudine or adefovir antiviral treatment (P = 0.016). HBV-positive KTRs treated with the new-generation antiviral agent entecavir showed improved patient survival compared with KTRs receiving lamivudine (log-rank P = 0.050). HCV did not affect patient survival; however, it increased the incidence of graft failure (P = 0.010; adjusted HR = 2.899; 95% CI: 1.289-6.519). KTRs with HCV had an increased incidence of acute rejection (log-rank P = 0.005, crude HR = 2.144; 95% CI: 1.341-3.426; P = 0.001).KTRs with chronic hepatitis B may exhibit poor survival due to post-transplantation hepatic complications. Pretransplant histological liver evaluations and adequate antiviral management with potent nucleoside/nucleotide analogues are needed to improve the survival of KTRs with chronic hepatitis B even when liver function is within the normal range.
PubMed IF 2 신장내과
20302016

제1저자 이창훈, 김지민 · 교신저자 윤호일

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Inhaled Corticosteroids Use Is Not Associated With an Increased Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus: Two Nested Case-Control Studies.
Medicine (Baltimore). 2016;95(22):e3627.

Abstract
There have been concerns that systemic corticosteroid use is associated with pregnancy-induced hypertension (PIH) and diabetes mellitus. However, the relationship between inhaled corticosteroids (ICSs) and the risk of PIH has not been fully examined, and there was no study investigating the association between ICS use and the development of gestational diabetes mellitus (GDM). The aims of the study are to determine whether the use of ICSs during pregnancy increases the risk of PIH and GDM in women.We conducted 2 nested case-control studies utilizing the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea), in which 1,306,281 pregnant women who delivered between January 1, 2009 and December 31, 2011 were included. Among them, PIH cases and GDM cases were identified and matched controls were included. Conditional logistic regression analyses adjusted by other concomitant drugs use during and before pregnancy and confounding covariates including comorbidities were performed.Total 43,908 PIH cases and 219,534 controls, and 34,190 GDM cases and 170,934 control subjects were identified. When other concomitant drugs use during pregnancy was adjusted, ICS use was associated with an increased rate of PIH (adjusted odds ratio, 1.40 [95% CI, 1.05-1.87]). ICS medication possession ratios and cumulative doses were associated with an increased risk of PIH. However, the statistical significance was not found in other models. In both unadjusted and adjusted multivariable models, ICSs use was not associated with increase in the risk of GDM.ICSs use is not associated with an increased risk of PIH and GDM.
PubMed IF 2 호흡기내과
20292016

제1저자 박진균, 변주연 · 교신저자 이은봉, 이영미

, , , , , , , , , , , ,
HM71224, a novel Bruton's tyrosine kinase inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in a mouse model: a potential drug for rheumatoid arthritis.
Arthritis Res Ther. 2016;18:91.

Abstract
BACKGROUND Bruton's tyrosine kinase (Btk) is critical for activation of B cells and myeloid cells. This study aimed to characterize the effects of HM71224, a novel Btk inhibitor, both in vitro and in a mouse model of experimental arthritis.
METHODS The kinase inhibition profile of HM71224 was analyzed. The in vitro effects of HM71224 on B cells and monocytes were analyzed by examining phosphorylation of Btk and its downstream signaling molecules, along with cytokine production and osteoclast formation. The in vivo effects of HM71224 were investigated in a mouse model of collagen-induced arthritis (CIA).
RESULTS HM71224 irreversibly bound to and inhibited Btk (IC50 = 1.95 nM). The compound also inhibited the phosphorylation of Btk and its downstream molecules such as PLCγ2, in activated Ramos B lymphoma cells and primary human B cells in a dose-dependent manner. Furthermore, HM71224 effectively inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes. Finally, HM71224 improved experimental arthritis and prevented joint destruction in a murine model of CIA.
CONCLUSIONS HM71224 inhibits Btk in B cells and monocytes and ameliorates experimental arthritis in a mouse model. Thus, HM71224 is a potential novel therapeutic agent for rheumatoid arthritis in humans.
PubMed IF 5.4 류마티스내과
20282016

제1저자 현민경 · 교신저자 이창훈

, , , ,
Effect of inhaled drugs on anxiety and depression in patients with chronic obstructive pulmonary disease: a prospective observational study.
Int J Chron Obstruct Pulmon Dis. 2016;11:747-54.

