SCI 발표논문

1. 572019

   제1저자 박효은 · 교신저자 정고은

   Park HE, Lee H, Choi SY, Kwak MS, Yang JI, Yim JY, Chung GE

   Clinical significance of hepatic steatosis according to coronary plaque morphology: assessment using controlled attenuation parameter.

   J Gastroenterol. 2019;54(3):271-280.

   Abstract

   BACKGROUND Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions.

   METHODS We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams.

   RESULTS A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171).

   CONCLUSION CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention.

   PubMed IF 5.7 순환기내과
2. 562019

   제1저자 이소령, 이영수 · 교신저자 최의근, 정보영

   Lee SR^*, Lee YS^*, Park JS, Cha MJ, Kim TH, Park J, Park JK, Lee JM, Kang KW, Shim J, Uhm JS, Kim J, Kim C, Kim JB, Park HW, Joung B, Choi EK

   Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation.

   Yonsei Med J. 2019;60(3):277-284.

   Abstract

   PURPOSE Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs.

   MATERIALS AND METHODS In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations.

   RESULTS We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use.

   CONCLUSION In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

   PubMed IF 3.1 순환기내과
3. 552019

   제1저자 김휘영, 소영호 · 교신저자 김원

   Kim HY, So YH, Kim W, Ahn DW, Jung YJ, Woo H, Kim D, Kim MY, Baik SK

   Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices.

   J Hepatol. 2019;70(3):412-422.

   Abstract

   BACKGROUND & AIMS Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices.

   METHODS In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients).

   RESULTS Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; p <0.0001). The response prediction model (Model_ΔSS = 0.0490-2.8345 × ΔSS; score = (exp[Model_ΔSS])/(1 + exp[Model_ΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC] = 0.803) using 0.530 as the threshold value. The predictive performance of the Model_ΔSS in the validation set improved using the same threshold value (AUC = 0.848).

   CONCLUSION A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices.

   LAY SUMMARY Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.

   PubMed IF 40.1 소화기내과
4. 542019

   제1저자 김원, 정동재 · 교신저자 김진욱

   Kim W, Jeong D, Chung J, Lee D, Joo S, Jang ES, Choi YJ, Yoon H, Shin CM, Park YS, Jeong SH, Kim N, Lee DH, Kim JW

   Development of colorectal cancer predicts increased risk of subsequent hepatocellular carcinoma in patients with alcoholic liver disease: case-control and cohort study.

   Sci Rep. 2019;9(1):3236.

   Abstract

   Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06-3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63-18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05-13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81-195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.

   PubMed IF 4.9 소화기내과
5. 532019

   제1저자 박세훈 · 교신저자 이하정

   Park S, Baek CH, Park SK, Kang HG, Hyun HS, Park E, Han SH, Ryu DR, Kim DK, Oh KH, Joo KW, Kim YS, Moon KC, Chin HJ, Lee H

   Clinical Significance of Crescent Formation in IgA Nephropathy - a Multicenter Validation Study.

   Kidney Blood Press Res. 2019;44(1):22-32.

   Abstract

   BACKGROUND/AIMS Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN).

   METHODS We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline.

   RESULTS Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome.

   CONCLUSION The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.

   PubMed IF 2.1 신장내과
6. 522019

   제1저자 박진주 · 교신저자 최동주

   Park JJ, Park HA, Cho HJ, Lee HY, Kim KH, Yoo BS, Kang SM, Baek SH, Jeon ES, Kim JJ, Cho MC, Chae SC, Oh BH, Choi DJ

   β-Blockers and 1-Year Postdischarge Mortality for Heart Failure and Reduced Ejection Fraction and Slow Discharge Heart Rate.

   J Am Heart Assoc. 2019;8(4):e011121.

   Abstract

   Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of β-blockers may be reduced in those patients. We sought to examine the variable effect of β-blockers on clinical outcomes according to the discharge heart rate of hospitalized HF r EF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HF r EF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of β-blockers. The primary outcome was 1-year all-cause postdischarge death according to heart rate. Among 2932 patients with HF r EF , 840 (29%) had a slow heart rate and 56% received β-blockers at discharge. Patients with slow heart rates were older and had lower 1-year mortality than those with high heart rates ( P<0.001). A significant interaction between discharge heart rate and β-blocker use was observed ( P<0.001 for interaction). When stratified, only patients without a β-blocker prescription and with a high heart rate showed higher 1-year mortality. In a Cox-proportional hazards regression analysis, β-blocker prescription at discharge was associated with 24% reduced risk for 1-year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61-0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68-1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and β-blockers may have a limited effect on HF r EF and slow discharge heart rate. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01389843.

   PubMed IF 6 순환기내과
7. 512019

   제1저자 Una Amelia Yoon, 김용철 · 교신저자 이정표, 김호

   Yoon UA, Kim YC, Lee H, Kwon S, An JN, Kim DK, Kim YS, Lim CS, Lee JP, Kim H

   The impact of sunlight exposure on mortality of patients with end stage renal disease.

   Sci Rep. 2019;9(1):2230.

   Abstract

   Recent data suggest that reduced sunlight exposure is associated with increased mortality in the general population. To date, the association between sunlight exposure and mortality in dialysis patients has not been examined. Among 134,478 dialysis patients in the Korean end-stage renal disease (ESRD) cohort from 2001 to 2014, 31,291 patients were enrolled from seven metropolitan cities, and data were analyzed using bi-directional case-crossover design. We examined the association between short-term sunlight exposure and mortality in ESRD patients. We adjusted for temperature, humidity, and daily concentrations of nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone (O₃), carbon monoxide (CO), and particle matter (PM₁₀) as confounders. The characteristics of the study population included age (65.6 ± 12.26 (mean ± standard deviation [SD]) years), sex (male, 59.96%; female, 41.04%), comorbidity (diabetes, 53.58%; hypertension, 40.5%), and kidney dialysis type (hemodialysis, 73.02%; peritoneal dialysis, 26.98%). The mean ± SD follow-up time was 4.68 ± 4.37 years. The daily sunlight exposure was significantly decreased in the case group compared with the control group (P = 0.004). Sunlight exposure was associated with all-cause death overall (ORs [95% CI]: 0.99 [0.98-0.99], P = 0.042) in a fully adjusted model. Patients with diabetes (ORs [95% CI]: 0.98 [0.97-0.99], P = 0.016) or aged higher than 75 years (ORs [95% CI]; 0.97 [0.96-0.99], P = 0.020) had higher risks of mortality than patients without diabetes or aged below 75 years, respectively. These findings suggest that sunlight exposure is inversely correlated with all-cause mortality in dialysis patients.

   PubMed IF 4.9 신장내과
8. 502019

   제1저자 이정석 · 교신저자 송영욱

   Lee JS, Lee EY, Ha YJ, Kang EH, Lee YJ, Song YW

   Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease.

   Arthritis Res Ther. 2019;21(1):58.

   Abstract

   BACKGROUND Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters.

   METHODS This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100%).

   RESULTS CTD-ILD patients (n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD (n = 384) (p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) (p < 0.001) and forced vital capacity (FVC) (p < 0.001) parameters had a moderate, negative correlation with the KL-6 level.

   CONCLUSION Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity.

   PubMed IF 5.4 류마티스내과
9. 492019

   제1저자 김태형 · 교신저자 이서영

   Kim TH, Yoon SH, Hong H, Kang HR, Cho SH, Lee SY

   Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis.

   Int Arch Allergy Immunol. 2019;179(1):31-36.

   Abstract

   BACKGROUND We conducted a meta-analysis to determine a practical observation time for detecting a biphasic reaction after resolution of the initial anaphylactic reaction.

   METHODS A systematic literature search identified studies on adult patients with anaphylaxis and a subsequent biphasic reaction due to various causes that contained sufficient data to extract outcomes. The outcomes were pooled using a random-effects model.

   RESULTS Twelve studies with a total of 2,890 adult patients with anaphylaxis and 143 patients with a biphasic reaction were included. In terms of the pooled negative predictive value, 1 h of observation achieved a 95.0% negative predictive value and ≥6 h of observation provided a 97.3% negative predictive value (95% CI: 95.0-98.5). The negative predictive value for a biphasic reaction increased with a longer observation time after initial anaphylaxis, and the increasing trend slowed down from 6 h of observation time. The pooled additional incidence rates of biphasic reactions per 100 person-hours after 1- and 4-h observations were 0.45 (95% CI: 0.20-1.04) and 0.41 (95% CI: 0.19-0.87), respectively. After > 8-12 h of postanaphylactic observation, the negative predictive value reached > 98%, while the additional incidence per 100 person-hours was < 0.10.

   CONCLUSIONS An observation time of ≥6 h after resolution of an initial anaphylaxis symptom can exclude recurrence of a secondary reaction in > 95% of patients. Although longer observation periods resulted in the detection of more biphasic reactions, 6-12 h of observation time would be practical, supporting current relevant guidelines.

   PubMed IF 2.3 알레르기내과
10. 482019

    제1저자 이주명 · 교신저자 구본권

    Lee JM, Choi KH, Park J, Hwang D, