SCI 발표논문

1. 24882018

   제1저자 변자민 · 교신저자 윤성수

   Byun JM, Shin DY, Hong J, Kim I, Kim HK, Lee DS, Koh Y, Yoon SS

   Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response: redefining high-risk multiple myeloma in Asian patients.

   Cancer Med. 2018;7(3):831-841.

   Abstract

   For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and t(14;16) was associated with worse overall survival. Interestingly, however, the presence of t(4;14) conferred little prognostic impact. Treatment-specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation (autoSCT) was less effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly universal, but predictive marker del(13q14) and del(9p21) for lenalidomide response appears ethnicity-specific. Thus, FISH profiles in MM treatment should be interpreted with regards to patient's ethnicity.

   PubMed IF 3.5 혈액종양내과
2. 24872018

   제1저자 김민석 · 교신저자 김학령

   Kim M, Kim MA, Kim HL, Lee WJ, Lim WH, Seo JB, Kim SH, Zo JH

   Body mass index and the risk of low femoral artery puncture in coronary angiography under fluoroscopy guidance.

   Medicine (Baltimore). 2018;97(9):e0070.

   Abstract

   The inferior border of the femoral head (IBFH) is widely used as a landmark in femoral artery puncture during invasive coronary angiography (ICA). However, application of this technique can be challenging especially in obese patients. This study was performed to investigate the association between body mass index (BMI) and the risk of low puncture in femoral artery puncture.A total of 464 patients (64.8 ± 11.1 years, 55.8% male) who underwent ICA via trans-femoral access were retrospectively reviewed. IBFH was used as a landmark for a skin nick and the femoral artery cannulation site was confirmed by femoral angiography. Cannulation at the bifurcation of the common femoral artery (CFA) or below were considered low puncture.Twenty-nine patients (5.8%) were identified as having an angiographically high CFA bifurcation and low femoral artery puncture occurred in 27 (93.1%) patients of them. Among patients with normal bifurcation (n = 464), low puncture occurred in 74 (15.9%) patients. Underweight (BMI < 18.5 kg/m) or obese (BMI ≥ 30 kg/m) patients were more common in the low puncture group than in the proper puncture group (36.5% vs. 5.9%, P < .001). Multivariable analysis showed underweight or obesity (odd ratio, 9.10; 95% confidential interval, 4.77-17.35; P < .001) was an independent risk factor of low puncture even after controlling for clinical covariates. The average distance from IBFH to the CFA puncture site was shorter in patients with underweight (1.74 ± 0.71 cm) or obesity (1.75 ± 0.60 cm) than in those with normal BMI or overweight (2.07 ± 0.83 cm) (P = .030). Trigonometric calculation showed that the average distance from IBFH to the CFA puncture site was 0.5 to 2.59 cm (mean = 1.32 cm) shorter in underweight patients compared with those of normal weight or overweight patients.In patients with normal CFA bifurcation, underweight or obesity were associated with increased risk of low puncture. The puncture site should be chosen about 1 finger width more proximal to IBFH for ICA in such patients.

   PubMed IF 2 순환기내과
3. 24862018

   제1저자 강시혁 · 교신저자 서정원

   Kang SH, Joe B, Yoon Y, Cho GY, Shin I, Suh JW

   Cardiac Auscultation Using Smartphones: Pilot Study.

   JMIR Mhealth Uhealth. 2018;6(2):e49.

   Abstract

   BACKGROUND Cardiac auscultation is a cost-effective, noninvasive screening tool that can provide information about cardiovascular hemodynamics and disease. However, with advances in imaging and laboratory tests, the importance of cardiac auscultation is less appreciated in clinical practice. The widespread use of smartphones provides opportunities for nonmedical expert users to perform self-examination before hospital visits.

   OBJECTIVE The objective of our study was to assess the feasibility of cardiac auscultation using smartphones with no add-on devices for use at the prehospital stage.

   METHODS We performed a pilot study of patients with normal and pathologic heart sounds. Heart sounds were recorded on the skin of the chest wall using 3 smartphones: the Samsung Galaxy S5 and Galaxy S6, and the LG G3. Recorded heart sounds were processed and classified by a diagnostic algorithm using convolutional neural networks. We assessed diagnostic accuracy, as well as sensitivity, specificity, and predictive values.

   RESULTS A total of 46 participants underwent heart sound recording. After audio file processing, 30 of 46 (65%) heart sounds were proven interpretable. Atrial fibrillation and diastolic murmur were significantly associated with failure to acquire interpretable heart sounds. The diagnostic algorithm classified the heart sounds into the correct category with high accuracy: Galaxy S5, 90% (95% CI 73%-98%); Galaxy S6, 87% (95% CI 69%-96%); and LG G3, 90% (95% CI 73%-98%). Sensitivity, specificity, positive predictive value, and negative predictive value were also acceptable for the 3 devices.

   CONCLUSIONS Cardiac auscultation using smartphones was feasible. Discrimination using convolutional neural networks yielded high diagnostic accuracy. However, using the built-in microphones alone, the acquisition of reproducible and interpretable heart sounds was still a major challenge.

   TRIAL REGISTRATION ClinicalTrials.gov NCT03273803; https://clinicaltrials.gov/ct2/show/NCT03273803 (Archived by WebCite at http://www.webcitation.org/6x6g1fHIu).

   PubMed IF 6.3 순환기내과
4. 24852018

   제1저자 김지현 · 교신저자 김주성

   Kim JH, Kim J, Chun J, Lee C, Im JP, Kim JS

   Role of iRhom2 in intestinal ischemia-reperfusion-mediated acute lung injury.

   Sci Rep. 2018;8(1):3797.

   Abstract

   Intestinal ischemia-reperfusion (I/R) may cause acute systemic and lung inflammation. However, the detailed mechanism of this inflammatory cascade has not been fully elucidated. Inactive rhomboid protein 2 (iRhom2) is essential for the maturation of TNF-α converting enzyme (TACE), which is required for TNF-α secretion. We evaluated the role of iRhom2 in a mouse model of intestinal I/R using iRhom2 knockout (KO) and wild-type (WT) mice. Lung injury following intestinal I/R was significantly attenuated in iRhom2 KO mice compared with WT mice. After intestinal I/R, lungs from iRhom2 KO mice showed significantly lower myeloperoxidase (MPO) activity and markedly reduced cell apoptosis associated with a decreased level of active caspase 3 and decreased TUNEL staining compared with lungs from WT mice. TNF-α levels were elevated in the serum and lungs of WT mice with intestinal I/R and significantly reduced in iRhom2 KO mice with intestinal I/R. iRhom2 may play a critical role in the pathogenesis of acute lung injury (ALI) after intestinal I/R and thus may be a novel therapeutic target for ALI after intestinal I/R injury.

   PubMed IF 4.9 소화기내과
5. 24842018

   제1저자 조용숙 · 교신저자 이창훈

   Jo YS, Park S, Kim DK, Yoo CG, Lee CH

   The cutoff point of clinical chronic obstructive pulmonary disease questionnaire for more symptomatic patients.

   BMC Pulm Med. 2018;18(1):38.

   Abstract

   BACKGROUND An adequate threshold for the Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) defining more symptomatic COPD patients has not been determined. We aimed to determine the efficacy of the CCQ and the appropriate CCQ threshold for more symptomatic COPD patients.

   METHODS COPD patients aged > 40 years who smoked/had smoked ≥10 packs/year were prospectively enrolled over 1 year from three South Korean hospitals (n = 126). Correlations between the CCQ and St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), the modified Medical Round Council (mMRC) scale, lung function, and exercise capacity were evaluated. "More symptomatic patients" were those with an SGRQ score ≥ 25. Area under the receiver operating curve and classification and regression tree analyses were performed to determine the CCQ threshold equivalent to an SGRQ score ≥ 25.

   RESULTS The CCQ significantly correlated with the SGRQ, CAT, and mMRC scale (r = 0.76, 0.69, and 0.53, respectively). A CCQ cutoff of 1.4 predicted an SGRQ score of 25 better than others. A CCQ score of 1.4 was a significant determinant of an SGRQ score ≥ 25 even after adjusting for potential confounders.

   CONCLUSIONS The CCQ was correlated with other symptom indicators, lung function, and exercise capacity. A CCQ cutoff of 1.4 agreed better than CCQ cutoff of 1.0, suggested by guideline, and this cutoff value may identify more symptomatic COPD patients well.

   TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02527486 . Date of registration: December 19, 2014, retrospectively registered.

   PubMed IF 3.1 호흡기내과
6. 24832018

   제1저자 박종한 · 교신저자 구본권

   Park J, Lee JM, Koo BK, Shin ES, Nam CW, Doh JH, Hwang D, Zhang J, Hu X, Wang J, Ye F, Chen S, Yang J, Chen J, Tanaka N, Yokoi H, Matsuo H, Takashima H, Shiono Y, Akasaka T

   Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement.

   J Am Heart Assoc. 2018;7(4):JAHA.117.008055.

   Abstract

   BACKGROUND Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3-vessel fractional flow reserve (FFR).

   METHODS AND RESULTS A total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with "Moderate CAD" as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR>0.87 in all 3-vessels); Group 2: Single-vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR≤0.80) in any vessel. The primary end point was 2-year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Forty-three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2-year risk of major adverse cardiac events was not significantly different between patients with single-vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%-2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%-9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%-3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2-year major adverse cardiac events.

   CONCLUSIONS Global physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD.

   CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

   PubMed IF 6 순환기내과
7. 24822018

   제1저자 손경희 · 교신저자 강혜련

   Sohn KH, Kang DY, Kim JY, Lee SY, Lee KH, Han SW, Kang HR

   Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study.

   J Allergy Clin Immunol Pract. 2018;6(5):1642-1648.e2.

   Abstract

   BACKGROUND Oxaliplatin-related hypersensitivity reactions (HSRs), which can be life threatening, have introduced a dilemma regarding the use of chemotherapeutic agents. Because repeated exposure to oxaliplatin may increase the risk of sensitization, patients with a history of prior asymptomatic exposure require risk-stratified care.

   OBJECTIVE This study aimed to elucidate the incidence and risk of oxaliplatin HSRs in patients with a history of asymptomatic prior exposure.

   METHODS We performed a prospective observational study of patients who completed oxaliplatin-based chemotherapy between March 2013 and January 2015. Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity, eosinophil counts, and premedication were reviewed to assess the risk factors.

   RESULTS A total of 793 patients were enrolled, among whom 148 (18.7%) experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients but increased to 31.9% among those with a history of asymptomatic exposure and 75.0% among those with a history of oxaliplatin HSRs during the previous exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the previous HSR group, followed by the previous asymptomatic exposure and nonexposure groups. The HSR severity also differed according to the previous exposure history and HSRs. In the multivariate analysis, prior exposure to oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and a longer oxaliplatin-free interval (≥36 months; OR, 4.85; 95% CI, 1.60-14.37) were independent risk factors for HSRs.

   CONCLUSIONS Previous exposure to oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent HSR episodes, even if prior therapy was well tolerated.

   PubMed IF 6.6 알레르기내과
8. 24812018

   제1저자 박찬순,최동주 · 교신저자 박진주

   Choi DJ, Park CS, Park JJ, Lee HY, Kang SM, Yoo BS, Jeon ES, Hong SK, Shin JH, Kim MA, Park DG, Kim EJ, Hong SJ, Kim SY, Kim JJ

   Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial.

   Trials. 2018;19(1):103.

   Abstract

   BACKGROUND Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF.

   METHODS/DESIGN Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.

   DISCUSSIONS The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF.

   TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017.

   PubMed IF 2.1 순환기내과
9. 24802018

   제1저자 최기홍 · 교신저자 구본권

   Choi KH, Lee JM, Koo BK, Nam CW, Shin ES, Doh JH, Rhee TM, Hwang D, Park J, Zhang J, Kim KJ, Hu X, Wang J, Ye F, Chen S, Yang J, Chen J, Tanaka N, Yokoi H, Matsuo H, Takashima H, Shiono Y, Akasaka T

   Prognostic Implication of Functional Incomplete Revascularization and Residual Functional SYNTAX Score in Patients With Coronary Artery Disease.

   JACC Cardiovasc Interv. 2018;11(3):237-245.

   Abstract

   OBJECTIVES The aim of this study was to investigate the prognostic implication of functional incomplete revascularization (IR) and residual functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (rFSS) in comparison with 3-vessel fractional flow reserve (FFR) and residual SYNTAX score.

   BACKGROUND IR is associated with poor clinical outcomes in patients who underwent percutaneous coronary intervention.

   METHODS A total of 385 patients who underwent 3-vessel FFR measurement after stent implantation were included in this study. The rFSS was defined as residual SYNTAX score measured only in vessels with FFR ≤0.8. The study population was divided into the functional IR group (rFSS ≥1) and the functional complete revascularization (CR) group (rFSS = 0). The primary outcome was major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years.

   RESULTS Functional CR was achieved in 283 patients (73.5%). At 2-year follow-up, the functional IR group showed a significantly higher risk for MACEs (functional IR vs. CR, 14.6% vs. 4.2%; hazard ratio: 4.09; 95% confidence interval: 1.82 to 9.21; p < 0.001) than the functional CR group. In a multivariate-adjusted model, functional IR was an independent predictor of MACEs (adjusted hazard ratio: 4.17; 95% confidence interval: 1.85 to 9.44; p < 0.001). The rFSS showed a significant association with estimated 2-year MACE rate (hazard ratio: 1.09 per 1-U increase; 95% confidence interval: 1.02 to 1.17; p = 0.018). When added to clinical risk factors, rFSS showed the highest integrated discrimination improvement value for MACEs (3.5%; p = 0.002) among 3-vessel FFR, residual SYNTAX score, and rFSS.

   CONCLUSIONS Patients with functional IR showed significantly higher rate of 2-year MACEs than those with functional CR. A combined anatomic and physiological scoring system (rFSS) after stent implantation better discriminated the risk for adverse events than anatomic or physiological assessment alone. (Clinical Implication of 3-Vessel Fractional Flow Reserve [FFR]; NCT01621438).

   PubMed IF 12.7 순환기내과
10. 24792018

    제1저자 황성욱 · 교신저자 김주성

    Hwang SW, Kim JH, Lee C, Im JP, Kim JS

    Intestinal alkaline phosphatase ameliorates experimental colitis via toll-like receptor 4-dependent pathway.

    Eur J Pharmacol. 2018;820:156-166.

    Abstract

    Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme which plays an important role in gut homeostasis and mucosal inflammation. However, the mechanism of the protective effect of IAP is not fully elucidated. The aim of the present study was to evaluate whether the protective effect of IAP on colitis is mediated via the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway. For in vitro analysis, peritoneal macrophages from the wild-type (WT) and TLR4-deficient (TLR4^-/-) C57BL/6 mice were used. IAP strongly inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by suppressing the LPS-induced phosphorylation of IκBα and the DNA-binding activity of NF-κB in WT macrophages; however, the inhibitory effects mediated by IAP were reduced in the TLR4^-/- macrophages. For in vivo analysis, the protective mechanisms of IAP on dextran sulfate sodium (DSS)-induced colitis were evaluated using WT and TLR4^-/- mice. Although oral administration of IAP significantly attenuated the severity of colitis in both preventive and therapeutic models of WT mice, these protective effects were not significant in TLR4^-/- mice. When immunohistochemical analysis of IκBα was performed in the colitic tissues, the inhibitory effects of IAP on IκBα phosphorylation were also observed in the colon of WT mice, but these effects decreased in the colon of TLR4^-/- mice. In conclusion, the protective effects of IAP on colitis were mediated via the TLR4/NF-κB pathway. These results of this study shall be helpful in tailoring treatment against colitis using IAP.

    PubMed IF 5.7 소화기내과
11. 24782018

    제1저자 이근욱, 이대호 · 교신저자 방영주

    Lee KW, Lee DH, Kang JH, Park JO, Kim SH, Hong YS, Kim ST, Oh DY, Bang YJ

    Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors.

    Oncologist. 2018;23(2):155-e17.

    Abstract

    LESSONS LEARNED This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab.Nivolumab was well tolerated in Korean patients.

    BACKGROUND This phase I study of nivolumab, an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S.

    MATERIALS AND METHODS In this two-part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO-4538-13) and were followed up for 3 weeks. Those who met the required criteria proceeded to the second part (ONO-4538-14), and received the same dose as in part one every 2 weeks.

    RESULTS Six patients per dose level were enrolled (n = 18). The mean elimination half-life of nivolumab among the groups ranged from 15.0 to 19.1 days. The maximum serum concentration and area under serum concentration-time curve increased almost dose-proportionally at doses from 1 to 10 mg/kg. Adverse drug reactions (ADRs; mostly grade ≤2) were reported in seven patients (38.9%). ADRs grade ≥3 occurred in one patient (5.6%; pneumonitis). Three patients (16.7%) developed ADRs related to thyroid dysfunction.

    CONCLUSION The pharmacokinetic parameters of nivolumab were similar among patients from Korea, Japan, and the U.S. The safety profile was consistent with findings from previous studies.

    PubMed IF 4.7 혈액종양내과
12. 24772018

    제1저자 황호영, 구본권 · 교신저자 김기봉

    Hwang HY, Koo BK, Yeom SY, Kim TK, Kim KB

    Endothelial Shear Stress of the Saphenous Vein Composite Graft Based on the Internal Thoracic Artery.

    Ann Thorac Surg. 2018;105(2):564-571.

    Abstract

    BACKGROUND Endothelial shear stress (ESS) has been suggested as a factor affecting atherosclerosis and remodeling of native vessels and bypass conduits. We compared ESS levels of internal thoracic artery (ITA) and saphenous vein (SV) composite grafts intraoperatively and 1 year after coronary artery bypass grafting (CABG).

    METHODS Intraoperative ESS was calculated by measuring flow volumes and diameters of proximal and distal ITAs and SV conduits in 23 patients who received SV Y-composite grafts based on the in situ left ITA. Early (1.2 ± 0.5 days) and 1-year (12.9 ± 1.1 months) postoperative angiograms were performed in 23 and 15 patients, respectively. An intragraft Doppler-guidewire study for ESS measurement was performed in 6 patients during 1-year angiography.

    RESULTS Intraoperative diameters of proximal and distal ITAs and SV conduits were 2.0 ± 0.2 mm, 1.8 ± 0.3 mm, and 3.2 ± 0.4 mm, respectively. ESS levels were significantly different between them (41.0 ± 21.0, 28.4 ± 25.2, and 4.3 ± 3.0 dyne/cm², respectively). Proximal and distal ITA diameters increased significantly on early angiograms and remained unchanged, but SV diameter increased to 3.7 mm (95% confidence interval, 3.5 to 4.0 mm; p < 0.001) on the early angiogram and decreased to 2.9 mm (95% confidence interval, 2.7 to 3.2 mm; p < 0.001) at 1 year. Significant correlations were found between the initial ESS and proportional changes in conduit diameters during postoperative year 1. SV ESS increased in all 6 patients at 1 year, with no significant differences in ESS levels between the 3 conduits (29.9 ± 7.9, 28.8 ± 7.9, and 21.6 ± 16.3 dyne/cm², respectively).

    CONCLUSIONS Initial ESS appears to be associated with proportional changes in conduit diameters in the first year after CABG. ESS values of SV composite grafts were similar to left ITA conduits 1 year after CABG.

    PubMed IF 5.3 순환기내과
13. 24762018

    제1저자 이현정 · 교신저자 김학령

    Lee HJ, Kim HL, Chung J, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    Interaction of Metabolic Health and Obesity on Subclinical Target Organ Damage.

    Metab Syndr Relat Disord. 2018;16(1):46-53.

    Abstract

    BACKGROUND Metabolically healthy obese (MHO) individuals generally show better cardiovascular prognosis compared with metabolically unhealthy counterparts, which may be related to different patterns of target organ damage (TOD). We aimed to investigate the patterns of TOD related to obesity and metabolic unhealthiness.

    METHODS A total of 659 Korean adults (mean age, 60.0 ± 11.8 years; male, 51.1%) undergoing health examinations were stratified into four groups according to obesity (body mass index ≥25.0 kg/m²) and metabolic healthiness (meeting ≤1 criteria of metabolic syndrome excluding abdominal circumference): metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), MHO, and metabolically unhealthy obese (MUO). Four measures of TOD were evaluated: arterial stiffness, renal dysfunction, left ventricular (LV) diastolic dysfunction, and LV hypertrophy (LVH).

    RESULTS In multivariable analyses, compared with the MHNO group, the MHO group showed 2.31 times higher odds for LVH, whereas, the MUNO group showed 3.14 and 6.28 times higher odds for increased arterial stiffness and renal dysfunction, respectively. Metabolic unhealthiness was associated with increased arterial stiffness [odds ratio (OR) 2.73; confidence interval (95% CI) 1.72-4.34], renal dysfunction (OR 4.02; 95% CI 1.54-10.49), and LV diastolic dysfunction (OR 2.28; 95% CI 1.14-4.55). Meanwhile, obesity showed weaker association with LVH and LV diastolic dysfunction, and was not associated with increased arterial stiffness and renal dysfunction in multivariable analyses.

    CONCLUSIONS Metabolic unhealthiness shows more association with TOD than obesity, which may contribute to the higher risk of cardiometabolic abnormalities in MUNO compared with MHO.

    PubMed IF 1.6 순환기내과
14. 24752018

    제1저자 안창호 · 교신저자 조영민

    Ahn CH, Oh TJ, Kwak SH, Cho YM

    Sodium-glucose cotransporter-2 inhibition improves incretin sensitivity of pancreatic β-cells in people with type 2 diabetes.

    Diabetes Obes Metab. 2018;20(2):370-377.

    Abstract

    AIM To test the hypothesis that dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improves β-cell responses to incretin hormones (or β-cell incretin sensitivity) by alleviating glucose toxicity in people with type 2 diabetes mellitus (T2DM).

    METHODS A total of 19 people with T2DM underwent a 3-hour hyperglycaemic clamp study with incretin infusion before and after 8-week treatment with dapagliflozin added to the background treatment. In addition, 10 people with normal glucose tolerance (NGT) underwent a single hyperglycaemic clamp study. The hyperglycaemic clamp was targeted at 15.5 mmol/L for 3 hours, with synthetic glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) infusion over a 60- to 180-minute and a 120- to 180-minute period, respectively.

    RESULTS Compared with baseline, the C-peptide response to GLP-1 (incremental area under the curve [iAUC] of C-peptide_{60-120 minutes} ) significantly increased (83.6 ± 42.1 to 106.6 ± 45.7 nmol/L × min; P = .011), and the C-peptide response to GIP/GLP-1 (iAUC of C-peptide_{120-180 minutes} ) tended to increase after dapagliflozin treatment (82.5 ± 58.4 to 101.9 ± 50.3 nmol/L × min; P = .087), whereas both the insulin responses to GLP-1 and GIP/GLP-1 increased significantly. First-phase C-peptide response, which reflects β-cell function, significantly increased after dapagliflozin treatment; however, all these improved values in the participants with T2DM were far lower than those in the participants with NGT. In addition, the improvement in insulin responses to hyperglycaemia was correlated with the improvement in insulin responses to incretin infusion.

    CONCLUSIONS Dapagliflozin improved β-cell responses to incretin hormones as well as glucose during the hyperglycaemic clamp in patients with inadequately controlled T2DM.

    PubMed IF 6.1 내분비대사내과
15. 24742018

    제1저자 이신원, 송경호 · 교신저자 김홍빈

    Lee S, Song KH, Jung SI, Park WB, Lee SH, Kim YS, Kwak YG, Kim YK, Kiem SM, Kim HI, Kim ES, Park KH, Kim NJ, Jang HC, Kim HB, Korea INfectious Diseases (KIND) study group

    Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea.

    Clin Microbiol Infect. 2018;24(2):152-158.