Abstract
OBJECTIVE We investigated the effect of treatment with inhaled drugs on changes in mood, focusing on depression and anxiety during treatment in patients with newly diagnosed chronic obstructive pulmonary disease (COPD).
METHODS We prospectively selected new COPD patients from three Seoul National Hospitals. Participants underwent face-to-face interviews to evaluate clinical characteristics and drug use, and completed questionnaires using the Hospital Anxiety and Depression Scale (HADS) at the start of the project, the 4th week, and the 12th week. We compared changes in HADS scores both between inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) users and non-ICS/LABA users, as well as between long-acting muscarinic antagonist (LAMA) users and non-LAMA users. The general linear mixed model was applied for multivariate analysis.
RESULTS Ninety new COPD patients participated in the study. Of these 90 patients, 84 completed face-to-face interviews. In the univariate analysis, those who were treated by ICS/LABA or LAMA showed a significant increase in HADS-A at the 4-week evaluation (0.73±2.56, P=0.038), but the statistical significance was lost in the multivariable analysis. No significant difference was found in the change in HADS scores between ICS/LABA users and non-ICS/LABA users, or between LAMA users and non-LAMA users in multivariate general linear mixed model analyses.
CONCLUSION In this prospective observational study, we found no significant effects of inhaled treatment on mood problems among new COPD patients. Further research should be conducted to identify the association between anxiety and depression and inhaled drugs for COPD treatment.
PubMed IF 4.1 호흡기내과
20272016

제1저자 허진 · 교신저자 김효수

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CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages.
Cell Stem Cell. 2016;18(4):508-21.

Abstract
Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82(-/-) mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-β1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC(+) BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche.
PubMed IF 23.3 순환기내과
20262016

제1저자 구보경 · 교신저자 이창훈

, , , ,
Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study.
PLoS One. 2016;11(4):e0153107.

Abstract
AIMS/INTRODUCTION This study aimed to estimate the prevalence of gestational diabetes mellitus (GDM) and use of anti-diabetic medications for patients with GDM in Korea, using data of the period 2007-2011 from the Health Insurance Review and Assessment (HIRA) database, which includes the claims data of 97% of the Korean population.
MATERIALS AND METHODS We used the Healthcare Common Procedure Coding System codes provided by the HIRA to identify women with delivery in the HIRA database between 2009 and 2011. GDM was defined according to ICD-10 codes, and patients with pre-existing diabetes between January 1, 2007 and pregnancy were excluded. A Poisson regression was performed to evaluate the trends in annual prevalence rates.
RESULTS The annual numbers of deliveries in 2009-2011 were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM during that period was 7.5% in 2009-2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in 2011. The age-stratified analysis showed that the prevalence of GDM was highest in women aged 40-44 years, at 10.6% in 2009-2011, and that the annual prevalence significantly increased even in young women aged 20-29 years during that period (P < 0.05). More than 95% of the patients with GDM did not take any anti-diabetic medication. Among the anti-diabetic medications prescribed for patients with GDM, insulin was most commonly prescribed (for >98% of the patients with GDM on medication).
CONCLUSIONS The prevalence of GDM in Korean women recently reached 5.7-9.5% in recent years. This represents a public health concern that warrants proper screening and medical care for GDM in women during the childbearing years.
PubMed IF 2.8 호흡기내과
20252016

제1저자 김동완 · 교신저자 Shaw AT

, , , , , , , , , , , , , , , , , , , ,
Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial.
Lancet Oncol. 2016;17(4):452-463.

Abstract
BACKGROUND ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK-rearranged NSCLC.
METHODS ASCEND-1 was an open-label, phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe, North America, and Asia-Pacific. Eligible patients were aged 18 years or older with ALK-rearranged locally advanced or metastatic cancer that had progressed despite standard therapy (or for which no effective standard therapy existed), who had at least one measurable lesion at baseline. The primary objective (to determine the maximum tolerated dose) has been reported previously. This updated analysis includes all patients with ALK-rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/day in the dose-escalation and expansion phases. Here we report the secondary outcomes of overall response, duration of response, and progression-free survival, analysed in all patients who received at least one 750 mg dose of ceritinib. Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists, in patients with untreated or locally treated neurologically stable brain metastases at baseline. Safety was assessed in all patients who received at least one dose of ceritinib. This study is no longer recruiting patients; however, treatment and follow-up are ongoing. This study is registered with ClinicalTrials.gov, number NCT01283516.
FINDINGS Between Jan 24, 2011, and July 31, 2013, 255 patients were enrolled and received at least one dose of ceritinib 750 mg/day, of whom 246 had ALK-rearranged NSCLC. At data cutoff (April 14, 2014), median follow-up was 11·1 months (IQR 6·7-15·2) and 147 (60%) patients had discontinued treatment, 98 (40%) as a result of disease progression. An overall response was reported in 60 (72% [95% CI 61-82]) of 83 ALK inhibitor-naive patients and 92 (56% [49-64]) of 163 ALK inhibitor-pretreated patients. Median duration of response was 17·0 months (95% CI 11·3-non-estimable [NE]) in ALK inhibitor-naive patients and 8·3 months (6·8-9·7) in ALK inhibitor-pretreated patients. Median progression-free survival was 18·4 months (95% CI 11·1-NE) in ALK inhibitor-naive patients and 6·9 months (5·6-8·7) in ALK inhibitor-pretreated patients. Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment, intracranial disease control was reported in 15 (79% [95% CI 54-94]) of 19 ALK inhibitor-naive patients and in 49 (65% [54-76]) of 75 ALK inhibitor-pretreated patients. Of these 94 patients, 11 had measurable brain lesions and no previous radiotherapy to the brain, six of whom achieved a partial intracranial response. Serious adverse events were recorded in 117 (48%) of 246 patients. The most common grade 3-4 laboratory abnormalities were increased alanine aminotransferase (73 [30%] patients) and increased aspartate aminotransferase (25 [10%]). The most common grade 3-4 non-laboratory adverse events were diarrhoea and nausea, both of which occurred in 15 (6%) patients. Two on-treatment deaths during the study were deemed to be related to study drug by the investigators, one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis.
INTERPRETATION The durable whole-body responses reported, together with the intracranial activity, support a clinical benefit for treatment with ceritinib in patients with ALK-rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib. A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK-rearranged NSCLC and brain or leptomeningeal metastases.
FUNDING Novartis Pharmaceuticals Corporation.
PubMed IF 33.7 혈액종양내과
20242016

제1저자 박성열, 남수정 · 교신저자 김범석

, , , , , , , , , , ,
VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.
Cancer Res Treat. 2016;48(2):518-26.

Abstract
PURPOSE The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC).
MATERIALS AND METHODS A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS).
RESULTS In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS.
CONCLUSION High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.
PubMed IF 4.2 혈액종양내과
20232016

제1저자 옥찬영 · 교신저자 김범석

, , , , , , , , , , , , , , , ,
Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma.
J Cancer Res Clin Oncol. 2016;142(4):873-83.

Abstract
PURPOSE We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response.
METHODS Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10 %.
RESULTS Of the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2 % of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95 % confidence interval 2.07-20.10, P < 0.001).
CONCLUSIONS Comprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.
PubMed IF 3.3 혈액종양내과
20222016

제1저자 전미성 · 교신저자 김태유

, , , , , ,
Aberrant Epigenetic Modifications of LPHN2 Function as a Potential Cisplatin-Specific Biomarker for Human Gastrointestinal Cancer.
Cancer Res Treat. 2016;48(2):676-86.

Abstract
PURPOSE Epigenetic alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. However, there are currently no standardized epigenetic biomarkers for drug sensitivity in human gastrointestinal cancer. Therefore, the aim of this study is to identify a novel epigenetic biomarker in gastrointestinal cancer.
MATERIALS AND METHODS Using bisulfite sequencing and pyrosequencing analysis, DNA methylation patterns of gastric, colon primary tissues and their cancer cells were analyzed, and histone modifications were analyzed using chromatin immunoprecipitation assay. In addition, cancer cells were exposed to cisplatin and treated with a DNA methyltransferase inhibitor.
RESULTS We report that in human gastric and colon cancers, latrophilin 2 (LPHN2) is silenced by epigenetic modifications, including CpG island methylation and aberrant histone modifications. We also confirmed that LPHN2 was silenced by DNA hypermethylation in primary gastric and colon tumor tissues compared to their normal counterparts. Interestingly, we found that cancer cells with methylated LPHN2 showed higher sensitivity to cisplatin. Also, 5-aza- 2'-deoxycytidine combined with cisplatin decreased the cytotoxicity of cisplatin in cancer cells with methylated LPHN2. In addition, LPHN2 knockdown in cancer cells with high LPHN2 expression sensitized these cells to the anti-proliferative effects of cisplatin.
CONCLUSION In human gastrointestinal cancer, we found that LPHN2 is regulated by epigenetic modifications, and that cancer cells with lower LPHN2 expression show higher sensitivity to cisplatin. Therefore, the methylation status of LPHN2 is a potential novel epigenetic biomarker for cisplatin treatment in human gastric and colon cancers.
PubMed IF 4.2 혈액종양내과
20212016

제1저자 김수환, 김병관 · 교신저자 김원

, , , , , , , ,
Characterization of gastrointestinal hemorrhage and prediction of mortality in Asian patients with alcoholic hepatitis.
J Gastroenterol Hepatol. 2016;31(4):814-21.

Abstract
BACKGROUND AND AIM Gastrointestinal bleeding (GIB) often accompanies alcoholic hepatitis (AH). The study aimed to investigate clinical characteristics of GIB in AH patients and to identify risk factors for mortality in AH patients with GIB.
METHODS Data from 329 patients hospitalized with AH in a single center during 1999-2014 were retrospectively analyzed. Patients with AH were dichotomized into GIB and non-GIB groups. The GIB group was further divided into portal hypertensive bleeding (PHB) and non-PHB groups. Clinical characteristics and survival outcomes were compared between the groups. Risk factors for mortality were analyzed using Cox regression.
RESULTS Among the 329 AH patients, 132 experienced GIB at admission or during hospitalization. The most common cause of GIB was an esophageal varix. The GIB group had worse survival outcomes than the non-GIB group (log-rank test, P = 0.034). The PHB group had worse survival outcomes than the non-PHB group (log-rank test, P = 0.001). On multivariate analysis, alcohol consumption, ascites, encephalopathy, infection, Maddrey's discriminant function, and the model for end-stage liver disease (MELD) score independently predicted mortality in the entire AH cohort. The MELD score (hazard ratio, 1.085; 95% confidence interval, 1.052-1.120; P < 0.001) and PHB (hazard ratio, 2.162; 95% confidence interval, 1.021-4.577; P = 0.044) were significant prognosticators for patients with AH and GIB.
CONCLUSIONS The presence of PHB and a higher MELD score adversely affected survival in AH patients with GIB. Accordingly, prompt endoscopic examination for exploring the etiologies of GIB may alert physicians to predict the risk of death in AH patients with GIB.
PubMed IF 3.5 소화기내과
20202016

제1저자 옥찬영 · 교신저자 오도연

, , , , , , ,
Metabolic landscape of advanced gastric cancer according to HER2 and its prognostic implications.
Gastric Cancer. 2016;19(2):421-430.

