SCI 발표논문

전체 4,588편

23982017

제1저자 신철민 · 교신저자 이동호

, , , , , ,
Association Among Obesity, Metabolic Health, and the Risk for Colorectal Cancer in the General Population in Korea Using the National Health Insurance Service-National Sample Cohort.
Dis Colon Rectum. 2017;60(11):1192-1200.

Abstract
BACKGROUND In Korea, the incidence of colorectal cancer has increased and obesity is on a rising trend because of a Westernized lifestyle in men.
OBJECTIVE The purpose of this study was to evaluate the relationship between metabolic health status, as well as BMI, and the incidence of colorectal cancer.
DESIGN This was a prospective cohort study.
SETTINGS The study was conducted with the National Health Insurance Service-National Sample Cohort.
PATIENTS A total of 408,931 Korean adults without cancer at baseline were followed up until 2013 (mean follow-up, 9 y).
MAIN OUTCOME MEASURES Demographic, anthropometric, and laboratory data at baseline were collected and categorized. The presence of diabetes mellitus, hypertension, and dyslipidemia was defined using the criteria of previous studies. The incidence of colorectal cancer was also defined according to the International Classification of Disease, 10 Revision, codes and the claim data on endoscopy with biopsy.
RESULTS During the follow-up, 5108 new cases of colorectal cancer occurred. Being underweight (<18.5 kg/m) reduced the risk for colorectal cancer among women (adjusted HR = 0.646 (95% CI, 0.484-0.863)), whereas high BMI significantly increased the risk in men and in the elderly. Obesity (≥25 kg/m), diabetes mellitus, and hypertension were identified as risk factors for colorectal cancer in men but not for women. Although metabolically unhealthy nonobese men had a higher risk for colorectal cancer than metabolically healthy nonobese men (adjusted HR = 1.114 (95% CI, 1.004-1.236)), the risk was lower than that in the obese men.
LIMITATIONS The study population consisted of people who underwent health examinations, thus there could be selection bias.
CONCLUSIONS In Korean adults, obesity contributes to the incidence of colorectal cancer with a sex difference. Nonobese but metabolically unhealthy men are considered to be a high-risk group for colorectal cancer, but obesity itself is more important in colorectal carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A475.
PubMed IF 3.1 소화기내과
23972017

제1저자 박상원 · 교신저자 Nuermberger E.

, , ,
Immunodeficiency and Intermittent Dosing Promote Acquired Rifamycin Monoresistance in Murine Tuberculosis.
Antimicrob Agents Chemother. 2017;61(11):AAC.01502-17.

Abstract
More-permissive preclinical models may be useful in evaluating antituberculosis regimens for their propensity to select drug-resistant mutants. To evaluate whether acquired rifamycin monoresistance could be recapitulated in mice and, if so, to evaluate the effects of immunodeficiency, intermittent dosing, and drug exposures, athymic nude and BALB/c mice were infected. Controls received daily rifapentine alone or 2 months of rifampin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampin/isoniazid, either daily or twice weekly with one of two isoniazid doses. Test groups received the same intensive regimen followed by once-weekly rifapentine or isoniazid/rifapentine with rifapentine doses of 10, 15, or 20 mg/kg of body weight plus one of two isoniazid doses. All combination regimens rendered BALB/c mouse cultures negative but selected mutants resistant to isoniazid (8.5%, 12/140) or rifampin (3.5%, 5/140) in nude mice (P < 0.001). Intermittently dosed intensive-phase therapy selected isoniazid and rifampin resistance in 10% (8/80, P < 0.001) and 20% (16/80, P = 0.009) of nude mice, respectively, compared to 0% treated with a daily regimen. Once-weekly rifapentine-containing continuation-phase regimens selected rifampin-resistant mutants at a rate of 18.0% (18/100, P = 0.035 compared to rifampin/isoniazid regimens). Higher isoniazid doses in the intermittent-treatment control regimen and higher rifapentine doses in once-weekly regimens were associated with less selection of isoniazid resistance. Acquired resistance, including rifamycin monoresistance, was more likely to occur in nude mice despite administration of combination therapy. These results recapitulate clinical outcomes and indicate that nude mice may be useful for evaluating the ability of novel regimens to prevent the selection of resistance.
PubMed IF 4.2 감염내과
23962017

제1저자 이민종, 정고은 · 교신저자 이정훈

, , , , , , , , , , , , , , , , ,
Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment.
Hepatology. 2017;66(5):1556-1569.

Abstract
UNLABELLED Antiplatelet therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether antiplatelet therapy lowers the risk of HCC in patients with chronic hepatitis B. A retrospective analysis was conducted of data from 1,674 chronic hepatitis B patients, enrolled between January 2002 and May 2015, whose serum hepatitis B virus DNA levels were suppressed by antivirals to <2,000 IU/mL. The primary and secondary outcomes were development of HCC and bleeding events, respectively. Risk was compared between patients with antiplatelet treatment (aspirin, clopidogrel, or both; antiplatelet group) and patients who were not treated (non-antiplatelet group) using a time-varying Cox proportional hazards model for total population and propensity score-matching analysis. The antiplatelet group included 558 patients, and the non-antiplatelet group had 1,116 patients. During the study period, 63 patients (3.8%) developed HCC. In time-varying Cox proportional analyses, the antiplatelet group showed a significantly lower risk of HCC (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.85; P = 0.01), regardless of antiplatelet agent. In propensity score-matched pairs, antiplatelet therapy significantly reduced the risk of HCC (HR, 0.34; 95% CI, 0.15-0.77; P = 0.01). However, the overall risk of bleeding was higher in the antiplatelet group (HR, 3.28; 95% CI, 1.98-5.42; P < 0.001), particularly for clopidogrel with or without aspirin. Treatment with aspirin alone was not associated with a higher bleeding risk (HR, 1.11; 95% CI, 0.48-2.54; P = 0.81).
CONCLUSION Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556-1569).
PubMed IF 18 소화기내과
23952017

제1저자 박준빈 · 교신저자 김형관

, , , , , , , ,
Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial.
Trials. 2017;18(1):501.

Abstract
BACKGROUND The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).
METHODS/DESIGN The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.
DISCUSSION In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.
TRIAL REGISTRATION ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.
PubMed IF 2.1 순환기내과
23942017

제1저자 정재훈, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , ,
Benefit of Vasodilating β-Blockers in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention: Nationwide Multicenter Cohort Study.
J Am Heart Assoc. 2017;6(10):JAHA.117.007063.

Abstract
BACKGROUND Although current guidelines recommend β-blocker after acute myocardial infarction (MI), the role of β-blocker has not been well investigated in the modern reperfusion era. In particular, the benefit of vasodilating β-blocker over conventional β-blocker is still unexplored.
METHODS AND RESULTS Using nation-wide multicenter Korean Acute Myocardial Infarction Registry data, we analyzed clinical outcomes of 7127 patients with acute MI who underwent successful percutaneous coronary intervention with stents and took β-blockers: vasodilating β-blocker (n=3482), and conventional β-blocker (n=3645). In the whole population, incidence of cardiac death at 1 year was significantly lower in the vasodilating β-blocker group (vasodilating β-blockers versus conventional β-blockers, 1.0% versus 1.9%; P=0.003). In 2882 pairs of propensity score-matched population, the incidence of cardiac death was significantly lower in the vasodilating β-blocker group (1.1% versus 1.8%; P=0.028). Although incidences of MI (1.1% versus 1.5%; P=0.277), any revascularization (2.8% versus 3.0%; P=0.791), and hospitalization for heart failure (1.4% versus 1.9%; P=0.210) were not different between the 2 groups, incidences of cardiac death or MI (2.0% versus 3.1%; P=0.010), cardiac death, MI, or hospitalization for heart failure (3.0% versus 4.5%; P=0.003), cardiac death, MI, or any revascularization (3.9% versus 5.3%; P=0.026), and cardiac death, MI, any revascularization, or hospitalization for heart failure (4.8% versus 6.5%; P=0.011) were significantly lower in the vasodilating β-blocker group.
CONCLUSIONS Vasodilating β-blocker therapy resulted in better clinical outcomes than conventional β-blocker therapy did in patients with acute MI in the modern reperfusion era. Vasodilating β-blockers could be recommended preferentially to conventional ones for acute MI patients.
PubMed IF 6 순환기내과
23932017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Similarity and Difference of Resting Distal to Aortic Coronary Pressure and Instantaneous Wave-Free Ratio.
J Am Coll Cardiol. 2017;70(17):2114-2123.

Abstract
BACKGROUND Instantaneous wave-free ratio (iFR) has been used in clinical practice to identify functionally significant stenosis and to guide treatment strategy. However, there are limited clinical data regarding another resting pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and similarities and differences between resting Pd/Pa and iFR.
OBJECTIVES The authors investigated the changes in resting Pd/Pa and iFR according to anatomic and hemodynamic stenosis severity and their prognostic implications.
METHODS From the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with available pre-intervention resting Pd/Pa and iFR were used to explore the changes in resting physiological indices according to percent diameter stenosis. Among 115 patients who underwent ¹³N-ammonia positron emission tomography, the changes in those indices according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between physiological indices and the risk of 2-year major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) were analyzed among 375 deferred patients.
RESULTS There was a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p < 0.001, iFR = 1.370 × resting Pd/Pa - 0.370). Both resting Pd/Pa and iFR changed significantly according to percent diameter stenosis, basal and hyperemic stenosis resistance, and hyperemic absolute myocardial blood flow (all p values <0.001). Percent difference of iFR according to the increase in anatomic and hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa and iFR showed a significant association with the risk of 2-year MACE (resting Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to 0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the difference between the upper- and lower-bound estimated MACE rates according to the approximate measurement variability of each index was significantly higher with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 ± 4.00% and iFR 3.27 ± 3.39%; p < 0.001).
CONCLUSIONS Both resting Pd/Pa and iFR showed similar associations with anatomic and hemodynamic stenosis severity and the risk of MACE. However, iFR was more sensitive to the difference in stenosis severity and showed a lower maximum difference in estimated MACE risk influenced by the measurement variability compared with resting Pd/Pa. (Clinical Implication of 3-Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR]; NCT01366404).
PubMed IF 22.3 순환기내과
23922017

제1저자 이소령 · 교신저자 최의근

, , , ,
Association between γ-glutamyltransferase level and incidence of atrial fibrillation: A nationwide population-based study.
Int J Cardiol. 2017;245:149-155.

Abstract
BACKGROUND Information on the association between γ-glutamyltransferase (GGT) and the incidence of atrial fibrillation (AF) is scarce. We evaluated the association between GGT and AF incidence, and the interaction between GGT and obesity on developing AF in a large population-based cohort.
METHODS We evaluated 266,550 individuals (mean age, 53±11; men, 48.4%) who underwent the national insurance health checkup between 2004 and 2008. Subjects were categorized in accordance with quartiles of GGT levels (range: Q1, 0-15U/L; Q2, 16-22U/L; Q3, 23-38U/L; Q4, ≥39U/L). The association between GGT levels and AF incidence was analyzed by using multivariable Cox proportional-hazards regression models.
RESULTS During a median of 8years' follow-up, 5034 individuals (1.9%) were newly diagnosed with AF. The crude AF incidence gradually increased with increases in GGT level (1.9, 2.5, 2.8, and 3.1 per 1000 person-years in the Q1, Q2, Q3, and Q4 GGT groups, respectively; p for trend <0.001). In the multivariable Cox proportional hazard models, GGT level showed a dose-response relationship with AF incidence. The subjects with the highest quartile of GGT levels had a significantly higher risk of AF (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18-1.45; p<0.001). When the analysis was stratified by body mass index (BMI), GGT level showed good discrimination for AF incidence only in the non-obese population (BMI<25kg/m²), and not in the obese population (BMI≥25kg/m²; p interaction<0.001).
CONCLUSIONS In this large population-based study, elevated GGT level showed a significant association with increased risk of AF, especially in a non-obese population.
PubMed IF 3.3 순환기내과
23912017

제1저자 이주명 · 교신저자 구본권

, , , , , , , ,
Discrepancy between fractional flow reserve and instantaneous wave-free ratio: Clinical and angiographic characteristics.
Int J Cardiol. 2017;245:63-68.

Abstract
BACKGROUND The invasive physiologic index such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) is used in clinical practice to identify ischemia-causing stenosis and to guide treatment strategy. We investigated clinical and angiographic characteristics of lesions with discrepancy between FFR and iFR.
METHODS From the 3V FFR-FRIENDS study, 975 vessels (393 patients) with available pre-intervention FFR and iFR were included in this study. The vessels were classified according to FFR and iFR into: concordant normal (Group 1 [n=724]: FFR>0.80 and iFR≥0.90); high FFR and low iFR (Group 2 [n=33]: FFR>0.80 and iFR<0.90); low FFR and high iFR (Group 3 [n=82]: FFR≤0.80 and iFR≥0.90); and concordant abnormal (Group 4 [n=136]: FFR≤0.80 and iFR<0.90).
RESULTS Angiographic stenosis severity assessed by percent diameter stenosis, minimum lumen diameter and lesion length was increased from Group 1 to Group 4 (all p<0.001). SYNTAX score increased and FFR decreased proportionally from Group 1 to Group 4 (all p<0.001). In multivariable GEE model, female, diabetes mellitus, smaller reference vessel diameter, and higher %DS were significantly associated with low iFR among high FFR groups (Group 2 discordance). Conversely, males, absence of diabetes mellitus and lower %DS were significantly associated with high iFR among low FFR groups (Group 3 discordance).
CONCLUSIONS Four groups classified according to FFR and iFR were different in clinical and angiographic characteristics, SYNTAX score, and predictors of discordance. The lesions with discordant FFR and iFR may need to be interpreted as a different clinical entity.
PubMed IF 3.3 순환기내과
23902017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Prognosis of deferred non-culprit lesions according to fractional flow reserve in patients with acute coronary syndrome.
EuroIntervention. 2017;13(9):e1112-e1119.

Abstract
AIMS There are limited data on the prognosis of deferred non-culprit lesions in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR). We aimed to investigate the prognosis of deferred non-culprit lesions in ACS patients, compared with deferred lesions in patients with stable coronary artery disease (SCAD), on the basis of FFR.
METHODS AND RESULTS The clinical outcomes of 449 non-culprit lesions (301 patients with ACS) were compared with 2,484 lesions (1,295 patients with SCAD) in which revascularisation was deferred on the basis of a high FFR (>0.80). The primary outcome was major adverse cardiac events (MACE), a composite of cardiac death, target vessel-related myocardial infarction (MI) and ischaemia-driven revascularisation. Among the ACS population, 65.8% presented with unstable angina and 34.2% with non-ST-segment elevation MI. Mean angiographic percent diameter stenosis and FFR of the deferred lesions were 39.3±15.0% and 0.92±0.06, respectively. During the median follow-up duration of 722.0 days, the deferred non-culprit lesions of ACS patients showed a significantly higher rate of MACE (3.8% vs. 1.6%, HRadj 2.97, 95% CI: 1.23-7.17, p=0.016), mainly driven by the higher rate of ischaemia-driven revascularisation (2.8% vs. 1.1%, HRadj 3.39, 95% CI: 1.29-8.92, p=0.013) than the deferred lesions in SCAD patients. Regardless of the range of FFR in the deferred lesions (0.81-0.85, 0.86-0.90, 0.91-0.95, and 0.95-1.00), non-culprit lesions of ACS showed a more than twofold higher rate of MACE than that of SCAD. In a multivariable marginal Cox model, ACS was the most powerful independent predictor of MACE (HRadj 2.74, 95% CI: 1.13-6.64, p=0.026).
CONCLUSIONS Compared to the deferred lesions of SCAD patients, deferred non-culprit lesions of ACS on the basis of FFR showed a higher rate of clinical events, regardless of FFR range.
PubMed IF 9.2 순환기내과
23892017

제1저자 김치훈, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , , , ,
Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis - coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial.
BMJ Open. 2017;7(10):e016617.

Abstract
INTRODUCTION We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies.
METHODS AND ANALYSIS The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding.
ETHIC APPROVAL AND DISSEMINATION All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers.
TRIAL REGISTRATION NUMBER NCT02601157; Pre-results.
PubMed IF 2.5 순환기내과
23882017

제1저자 우현구 · 교신저자 김윤준

, , , , , , , , , , ,
Integrative analysis of genomic and epigenomic regulation of the transcriptome in liver cancer.
Nat Commun. 2017;8(1):839.

Abstract
Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients.Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.
PubMed IF 18.1 소화기내과
23872017

제1저자 온정헌, 황지연 · 교신저자 문민경

, , , , , , , , , ,
Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice.
PLoS One. 2017;12(10):e0186021.

Abstract
The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0.05). Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPARγ1 and PPARα were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.
PubMed IF 2.8 내분비대사내과
23862017

제1저자 박세훈 · 교신저자 임춘수

, , , , , , ,
Association between postoperative hyponatremia and renal prognosis in major urologic surgery.
Oncotarget. 2017;8(45):79935-79947.

Abstract
Recent evidence for the clinical significance of postoperative hyponatremia after urologic surgeries remains scarce. We examined the incidence, risk factors, and outcomes of electrolyte imbalance in urologic surgery. Patients with newly developed hyponatremia, defined as a sodium level lower than 135 mEq/L within 7 days after surgery, were included in our study group. The primary outcome was progression to end-stage renal disease (ESRD). Secondary outcome was composition of progression to ESRD and creatinine doubling/eGFR halving from baseline. A survival analysis with a multivariable Cox proportional hazard model was performed. We included 9,206 cases of bladder, prostate, ureter, and kidney surgery. Incidence of new-onset postoperative hyponatremia was 15.4% (1,414/9,206). Postoperative hyponatremia mostly developed in patients with high-risk perioperative characteristics. The development of postoperative hyponatremia was independently associated with progression to ESRD (adjusted HR 1.343, 95% CI 1.082-1.680, P = 0.007). The secondary outcome was also related to the electrolyte imbalance in prostate (adjusted HR 1.729, 95% CI 1.145-2.612, P = 0.009) and kidney (adjusted HR 1.339, 95% CI 1.099-1.632, P = 0.004) surgery. Postoperative hyponatremia in urologic surgery was a common electrolyte imbalance in patients with high-risk perioperative status, and associated with worse renal prognosis.
PubMed IF 5.168 신장내과
23852017

제1저자 조경민 · 교신저자 오도연

, , , , , , , ,
Skeletal muscle depletion predicts survival of patients with advanced biliary tract cancer undergoing palliative chemotherapy.
Oncotarget. 2017;8(45):79441-79452.

Abstract
BACKGROUND No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI).
RESULTS By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m²) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576).
MATERIALS AND METHODS We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm²) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm²/m² (men) and < 39.5 cm²/m² (women) using ROC curves.
CONCLUSIONS Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC.
PubMed IF 5.168 혈액종양내과
23842017

제1저자 Kohei Shitara · 교신저자 방영주

, , , , , , , , , , , , ,
Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.
Oncotarget. 2017;8(45):79546-79555.

Abstract
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m²) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort (N = 19; unselected population, including three patients with MET-amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m². Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m² in the dose-expansion cohort, comprising patients with MET-amplified tumors (N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m² has acceptable tolerability and modest antitumor activity in patients with MET-amplified gastric cancer.
PubMed IF 5.168 혈액종양내과
23832017

제1저자 이희선 · 교신저자 박준빈

, , , , , , , , , , , , , , , ,
Impact of a Telehealth Program With Voice Recognition Technology in Patients With Chronic Heart Failure: Feasibility Study.
JMIR Mhealth Uhealth. 2017;5(10):e127.

Abstract
BACKGROUND Despite the advances in the diagnosis and treatment of heart failure (HF), the current hospital-oriented framework for HF management does not appear to be sufficient to maintain the stability of HF patients in the long term. The importance of self-care management is increasingly being emphasized as a promising long-term treatment strategy for patients with chronic HF.
OBJECTIVE The objective of this study was to evaluate whether a new information communication technology (ICT)-based telehealth program with voice recognition technology could improve clinical or laboratory outcomes in HF patients.
METHODS In this prospective single-arm pilot study, we recruited 31 consecutive patients with chronic HF who were referred to our institute. An ICT-based telehealth program with voice recognition technology was developed and used by patients with HF for 12 weeks. Patients were educated on the use of this program via mobile phone, landline, or the Internet for the purpose of improving communication and data collection. Using these systems, we collected comprehensive data elements related to the risk of HF self-care management such as weight, diet, exercise, medication adherence, overall symptom change, and home blood pressure. The study endpoints were the changes observed in urine sodium concentration (uNa), Minnesota Living with Heart Failure (MLHFQ) scores, 6-min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as surrogate markers for appropriate HF management.
RESULTS Among the 31 enrolled patients, 27 (87%) patients completed the study, and 10 (10/27, 37%) showed good adherence to ICT-based telehealth program with voice recognition technology, which was defined as the use of the program for 100 times or more during the study period. Nearly three-fourths of the patients had been hospitalized at least once because of HF before the enrollment (20/27, 74%); 14 patients had 1, 2 patients had 2, and 4 patients had 3 or more previous HF hospitalizations. In the total study population, there was no significant interval change in laboratory and functional outcome variables after 12 weeks of ICT-based telehealth program. In patients with good adherence to ICT-based telehealth program, there was a significant improvement in the mean uNa (103.1 to 78.1; P=.01) but not in those without (85.4 to 96.9; P=.49). Similarly, a marginal improvement in MLHFQ scores was only observed in patients with good adherence (27.5 to 21.4; P=.08) but not in their counterparts (19.0 to 19.7; P=.73). The mean 6-min walk distance and NT-proBNP were not significantly increased in patients regardless of their adherence.
CONCLUSIONS Short-term application of ICT-based telehealth program with voice recognition technology showed the potential to improve uNa values and MLHFQ scores in HF patients, suggesting that better control of sodium intake and greater quality of life can be achieved by this program.
PubMed IF 6.3 순환기내과
23822017

제1저자 박상원 · 교신저자 박상원

, , , ,
Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unit using peer tutoring.
Antimicrob Resist Infect Control. 2017;6:103.

Abstract
BACKGROUND Central line-associated bloodstream infections (CLABSIs) can be prevented through well-coordinated, multifaceted programs. However, implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy in resource-limited settings is uncertain. Peer tutoring may be an efficient and effective method that is applicable in such settings.
METHODS A prospective intervention was performed to reduce CLABSIs in a surgical intensive care unit (SICU) at a tertiary hospital. The core interventions consisted of implementation of insertion and maintenance bundles for CLABSI prevention. The overall interventions were guided and coordinated by active educational programs using peer tutoring. The CLABSI rates were compared for 9 months pre-intervention, 6 months during the intervention and 9 months post-intervention. The CLABSI rate was further observed for three years after the intervention.
RESULTS The rate of CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre-intervention period to 2.4 and 1.8 in the intervention (6 m; P = 0.102) and post-intervention (9 m; P = 0.036) periods, respectively. A regression model showed a significantly decreasing trend in the infection rate from the pre-intervention period (P < 0.001), with incidence-rate ratios of 0.348 (95% confidence interval [CI], 0.98-1.23) in the intervention period and 0.257 (95% CI, 0.07-0.91) in the post-intervention period. However, after the 9-month post-intervention period, the yearly CLABSI rates reverted to 3.0-5.4 infections per 1000 catheter-days over 3 years.
CONCLUSIONS Implementation of CLABSI prevention bundles using peer tutoring in a resource-limited setting was useful and effectively reduced CLABSIs. However, maintaining the reduced CLABSI rate will require further strategies.
PubMed IF 5.2 감염내과
23812017

제1저자 김윤지 · 교신저자 임수

, , , , , , , ,
Association Between Obesity and Chronic Kidney Disease, Defined by Both Glomerular Filtration Rate and Albuminuria, in Korean Adults.
Metab Syndr Relat Disord. 2017;15(8):416-422.

Abstract
BACKGROUND Chronic kidney disease (CKD) has often been defined based on glomerular filtration rate (GFR) alone. The Kidney Disease: Improving Global Outcomes guideline highlights albuminuria in the CKD definition. Thus, we investigated the association between obesity and CKD, as defined by both GFR and albuminuria, in Korean adults.
METHODS We used Korea National Health and Nutrition Examination Survey 2011-2014 data (N = 19,331, ≥19 years old) representing the national Korean population. CKD was classified by (1) estimated GFR (eGFR) < 60 mL/min/1.73 m² (CKD_GFR); (2) albumin-to-creatinine ratio (ACR) ≥30 mg/gram (CKD_ACR); and (3) eGFR < 60 mL/min/1.73 m² or ACR ≥30 mg/gram (CKD_Risk). Associations between obesity and each CKD category were evaluated using multivariate logistic regression analysis.
RESULTS The prevalence rates of CKD_GFR, CKD_ACR, and CKD_Risk were 2.2%, 6.7%, and 8.1%, respectively. Compared with the normal body mass index (BMI; 18.5-22.9 kg/m²) group, men with BMI ≥ 25 kg/m² had 1.88 times greater risk of CKD_GFR in the adjusted model [95% confidence interval (CI), 1.26-2.80; P = 0.002]; BMI was not significantly associated with CKD_GFR in women. In contrast, both men and women with BMI ≥ 25 kg/m² had 1.58 and 1.40 times higher risk of CKD_ACR (95% CI, 1.21-2.07 and 1.08-1.81, respectively, both P < 0.01). Obese men and women had 1.65 and 1.38 times higher risk of CKD_Risk (95% CI, 1.29-2.12 and 1.09-1.75, respectively, both P < 0.01).
CONCLUSIONS Obesity was significantly associated with an increased ACR-based CKD risk. Longitudinal studies are needed to investigate the role of overweight and obesity in the development and progression of CKD.
PubMed IF 1.6 내분비대사내과
23802017

제1저자 지명진 · 교신저자 김정희

, , , , , , ,
Best candidates for dopamine agonist withdrawal in patients with prolactinomas.
Pituitary. 2017;20(5):578-584.

Abstract
PURPOSE Dopamine agonist (DA) therapy is recommended as the first-line treatment for prolactinomas. However, it requires long treatment duration, and a high recurrence rate after DA withdrawal has been reported. We aimed to elucidate the predictors for long-term remission following DA withdrawal and propose the best candidates who can achieve complete remission after DA withdrawal.
METHODS In a retrospective cohort study, we included 89 patients with prolactinoma who have withdrawn DAs with normal prolactin (PRL) levels at Seoul National University Hospital, from 2000 to 2016. Patient's data were retrieved from the electronic medical records.
RESULTS The median age and median treatment duration of the study patients were 33 (15-73) years and 69.5 (8.3-277.4) months, respectively. The recurrence rate after drug withdrawal was 57.3% during the 23.9 (3.0-176.8) month follow-up period. Age, gender, baseline PRL level, and baseline maximum tumor diameter were similar between the remission and recurrence group. In the Cox-proportional hazard model analysis, the significant predictors for remission were nadir PRL level of <1 ng/dL (hazard ratio [95% confidence interval] = 0.37 [0.18-0.74]), invisible tumors on magnetic resonance imaging (MRI) (0.42 [0.24-0.74]), and treatment duration of >72 months (0.54 [0.30-0.96]). Of the subjects who met all the three criteria, 66.7% achieved long-term remission.
CONCLUSIONS Patients who have no tumor visible on MRI, have a nadir PRL level <1 ng/dL during drug treatment, and received drug treatment for >6 years may be the best candidates for DA withdrawal.
PubMed IF 3.8 내분비대사내과
23792017

제1저자 방영주 · 교신저자 방영주, Markus Moehler

, , , , , , , , ,
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer.
Clin Cancer Res. 2017;23(19):5671-5678.

Abstract
Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS).Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61-5.16 vs. 4.90 months, 95% CI, 3.45-6.54, HR = 1.44; 80% CI, 1.09-1.91; P = 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5-18.9) and 12.1 months (95% CI, 9.3-not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients.Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer. Clin Cancer Res; 23(19); 5671-8. ©2017 AACR.
PubMed IF 10.9 혈액종양내과
23782017

제1저자 민세희 · 교신저자 임수

, , , , , , , ,
Association of angiotensin-II levels with albuminuria in subjects with normal glucose metabolism, prediabetes, and type 2 diabetes mellitus.
J Diabetes Complications. 2017;31(10):1499-1505.

Abstract
OBJECTIVES The relationship between the renin-angiotensin system (RAS) and diabetes has been studied for many years. However, studies that assessed RAS components comprehensively were limited. We hypothesized that serum RAS components, especially the effector peptide angiotensin-II, might be closely associated with glucose metabolism status and diabetic complications.
METHODS We investigated the association of individual RAS component with albuminuria in 407 subjects with normal glucose metabolism (NGM), prediabetes, or type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters, including glucose homeostasis, albuminuria, and RAS-related parameters such as plasma renin activity (PRA), aldosterone, angiotensin-converting enzyme (ACE), and angiotensin-II levels, were measured.
RESULTS The mean±standard deviation (SD) age and body mass index were 57.1±11.1years and 24.7±3.3kg/m², respectively. There were 54 subjects with NGM, 102 with prediabetes, and 251 with T2DM. The mean±SD angiotensin-II levels in these groups were 9.32±6.89, 12.89±10.39, and 17.00±15.28pg/mL, and the respective urinary albumin-to-creatinine ratios (ACRs) were 8.1±5.3, 13.3±17.3, and 30.7±51.9mg/g, which were significantly different among the groups. The serum angiotensin-II levels were correlated with levels of PRA, insulin resistance, C-reactive protein, and urinary ACR. Among RAS-related parameters, only the angiotensin-II level was significantly associated with urinary ACR after adjusting for relevant risk factors.
CONCLUSIONS Angiotensin-II may play an important role in the development of albuminuria, particularly in subjects with impaired glucose metabolism.
PubMed IF 3.2 내분비대사내과
23772017

제1저자 황성욱, 김지현 · 교신저자 임종필

, , , , , , , , , , , ,
Influence of age at diagnosis on the clinical characteristics of Crohn's disease in Korea: Results from the CONNECT study.
J Gastroenterol Hepatol. 2017;32(10):1716-1722.

Abstract
BACKGROUND AND AIM The present study evaluated the clinical characteristics of Korean patients with Crohn's disease (CD) according to their age at diagnosis in a nationwide multicenter cohort study.
METHODS A total of 1224 patients diagnosed with CD between 1982 and 2008 in 32 hospitals were included, and age at diagnosis was categorized as ≤ 16 (G1), 17-40 (G2), 41-59 (G3) and ≥ 60 (G4) years old. The baseline characteristics, medication, and intestinal resection were compared according to the age at diagnosis.
RESULTS The number of patients in each age group was 155 (G1; 12.7%), 919 (G2; 75.1%), 120 (G3; 9.8%), and 30 (G4; 2.5%). The frequencies of ileocolonic disease in the late adult onset and elderly onset groups were lower than those in the other groups (P < 0.001). The cumulative probabilities of thiopurine and anti-tumor necrosis factor use in late adult onset and elderly onset groups were significantly reduced compared with those of the other groups (P < 0.01). However, the risk of the first intestinal resection was not different among the age groups. The ileal location (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.27), complicated behavior (HR: 3.35; 95% CI: 2.63-4.27), and early thiopurine use (HR: 0.27; 95% CI: 0.17-0.43) were associated with the first intestinal resection, whereas the age at diagnosis was not a risk factor.
CONCLUSIONS Elderly onset CD may be related to favorable outcomes in Korea. Thus, the heterogeneity of this disease should be considered when developing a tailored strategy for the treatment of CD.
PubMed IF 3.5 소화기내과
23762017

제1저자 김세훈, 강시혁 · 교신저자 연태진

, , , , , , , , , , , , , , , , , ,
Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.
J Hypertens. 2017;35(10):1976-1982.

Abstract
OBJECTIVE Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose.
METHODS We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose.
RESULTS The mean age of the study population was 45.4 ± 0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine.
CONCLUSION Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.
PubMed IF 5.6 순환기내과
23752017

제1저자 이소령, 채인호 · 교신저자 김효수, 김상현

, , , , ,
Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.
Cardiovasc Ther. 2017;35(5):e12291.

Abstract
INTRODUCTION AND AIMS Endothelial dysfunction and arterial stiffness have a prognostic value on adverse long-term outcomes in coronary artery disease (CAD) patients. We evaluated the efficacy on vascular reactivity of candesartan and analyzed predictors to control the candesartan's effect on vascular reactivity in CAD patients.
METHOD Patients were prospectively enrolled and prescribed candesartan for 6 months. The effect on vascular reactivity was evaluated by the change in flow-mediated dilation (FMD) and pulse wave velocity (PWV).
RESULTS A total of 124 patients completed the study. The better responder in FMD change (≥1.3%) showed significantly lower baseline FMD than the poor responder (P < .001). In receiver operating characteristic analysis, baseline FMD 7.5% showed optimal predictive value (sensitivity 79%, specificity 79%) for predicting better responder. The baseline endothelial dysfunction (FMD <7.5%) was the only significant predictor of the better responder to candesartan. The better responder in PWV change (≤-100 cm/s) showed greater blood pressure lowering and significantly higher baseline PWV than the poor responder (both P < .05). The poor responder in both FMD and PWV showed a higher prevalence of previous myocardial infarction (38.7% vs 17.2%, P = .013).
CONCLUSION The candesartan's effect on vascular reactivity is more pronounced in patients with more severe endothelial dysfunction and arterial stiffness. Poor responders on both FMD and PWV showed higher prevalence of previous myocardial infarction.
PubMed IF 2.8 순환기내과
23742017

제1저자 임수 · 교신저자 최동섭

, , , , , , , , , , ,
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks.
Diabetes Metab J. 2017;41(5):377-385.

Abstract
BACKGROUND The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.
METHODS A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).
RESULTS During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (-0.85%±0.36% and -0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by -0.32% at the femur neck and by -0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.
CONCLUSION Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.
PubMed IF 8.2 내분비대사내과
23732017

제1저자 서경진 · 교신저자 김지현

, , , , , , , , , , , , , , ,
Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor-Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors.
Cancer Res Treat. 2017;49(4):1153-1163.

Abstract
PURPOSE Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
MATERIALS AND METHODS We retrospectively analyzed data of 66 premenopausal patients with hormone receptor- positive, human epidermal growth factor receptor 2-negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
RESULTS The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
CONCLUSION Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.
PubMed IF 4.2 혈액종양내과
23722017

제1저자 곽낙원 · 교신저자 임재준

, , , , ,
Treatment Outcomes of Mycobacterium avium Complex Lung Disease: A Systematic Review and Meta-analysis.
Clin Infect Dis. 2017;65(7):1077-1084.

Abstract
BACKGROUND The advent of macrolides has led to therapeutic advances in the treatment of Mycobacterium avium complex lung disease (MAC-LD). The aim of this study was to elucidate the treatment outcomes of macrolide-containing regimens.
METHODS We performed a systematic review and meta-analysis of published studies reporting treatment outcomes of macrolide-containing regimens for MAC-LD using the Medline, Embase, and Cochrane Library databases through 31 July 2016. The rates of treatment success, default from treatment, and adverse events of macrolide-containing regimens were assessed. Treatment success was defined as either 12 months of sustained culture negativity while on therapy or achievement of culture conversion and completion of the planned treatment without relapse.
RESULTS In total, 16 studies involving 1462 patients were included. The rate of treatment success was 60.0% (95% confidence interval [CI], 55.1%-64.8%). The proportion of patients who defaulted from the treatment was 16.0% (95% CI, 12.3%-19.7%). When a thrice-weekly dosing schedule was available, the default rate was 12.0% (95% CI, 8.9%-15.0%). Adverse events necessitating treatment discontinuation or dosage modification of macrolides were observed in 6.4% of patients (95% CI, 3.2%-9.5%), and decreased auditory acuity was the most common adverse event.
CONCLUSIONS Treatment outcomes of macrolide-containing regimens are relatively poor in terms of both the treatment success and default rates. The default rate could be reduced if a thrice-weekly dosing schedule is available. Clinicians should be aware of decreased auditory function as the most common adverse event associated with macrolide-containing regimens.
PubMed IF 8.3 호흡기내과
23712017

제1저자 박한기 · 교신저자 강혜련

, , , , ,
Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea.
Allergol Int. 2017;66(4):557-562.

Abstract
BACKGROUND Epidemiology and risk factors of drug-induced anaphylaxis are difficult to estimate due to lack of confirmative diagnosis and under reporting. Here we report the current state of drug-induced anaphylaxis in Korea based on an in-hospital pharmacovigilance database in a tertiary hospital.
METHODS This study is a retrospective analysis of drug-induced anaphylaxis, reported to an in-hospital pharmacovigilance center in Seoul National University Hospital from June 2009 to May 2013. Anaphylaxis occurred in patients under 18 years of age or developed by medications administered from outside pharmacies or hospitals were excluded. We assessed causative drug, incidence per use of each drug and risk factors of fatal anaphylactic shock.
RESULTS A total of 152 in-hospital drug-induced anaphylaxis cases were reported during the study period. The single most frequently reported drug was platinum compound and the incidence of anaphylaxis and anaphylactic shock in platinum compounds users was 2.84 and 1.39 per 1000 patients use. Risk factors of anaphylactic shock among total anaphylaxis cases were identified as older age ≥70 years [Odd's ratio (OR), 5.86; 95% confidence interval (CI), 1.70-20.14]. The use of iodinated contrast media (OR, 6.19; 95% CI, 1.87-20.53) and aminosteroid neuromuscular blocking agent (NMBA) (OR, 12.82; 95% CI, 1.50-109.92) were also a risk factor for the development of anaphylactic shock.
CONCLUSIONS Platinum compounds are the most commonly reported causative agents of in-hospital drug-induced anaphylaxis. Older age ≥70 years and drugs such as iodinated contrast media and aminosteroid NMBA are related with high risk of anaphylactic shock.
PubMed IF 6.2 알레르기내과
23702017

제1저자 박재용 · 교신저자 김상균

, , , , , , , ,
Risk factors for early metachronous tumor development after endoscopic resection for early gastric cancer.
PLoS One. 2017;12(9):e0185501.

Abstract
BACKGROUND Metachronous gastric tumor (MGT) is one of major concerns after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Optimal follow-up strategy has not been yet well-established. The aim of this study was to identify the different clinical features of the patients according to the time interval to development of MGT.
METHODS Among 1,780 consecutive patients with EGC who underwent ESD between 2005 and 2014, 115 patients with MGT were retrospectively reviewed. MGT was defined as secondary gastric cancer or dysplasia detected > 1 year after initial ESD. Clinicopathological factors associated with early development of MGT were evaluated.
RESULTS The median interval to development of MGT was 37 months. In univariate analysis, the median interval to MGT was shorter if EGC lesion was non-elevated type (39.4 vs 57.0 months, p = 0.011), or synchronous primary lesion was absent (39.8 vs 51.4 months, p = 0.050). In multivariate Cox's proportional hazards analysis, the hazard ratios for early occurrence of MGT were 1.966 (95% CI: 1.141-3.386, p = 0.015) and 1.911 (95% CI: 1.163-3.141, p = 0.011), respectively. There was no significant difference in overall survival after diagnosis of MGT between the early occurrence group and the late occurrence group.
CONCLUSIONS Non-elevated gross type and absence of synchronous gastric tumor were independent risk factors for early development of MGT. Meticulous endoscopic inspection is especially important for the detection of MGT during the early follow-up period in patients with these initial tumor characteristics.
PubMed IF 2.8 소화기내과
23692017

제1저자 조은주 · 교신저자 김윤준

, , , , , ,
Current status and strategies for hepatitis B control in Korea.
Clin Mol Hepatol. 2017;23(3):205-211.

Abstract
Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.
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