    Abstract

    OBJECTIVES No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.

    METHODS A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.

    RESULTS Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.

    CONCLUSIONS Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

    PubMed IF 8.7 감염내과
16. 24732018

    제1저자 양효준 · 교신저자 김상균

    Yang HJ, Kim SG, Lim JH, Choi JM, Oh S, Park JY, Han SJ, Kim J, Chung H, Jung HC

    Surveillance strategy according to age after endoscopic resection of early gastric cancer.

    Surg Endosc. 2018;32(2):846-854.

    Abstract

    BACKGROUND Whether surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) differs in young patients is unclear. This study aimed to evaluate the risk of metachronous and extragastric recurrence in young patients with EGC after curative ESD.

    METHODS We retrospectively enrolled 1237 consecutive patients who underwent curative ESD for EGC from 2005 to 2014 at a single tertiary hospital. The patients were divided into group 1 (<50 years of age, n = 86), group 2 (age 50-74, n = 985), or group 3 (≥75 years of age, n = 166). The clinical characteristics and outcomes were compared among the three age groups.

    RESULTS Group 1 had more frequent Helicobacter pylori infection (P < 0.001), less frequent intestinal metaplasia (P = 0.021), and more frequent undifferentiated tumors (P = 0.039). Although the 5-year risk of developing metachronous recurrence appeared to be lower in group 1 (2.7%) than in groups 2 (8.6%) or 3 (8.7%), the risk became quite similar at the 7-year follow-up (6.4, 12.7, and 8.7% for groups 1, 2, and 3, respectively; P = 0.409 by log-rank test). Extragastric recurrences developed in only 2 cases in group 2 (0.2%).

    CONCLUSIONS Surveillance for metachronous and extragastric recurrence after curative ESD in patients <50 years of age should not be different from that in patients ≥50 years of age. Endoscopic surveillance for metachronous recurrence should be continued for longer than 5 years, even in young patients.

    PubMed IF 3.3 소화기내과
17. 24722018

    제1저자 고동진 · 교신저자 송영욱

    Go DJ, Shin K, Baek HJ, Kang SW, Kang YM, Jun JB, Lee YJ, Park SH, Song YW

    Pivotal factors for successful withdrawal of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis patients in remission or with low-disease activity.

    Clin Rheumatol. 2018;37(2):307-314.

    Abstract

    The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) < 3.2 who were on NSAIDs for more than a month were enrolled, and NSAIDs were discontinued. Acetaminophen (AAP) was used as the rescue medication, and NSAIDs were restarted when joint pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs. Among 109 enrolled patients, 105 completed the 16-week follow-up. Eighty-nine (84.8%) patients remained without restarting NSAIDs. In these patients, there was a slight increase in their pain levels compared with baseline (median 14.0 versus 19.0 using the pain-visual analog scale, p = 0.010). However, changes in DAS28-ESR (p = 0.638) and routine assessment of patient index data 3 (RAPID-3) (p = 0.128) were insignificant. Moreover, 66 (62.9%) patients showed sustained effectiveness on PRO without restarting NSAIDs. In the multivariate regression models, joint swelling was the detrimental factor in NSAID withdrawal (odds ratio [OR] 0.149, 95% confidence interval [CI] 0.033-0.680, p = 0.014) and sustained effectiveness (OR 0.284, 95% CI 0.091-0.883, p = 0.030). Joint pain in RA patients in remission or with LDA can be well managed without NSAIDs, especially in those without swollen joints at the time of cessation.

    PubMed IF 2.7 류마티스내과
18. 24712018

    제1저자 주세경 · 교신저자 김원

    Joo SK, Kim W, Kim D, Kim JH, Oh S, Lee KL, Chang MS, Jung YJ, So YH, Lee MS, Bae JM, Kim BG

    Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease.

    Liver Int. 2018;38(2):331-341.

    Abstract

    BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of heterogeneous metabolic subtypes. This study compared the diagnostic performances of noninvasive fibrosis tests in predicting advanced fibrosis among patients with NAFLD and examined the effects of the subgroups on their diagnostic performances.

    METHODS Three hundred fifteen patients with biopsy-proven NAFLD were prospectively enrolled. Acoustic radiation force impulse imaging (ARFI) was performed to obtain liver stiffness measurements (LSMs). The aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis 4 index (FIB-4), NAFLD fibrosis score (NFS) and BARD score were calculated. The diagnostic performances of noninvasive fibrosis tests were evaluated using the area under the receiver operating characteristic curve (AUROC).

    RESULTS Fibrosis 4 index (FIB-4) showed the highest AUROC for advanced fibrosis (0.866; 95% CI, 0.811-0.922). AUROC subgroup analyses were performed to assess the effects of the subgroups on diagnostic performance. For patients with advanced fibrosis, the APRI, BARD, FIB-4 and NFS AUROCs were significantly different among the radiological steatosis grades. Additionally, the AUROC of ARFI tended to decrease with increasing radiological steatosis severity. FIB-4 and NFS showed significantly lower AUROCs for advanced fibrosis in obese NAFLD than in nonobese NAFLD (P = .002 and P < .001 respectively). However, only radiological steatosis severity was independently associated with advanced fibrosis in multivariable analysis.

    CONCLUSIONS Steatosis severity may affect the diagnostic performances of noninvasive fibrosis tests in patients with NAFLD. The application of different tools should be tailored for various NAFLD subgroups to optimize noninvasive fibrosis assessments.

    PubMed IF 6.2 소화기내과
19. 24702018

    제1저자 박찬순 · 교신저자 최의근

    Park CS, Choi EK, Han KD, Lee HJ, Rhee TM, Lee SR, Cha MJ, Lim WH, Kang SH, Oh S

    Association between adult height, myocardial infarction, heart failure, stroke and death: a Korean nationwide population-based study.

    Int J Epidemiol. 2018;47(1):289-298.

    Abstract

    BACKGROUND The association between adult height and cardiovascular (CV) events and mortality has been suggested, albeit inconsistently. We sought to discover the comprehensive relationship between height, CV-related morbidity and all-cause death according to age.