Abstract
BACKGROUND In advanced gastric cancer (AGC), HER2 is a validated therapeutic target. However, the metabolic landscape of AGC based on HER2 status has not been reported. Furthermore, the prognostic value of HER2 in AGC is under debate. The purpose of this study was to determine the metabolic landscape and prognosis on the basis of HER2 status in AGC.
METHODS We analyzed 866 AGC patients treated with palliative chemotherapy and whose HER2 status was evaluated. HER2 positivity was defined as HER2 IHC 3+ or HER2/CEP17 ratio ≥2. Among them, 363 patients were evaluated with (18)F FDG-PET before chemotherapy. We analyzed mSUV (maximal standardized uptake value) according to HER2 status and clinical outcomes.
RESULTS Among 866 patients, 225 (26.0 %) had HER2+ GC. The mSUV of HER2+ GC was significantly higher than that of HER2- GC (12.6 vs. 8.7, p < 0.001). Increased HER2 IHC positivity was correlated with increased mSUV (IHC-: 8.1, IHC 1+: 8.2, 2+: 11.4, 3+: 13.2, p < 0.001). Excluding HER2+ patients who received HER2-targeting agents, OS of patients was not different by HER2 status (12.5 vs. 11.9 months, p = 0.688). However, according to tumor metabolism, patients with higher mSUV showed worse OS regardless of HER2 positivity (mSUV < 12.8:14.8, ≥12.8:8.6 months, p < 0.001).
CONCLUSION Tumor metabolism of AGC adversely influenced OS under treatment with cytotoxic chemotherapy. Tumor metabolism was higher in HER2+ AGC than HER2-. However, HER2 was not a prognostic factor in patients who received chemotherapy without HER2-targeting agents.
PubMed IF 6.1 혈액종양내과
20192016

제1저자 옥찬영 · 교신저자 오도연

, , , , , , , ,
Weight loss at the first month of palliative chemotherapy predicts survival outcomes in patients with advanced gastric cancer.
Gastric Cancer. 2016;19(2):597-606.

Abstract
BACKGROUND Weight loss during chemotherapy is a significant prognostic factor for poor survival in patients with advanced gastric cancer (AGC). However, in most studies, weight loss was measured at the end of chemotherapy, limiting its clinical use. In this study, we evaluated whether weight loss during the first month of chemotherapy could predict survival outcomes in patients with AGC.
METHODS We analyzed 719 patients with metastatic or recurrent AGC who were receiving palliative chemotherapy. We calculated the initial body mass index (BMIi), percent weight loss after 1 month of chemotherapy (ΔW 1m), percent weight loss after last administration of chemotherapy (ΔW end), and average weight loss per month during chemotherapy (ΔW/m). We correlated these data with overall survival (OS) by receiver-operating characteristic (ROC) curves and Kaplan-Meier curves, and performed a subgroup analysis using Cox regression.
RESULTS The probabilities of longer OS had stronger correlations with ΔW/m and ΔW 1m than with ΔW end or BMIi. A significant positive correlation between ΔW 1m and ΔW/m (r (2) = 0.591, p < 0.001) was observed. Median OS of patients with ΔW 1m more than 3 % was significantly shorter than in patients with less weight loss (OS: 9.7 vs. 16.3 months, p < 0.001). Subgroup analysis revealed that ΔW 1m accompanied poor survival irrespective of other clinical characteristics.
CONCLUSION Weight loss at the very first month of palliative chemotherapy could predict unfavorable survival outcomes in AGC.
PubMed IF 6.1 혈액종양내과
20182016

제1저자 손일석 · 교신저자 오병희

, , , , , , ,
Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial.
Am J Cardiovasc Drugs. 2016;16(2):129-38.

Abstract
BACKGROUND This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).
METHODS In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.
RESULTS A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were -9.50 (8.46) mmHg in the OM/AML/HCTZ group and -4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.
CONCLUSION In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).
PubMed IF 3.2 순환기내과
20172016

제1저자 이기형 · 교신저자 오도연, 임석아

, , , , , , , , , , , , , , , , ,
A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.
Support Care Cancer. 2016;24(4):1709-17.

Abstract
PURPOSE Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim.
METHODS In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1.
RESULTS The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly.
CONCLUSIONS Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.
PubMed IF 3.4 혈액종양내과
20162016

제1저자 김경임 · 교신저자 윤성수, 오정미

, , , , , , , , , ,
Psychometric analysis of the Korean version of the high-dose chemotherapy specific quality of life questionnaire module from the European Organization for Research and Treatment of Cancer (EORTC QLQ-HDC29).
Qual Life Res. 2016;25(4):881-90.

Abstract
PURPOSE We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer high-dose chemotherapy specific quality of life questionnaire module (EORTC QLQ-HDC29) when implemented with Korean patients by conducting a multicenter, longitudinal study in three Korean hospitals.
METHODS A total of 226 patients who scheduled to receive the HDC followed by hematopoietic stem cell transplantation (HSCT) were enrolled. The patients were asked to complete three questionnaires [the EORTC Core Questionnaire (QLQ-C30), QLQ-HDC29, and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation] at four points in time: before HSCT and 100, 180, and 365 days after HSCT. Standard validity and reliability analyses were performed.
RESULTS Internal consistency of the QLQ-HDC29 was generally acceptable, as tested by Cronbach's α, except for the scales body image and the inpatient issues. Cronbach's α values for the Korean version of the QLQ-HDC29 were almost in accordance with results of the original version, except for the scales body image (lower to the original QLQ-HDC29, α = 0.73) and impact on family (higher to the original QLQ-HDC29, α = 0.52). Known-group comparison analyses showed significantly higher symptom burdens in patients with poor performance status or graft versus host disease (similar to the original QLQ-HDC29). The QLQ-HDC29 indicated good convergent and discriminant validity and showed responsiveness to changes in line with a clinical course over time after HSCT.
CONCLUSIONS The QLQ-HDC29 is generally reliable and adequate to assess QoL in Korean patients undergoing HDC followed by HSCT.
PubMed IF 3.4 혈액종양내과
20152016

제1저자 진은효 · 교신저자 김상균

, , , , ,
Clinical outcomes of re-stenting in patients with stent malfunction in malignant gastric outlet obstruction.
Surg Endosc. 2016;30(4):1372-9.

Abstract
BACKGROUND AND AIMS Self-expanding metal stents (SEMS) have been used for the palliative treatment of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the clinical outcomes of salvage SEMS for stent malfunction and to identify the prognostic factors for a longer patency.
METHODS A total of 108 patients who underwent a secondary salvage SEMS placement for a primary stent malfunction were retrospectively reviewed at the Seoul National University Hospital between August 2004 and May 2013. The duration of patency for salvage SEMS was defined as the time between salvage SEMS placement and the recurrence of obstructive symptoms that were confirmed either endoscopically or radiologically.
RESULTS The technical and clinical success rates for salvage SEMS were 100 and 82.4% (95% confidence interval [CI] 74.0-89.0), respectively. A salvage SEMS malfunction occurred in 29 (26.9%) of the 108 patients. The median duration of patency for salvage SEMS was 59.5 days (range 3-928, 95% CI 73.7-118.3). Longer SEMS patencies of more than 60 days were significantly associated with palliative chemotherapy (odds ratio = 2.539, 95% CI 1.031-6.252, p = .043). For salvage SEMS, covered-uncovered stents had a longer patency duration, as compared with other combinations of primary and salvage stent types.
CONCLUSIONS Longer patency durations for salvage SEMS were associated with palliative chemotherapy after salvage SEMS insertion. Salvage SEMS could be a feasible and effective treatment for primary stent malfunction in malignant GOO.
PubMed IF 3.3 소화기내과
20142016

제1저자 김세중 · 교신저자 이춘택

, , , , , , , , , ,
Factors associated with preserved pulmonary function in non-small-cell lung cancer patients after video-assisted thoracic surgery.
Eur J Cardiothorac Surg. 2016;49(4):1084-90.

Abstract
OBJECTIVES Some non-small-cell lung cancer patients have preserved pulmonary function after surgery. Compared with open thoracotomy, video-assisted thoracic surgery (VATS) is widely performed and preserves pulmonary function. Patients with non-small-cell lung cancer have an extremely poor prognosis without surgery. Clinicians should therefore decide which patients can safely tolerate lung resection. This study aimed to identify factors associated with preserving pulmonary function after VATS in non-small-cell lung cancer patients.
METHODS Three hundred and fifty-one patients with non-small-cell lung cancer underwent VATS and preoperative and 12-month postoperative pulmonary function tests. Patients with and patients without preserved forced expiratory volume in 1 s (FEV1) and diffusing capacity of carbon monoxide were compared.
RESULTS The FEV1 was preserved after VATS in 142 (40.5%) patients. In multivariable analysis, this group was significantly associated with VATS sublobar resection (P < 0.001) and resection at the right upper lobe or right middle lobe (vs right lower lobe, P = 0.048; vs left upper lobe, P = 0.003; vs left lower lobe, P = 0.015). Diffusing capacity of carbon monoxide was preserved in 129 (36.8%) patients. Multivariable analysis showed that VATS sublobar resection (P < .001), lower baseline diffusing capacity of carbon monoxide (P < 0.001) and right upper lobe or right middle lobe resection (vs right lower lobe, P = 0.0014; vs left upper lobe, P = 0.029, vs left lower lobe, P = 0.014) were significantly associated with preserved diffusing capacity of carbon monoxide.
CONCLUSIONS For preserving pulmonary function after non-small-cell lung cancer surgery, VATS sublobar resection was superior to VATS lobectomy, and surgery on the right upper lobe or right middle lobe was superior to that at other sites.
PubMed IF 3.3 호흡기내과
20132016

제1저자 신철민 · 교신저자 김나영

, , , , ,
Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication.
Dig Dis Sci. 2016;61(4):1051-9.

Abstract
BACKGROUND Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet.
AIMS To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM).
METHODS Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up.
RESULTS Average follow-up duration was 33.7 months (range 2-97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (ρ = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015).
CONCLUSIONS In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression.
PubMed IF 2.8 소화기내과
20122016

제1저자 김병근 · 교신저자 강혜련

, , , , , , ,
Allergies are still on the rise? A 6-year nationwide population-based study in Korea.
Allergol Int. 2016;65(2):186-191.

Abstract
BACKGROUND Some western countries recently have shown a slowdown in the incidence of allergic diseases after worldwide increasing trends, but there are few data from Asian populations concerning changing trend of allergic diseases. We evaluated the recent trends in the prevalence of asthma and other allergic diseases in Korea.
METHODS From the database of Korean National Health Insurance, a nationwide diagnostic data from 2009 to 2014 were extracted and the national prevalence was analyzed.
RESULTS The prevalence per 1000 people of atopic dermatitis, allergic rhinitis, and asthma in 2014 was 19.0, 133.1, and 36.3, respectively. The prevalence of three diseases was highest in the age group under 10 as, 95.0, 384.1, and 132.1 per 1000 people, while the prevalence in the over-10-year-group was only 11.6, 109.5, and 27.3, respectively. The prevalence of atopic dermatitis and allergic rhinitis gradually decreased with older age, but the prevalence of asthma showed a re-increasing pattern from the age group 30-39 and reached another peak for the age group 70-79. During the study period, the prevalence of asthma and atopic dermatitis showed decreasing tendency. In contrast, the prevalence of allergic rhinitis steadily increased until 2013, especially in the age group under 10.
CONCLUSIONS The national prevalence of atopic dermatitis, and asthma did not show noticeable increase any more in Korea. However, the prevalence of allergic rhinitis still on the rise until recently, especially in the age group under 10. This is the first report in Asia suggesting a slowdown of the incidence of allergic diseases.
PubMed IF 6.2 알레르기내과
20112016

제1저자 최진우 · 교신저자 박경수

, , , , , , ,
DMC (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) improves glucose tolerance as a potent AMPK activator.
Metabolism. 2016;65(4):533-42.

Abstract
OBJECTIVE We investigated the effect and regulatory mechanism of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from Cleistocalyx operculatus on metabolic parameters in myotubes, adipocytes and an obese mouse model.
MATERIALS AND METHODS Myotubes and adipocytes were incubated with or without DMC. Glucose uptake, fatty acid oxidation, AMPK activation and adipocytes differentiation were investigated. To examine in vivo effect of DMC, 30mg/kg/day DMC was administered by oral gavage for 2weeks in high fat fed C57BL/6 male mice and intra-peritoneal glucose tolerance test was performed. In order to examine whether DMC directly activates AMPK, we performed cell free AMPK assay and surface plasmon resonance spectroscopy analysis.
RESULT DMC increases glucose uptake and fatty acid oxidation (FAO) in myotubes. Also, DMC inhibits adipocyte differentiation in 3T3-L1 cells. Interestingly, DMC stimulates phosphorylation of AMP-dependent protein kinase (AMPK) alpha subunit (T172) by directly binding to AMPK, which results in the activation of AMPK. Furthermore, DMC binds AMPK with a higher affinity than AMP. When AMPK was knocked down, the stimulatory effect of DMC on FAO and its inhibitory effect on adipogenesis were abolished. These results suggest that the effects of DMC were primarily mediated by AMPK activation. In addition, treating mice fed a high fat diet with DMC improved glucose tolerance and significantly increased FAO of the muscles.
CONCLUSION DMC, as a novel AMPK activator, shows anti-diabetic effects in cell culture systems, such as myotubes and adipocytes, and in a diet-induced obese mouse model.
PubMed IF 16.7 내분비대사내과
20102016

제1저자 오태정 · 교신저자 조영민

, ,
Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: Lessons from ileal transposition surgery.
J Diabetes Investig. 2016;7 Suppl 1(Suppl 1):94-101.

Abstract
Roux-en Y gastric bypass is a highly effective bariatric/metabolic surgical procedure that can induce robust weight loss and even remission of type 2 diabetes. One of the characteristic consequences of Roux-en Y gastric bypass is the expedited nutrient delivery to the distal small intestine, where L-cells are abundant and bile acid reabsorption occurs. To examine the role of the distal small intestine in isolation from other components of Roux-en Y gastric bypass, the ileal transposition (IT) surgery has been used in various rat models. IT relocates the distal ileal segment to the upper jejunum distal to the ligament of Treitz without any other alterations in the gastrointestinal anatomy. Therefore, IT exposes the distal ileal tissue to ingested nutrients after a meal faster than the normal condition. Although there is some inconsistency in the effect of IT according to different types of rat models and different types of surgical protocols, IT typically improved glucose tolerance, increased insulin sensitivity and induced weight loss, and the findings were more prominent in obese diabetic rats. Suggested mechanisms for the metabolic improvements after IT include increased L-cell secretion (e.g., glucagon-like peptides and peptide YY), altered bile acid metabolism, altered host-microbial interaction, attenuated metabolic endotoxemia and many others. Based on the effect of IT, we can conclude that the contribution of the distal small intestine to the metabolic benefits of bariatric/metabolic surgery is quite considerable. By unveiling the mechanism of action of IT, we might revolutionize the treatment for obesity and type 2 diabetes.
PubMed IF 3.6 내분비대사내과
20092016

제1저자 나선희 · 교신저자 김홍빈

, , , , , , , , , , , , ,
Impact of the multiplex polymerase chain reaction in culture-positive samples on appropriate antibiotic use in patients with staphylococcal bacteremia.
Diagn Microbiol Infect Dis. 2016;84(4):353-7.

Abstract
Rapid identification of the microorganisms in patients with bacteremia may be useful in clinical practice. We evaluated the impact of the multiplex polymerase chain reaction (PCR) on appropriate antibiotic use for patients with gram-positive cocci cluster (GPCC) bacteremia. We divided the GPCC bacteremia cases into a pre-PCR group (2010-2011) and a post-PCR group (2012-2013). A total 664 cases were included in the pre-PCR group; and 570, in the post-PCR group. In methicillin-susceptible Staphylococcus aureus (MSSA) cases, optimal antibiotics were administered earlier in the post-PCR group (77.4h versus 42.6h, P=0.035). Although the proportions of glycopeptide exposure did not differ (54.7% versus 56.7%, P=0.799), the duration of exposure decreased (69.6h versus 30.7h, P=0.004). In methicillin-resistant S. aureus cases, the time to optimal antibiotics administration did not differ (45.4h versus 43.7h, P=0.275). Multiplex PCR test significantly improved the early initiation of optimal antibiotics in MSSA bacteremia and reduced the unnecessary glycopeptide exposure.
PubMed IF 1.8 감염내과

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