    METHODS We investigated the association between adult height and myocardial infarction (MI), heart failure (HF), stroke incidence and mortality in 16 528 128 Korean patients who underwent regular health check-ups (2005-08). Height was stratified by decile according to age (20-39 years, 40-59 years and ≥60 years) and gender.

    RESULTS During a 9-year follow-up period, 590 346 participants died and 232 093 were admitted to hospital for MI, 201 411 for HF and 267 566 for stroke. An inverse relationship between height and MI, HF, stroke and all-cause death was observed in the overall cohort analysis. The association was unchanged after adjusting for CV risk and behavioural and adulthood socioeconomic factors. Both male and female sex showed an inverse relationship with height in adulthood, CV events and mortality. Adult height showed an inverse association in all CV events and mortality, especially in the older groups (≥40 years). In a subgroup analysis of body mass index, there was an inverse relationship between height, CV events and mortality in each group.

    CONCLUSIONS Shorter height in adulthood was strongly related to an increased risk of MI, HF, stroke and all-cause death. A suitable environment and appropriate nutrition early in life could influence adult height and eventually reduce the risk of CV events and mortality.

    PubMed IF 5.7 순환기내과
20. 24692018

    제1저자 황영재 · 교신저자 김나영

    Hwang YJ, Kim N, Lee HS, Lee JB, Choi YJ, Yoon H, Shin CM, Park YS, Lee DH

    Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years.

    Aliment Pharmacol Ther. 2018;47(3):380-390.

    Abstract

    BACKGROUND Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.

    AIM To evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long-term follow-up.

    METHODS 598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori-negative (n = 65), H. pylori non-eradicated (n = 91), and H. pylori-eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.

    RESULTS Histological follow-up was performed regularly at 1, 2, 3-4 and ≥5 years, with mean follow-up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori-eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori-eradicated and H. pylori-negative groups disappeared from 1-year follow-up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori-eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori-eradicated and H. pylori-negative groups disappeared from ≥5 years of follow-up in the antrum and from 3 years of follow-up in the corpus.

    CONCLUSION H. pylori eradication may be a preventative strategy for intestinal-type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.

    PubMed IF 6.8 소화기내과
21. 24682018

    제1저자 윤창환 · 교신저자 김효수

    Yoon CH, Kim TW, Koh SJ, Choi YE, Hur J, Kwon YW, Cho HJ, Kim HS

    Gata6 in pluripotent stem cells enhance the potential to differentiate into cardiomyocytes.

    BMB Rep. 2018;51(2):85-91.

    Abstract

    Pluripotent stem cell (PSC) variations can cause significant differences in the efficiency of cardiac differentiation. This process is unpredictable, as there is not an adequate indicator at the undifferentiated stage of the PSCs. We compared global gene expression profiles of two PSCs showing significant differences in cardiac differentiation potential. We identified 12 up-regulated genes related to heart development, and we found that 4 genes interacted with multiple genes. Among these genes, Gata6 is the only gene that was significantly induced at the early stage of differentiation of PSCs to cardiomyocytes. Gata6 knock-down in PSCs decreased the efficiency of cardiomyocyte production. In addition, we analyzed 6 mESC lines and 3 iPSC lines and confirmed that a positive correlation exists between Gata6 levels and efficiency of differentiation into cardiomyocytes. In conclusion, Gata6 could be utilized as a biomarker to select the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic purposes. [BMB Reports 2018; 51(2): 85-91].

    PubMed IF 4.1 순환기내과
22. 24672018

    제1저자 신동엽 · 교신저자 윤성수

    Shin DY, Lee JH, Park S, Lee JO, Moon JH, Ahn JS, Choi Y, Song IC, Shin HJ, Lee WS, Lee HS, Yoon SS

    Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies.

    Bone Marrow Transplant. 2018;53(2):207-212.

    Abstract

    In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

    PubMed IF 5.1 혈액종양내과
23. 24662018

    제1저자 양효준 · 교신저자 김상균

    Yang HJ, Kim SG, Lim JH, Choi JM, Oh S, Park JY, Han SJ, Kim J, Chung H, Jung HC

    Novel risk stratification for metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer.

    Gastrointest Endosc. 2018;87(2):419-428.e3.

    Abstract

    BACKGROUND AND AIMS This study stratified the risk of developing metachronous gastric cancer (MGC) after curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) to enable customization of endoscopic surveillance for MGC.

    METHODS A total of 1115 patients who underwent curative ESD based on the expanded criteria for differentiated EGC from 2005 to 2014 at a single tertiary hospital were enrolled in this retrospective cohort study. They were followed up with annual endoscopy for a median of 50.1 months. Helicobacter pylori and histologic intestinal metaplasia (IM) were evaluated. The Kaplan-Meier method and Cox regression analysis were used for risk stratification.

    RESULTS Three risk groups were identified: group 1 comprised patients with a synchronous neoplasm; group 2 comprised male patients with corpus IM; and group 3 comprised male patients without corpus IM or female patients. The 5- and 7-year cumulative risks (95% confidence interval [CI]) for metachronous recurrence were 15.1% (95% CI, 7.7-22.5) and 26.1% (95% CI, 14.9-37.3), respectively, in group 1; 5.6% (95% CI, 3.1-8.1) and 9.3% (95% CI, 5.4-13.2), respectively, in group 2; and 3.8% (95% CI, 1.6-6.0) and 4.9% (95% CI, 2.4-7.4), respectively, in group 3 (P < .001 by log-rank test). The incidence of MGCs increased constantly even after 5 years in groups 1 and 2 but not in group 3. There was not enough evidence to show an association between H pylori eradication and metachronous recurrence in the data.

    CONCLUSIONS Meticulous annual endoscopic surveillance for MGC for more than 5 years is recommended for patients with synchronous neoplasm. Endoscopic surveillance may also be extended beyond 5 years in male patients with corpus IM.

    PubMed IF 8 소화기내과
24. 24652018

    제1저자 오국환 · 교신저자 나기영

    Oh KH, Baek SH, Joo KW, Kim DK, Kim YS, Kim S, Oh YK, Han BG, Chang JH, Chung W, Na KY, Control of fluid balance guided by body composition monitoring in patients on peritoneal dialysis (COMPASS) study

    Does Routine Bioimpedance-Guided Fluid Management Provide Additional Benefit to Non-Anuric Peritoneal Dialysis Patients? Results from COMPASS Clinical Trial.

    Perit Dial Int. 2018;38(2):131-138.

    Abstract

    INTRODUCTION In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients.

    SUBJECTS AND METHODS This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262). Non-anuric (urine volume > 500 mL/day) subjects on PD were enrolled. Subjects in the control group received fluid management based on the clinical information alone. Those in the BIS group received BIS-guided fluid management along with clinical information.

    RESULTS The subjects (N = 137, mean age 51.3 ± 12.8 years, 54% male) were randomly assigned to the BIS group (n = 67) or to the control group (n = 70). There were no significant differences between the 2 groups with regard to age, sex ratio, cause of kidney failure, duration of PD, baseline comorbidity, RRF, PD method, or peritoneal transport type. At baseline, the 2 groups were not different in terms of RRF (glomerular filtration rate [GFR], 5.1 ± 2.9 vs 5.5 ± 3.7 mL/min/1.73 m²). After follow-up, changes in the GFR between the 2 groups were not different (-1.5 ± 2.4 vs -1.3 ± 2.6 mL/min/1.73 m², p = 0.593). Over the 1-year study period, both groups maintained stability of various fluid status parameters. Between the 2 groups, there were no differences in the net change of various fluid status parameters such as overhydration (OH) and extracellular water/total body water (ECW/TBW). A net change in ECW over 1 year was slightly but significantly higher in the control group (net increase, 0.57 ± 1.27 vs 0.05 ± 1.63 L, p = 0.047). However, this difference was not translated into an improvement in RRF in the BIS group. There were no differences in echocardiographic parameters or arterial stiffness at the end of follow-up.

    CONCLUSION Routine BIS-guided fluid management in non-anuric PD patients did not provide additional benefit in volume control, RRF preservation, or cardiovascular (CV) parameters. However, our study cannot be generalized to the whole PD population. Further research is warranted in order to investigate the subpopulation of PD patients who may benefit from routine BIS-guided fluid management.

    PubMed IF 1.8 신장내과
25. 24642018

    제1저자 이성우 · 교신저자 오국환

    Lee SW, Han SH, Yoo TH, Chung W, Park SK, Chae DW, Ahn C, Oh KH

    Relationship between brachial-ankle and heart-femoral pulse wave velocities and the rapid decline of kidney function.

    Sci Rep. 2018;8(1):821.

    Abstract

    The impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate (eGFR) has been inconclusive. The database of a multicenter prospective study of 2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding patients with missing baPWV (n = 257) and eGFR change (n = 180), the study included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change <-5ml/min/1.73 m²/year was defined as rapid decline. During a mean of 2.2 years, the mean eGFR change was -3.6 ml/min/1.73 m²/year, and 31.6% of patients were classified as having rapid decline. Older age, causes of CKD, increased heart rate, systolic blood pressures, and proteinuria were associated with the highest baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid decline in eGFR was 1.9 times higher in the fifth quintile than in the first quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was associated with rapid eGFR decline only when accompanied by a high hfPWV. These findings suggest that central and peripheral PWVs may simultaneously affect rapid eGFR decline.

    PubMed IF 4.9 신장내과
26. 24632018

    제1저자 이재우 · 교신저자 이상협

    Lee JW, Kim YT, Lee SH, Son JH, Kang JW, Ryu JK, Jang DK, Paik WH, Lee BS

    Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy.

    Gut Liver. 2018;12(1):102-110.

    Abstract

    BACKGROUND/AIMS To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy.

    METHODS One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates.

    RESULTS Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up.

    CONCLUSIONS CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.

    PubMed IF 4.1 소화기내과
27. 24622018

    제1저자 강지훈 · 교신저자 조영석

    Kang J, Kim YC, Park JJ, Kim S, Kang SH, Cho YJ, Yoon YE, Oh IY, Yoon CH, Suh JW, Cho YS, Youn TJ, Chae IH, Choi DJ

    Increased epicardial adipose tissue thickness is a predictor of new-onset diabetes mellitus in patients with coronary artery disease treated with high-intensity statins.

    Cardiovasc Diabetol. 2018;17(1):10.

    Abstract

    BACKGROUND Statins are widely used for lipid lowering in patients with coronary artery disease (CAD), but increasing evidence indicates an association between statin use and new-onset of diabetes mellitus (NODM). Epicardial adipose tissue (EAT) refers to the visceral fat surrounding the heart, which is associated with metabolic diseases. We sought to determine the association between EAT thickness and NODM in CAD patients treated with high-intensity statins.

    METHODS We conducted a retrospective medical record review of CAD patients treated with high-intensity statins for at least 6 months after percutaneous coronary intervention performed between January 2009 and June 2013 at Seoul National University Bundang Hospital. EAT thickness was measured by echocardiography using standardized methods.

    RESULTS A total of 321 patients were enrolled, who received high-intensity statins for a mean of 952 days; atorvastatin 40 mg in 204 patients (63.6%), atorvastatin 80 mg in 57 patients (17.8%), and rosuvastatin 20 mg in 60 patients (18.7%). During the follow-up period of 3.9 ± 1.7 years, NODM occurred in 40 patients (12.5%). On Cox proportional-hazard regression analysis, EAT thickness at systole [for each 1 mm: hazard ratio (HR) 1.580; 95% confidence interval (CI) 1.346-1.854; P < 0.001] and prediabetes at baseline (HR 4.321; 95% CI 1.998-9.349; P < 0.001) were the only independent predictors of NODM. Using binary cutoff values derived from the receiver operating characteristic curve analysis, EAT thickness at systole larger than 5.0 mm had an HR of 3.402 (95% CI 1.751-6.611, P < 0.001), sensitivity of 52.5%, and specificity of 80.8% for predicting NODM. Also, patients with EAT thickness ≥ 5 mm and prediabetes at baseline had a 12.0-times higher risk of developing NODM compared to the risk noted in patients with EAT thickness < 5 mm and normal glucose tolerance at baseline.

    CONCLUSION Epicardial adipose tissue thickness at systole is a consistent independent predictor of NODM in patients with CAD treated with high-intensity statins. Such predictors may help physicians plan adequate surveillance for early detection of NODM.

    PubMed IF 15.6 순환기내과
28. 24612018

    제1저자 조재영 · 교신저자 이창훈

    Cho J, Choi SM, Lee J, Park YS, Lee SM, Yoo CG, Kim YW, Han SK, Lee CH

    Clinical Outcome of Eosinophilic Airway Inflammation in Chronic Airway Diseases Including Nonasthmatic Eosinophilic Bronchitis.

    Sci Rep. 2018;8(1):146.

    Abstract

    We enrolled patients with confirmed sputum eosinophilia who had visited our tertiary referral hospital between 2012 and 2015. We evaluated the incidence and predictors of exacerbations in patients with nonasthmatic eosinophilic bronchitis (NAEB), and investigated predictors of improvement in eosinophilic inflammation in chronic airway diseases with or without persistent airflow limitation. In total, 398 patients with sputum eosinophilia were enrolled. Of these, 152 (38.2%) had NAEB. The incidence rate of exacerbations requiring treatment with antibiotics, systemic corticosteroids, or hospital admission was 0.13 per patient-year (95% CI, 0.06-0.19) in NAEB. Inhaled corticosteroid (ICS) did not affect the risk of exacerbations, even in an analysis of propensity score. One hundred seventy-six patients had chronic airway diseases; in 37 of these (21.0%), sputum eosinophilia had improved at the 1-year follow-up. Patients who had persistent airflow limitation were less likely to show an improvement in eosinophilic inflammation (aOR, 0.26; 95% CI, 0.09-0.77) when they were treated with ICSs for less than 75% of the follow-up days. Exacerbations requiring systemic corticosteroids, antibiotics, or hospitalization did occur, although infrequently, in NAEB patients. Among patients with chronic airway diseases, those with persistent airflow limitation were less likely to show an improvement in eosinophilic airway inflammation.

    PubMed IF 4.9 호흡기내과
29. 24602018

    제1저자 박종한 · 교신저자 김효수

    Park J, Hwang I, Kim SJ, Youn SW, Hur J, Kim HS

    Atorvastatin prevents endothelial dysfunction in high glucose condition through Skp2-mediated degradation of FOXO1 and ICAM-1.

    Biochem Biophys Res Commun. 2018;495(2):2050-2057.

    Abstract

    OBJECTIVE The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin has been reported to exert vasculo-protective action in diabetes. We investigated the vasculo-protective mechanism of atorvastatin by evaluating its effect on two major pathogenic molecules, FOXO1 and ICAM1, mediated by S-phase kinase-associated protein 2 (Skp2) in diabetic endothelial dysfunction. APPROACH AND RESULTS: [1] FOXO1: Hyperglycemic condition increased FOXO1 protein level in endothelial cells, which was reversed by atorvastatin. This atorvastatin effect was obliterated by treatment of protease inhibitor, suggesting that atorvastatin induces degradation of FOXO1. Immunoprecipitation showed that atorvastatin facilitated the binding of Skp2 to FOXO1, leading to ubiquitination and degradation of FOXO1. [2] ICAM-1: Increased ICAM1 in high glucose condition was reduced by atorvastatin. But this effect of atorvastatin was obliterated when Skp2 was inhibited, suggesting that atorvastatin enhances binding of Skp2 to ICAM1 leading to degradation. Actually, ubiquitination and degradation of ICAM-1 were reduced when Skp2 was inhibited. In vitro monocyte adhesion assay revealed that atorvastatin reduced monocyte adhesion on endothelial cells in high glucose condition, which was reversed by Skp2 knock-down.

    CONCLUSION Atorvastatin strengthens Skp2 binding to FOXO1 or ICAM1, leading to ubiquitination and degradation. Skp2-dependent ubiquitination of major pathogenic molecules is the key mechanism for statin's protective effect on endothelial function in diabetes.

    PubMed IF 2.5 순환기내과
30. 24592018

    제1저자 이충섭 · 교신저자 김진욱

    Lee CS, Jung YJ, Kim SS, Cheong JY, Lee GR, Kim HG, Kim BH, Chung JW, Jang ES, Jeong SH, Lee KH, Kim JW

    Liver volume-based prediction model stratifies risks for hepatocellular carcinoma in chronic hepatitis B patients on surveillance.

    PLoS One. 2018;13(1):e0190261.

    Abstract

    BACKGROUND AND AIM The aim of this study was to determine whether dynamic computed tomography (CT)-measured liver volume predicts the risk of hepatocellular carcinoma (HCC) when the CT scans do not reveal evidence of HCC in chronic hepatitis B (CHB) patients on surveillance.

    METHODS This retrospective multicentre cohort study included 1,246 patients who received entecavir and regular HCC surveillance in three tertiary referral centres in South Korea. Liver volumes were measured on portal venous phase CT images. A nomogram was developed based on Cox independent predictors and externally validated. Time-dependent receiver operating characteristic (ROC) analysis was performed for comparison with previous prediction models.

    RESULTS Patients who received dynamic CT studies during surveillance had significantly higher risk for HCC compared to patients without CT studies (hazard ratio [HR] = 3.1; p < 0.001). Expected/measured liver volume ratio was an independent predictor of HCC (HR = 4.2; p = 0.002) in addition to age, sex and cirrhosis. The nomogram based on the four predictors discriminated risks for HCC (HR = 4.1 and 6.0 in derivation and validation cohort, respectively, for volume score > 150; p < 0.001). Time-dependent ROC analysis confirmed better performance of the volume score compared to HCC prediction models with conventional predictors (integrated area under curve = 0.758 vs. 0.661-0.712; p < 0.05).

    CONCLUSIONS CT-measured liver volume is an independent predictor of future HCC, and nomogram-based liver volume score may stratify the risks of HCC in CHB patients who showed negative CT findings for HCC during surveillance.

    PubMed IF 2.8 소화기내과

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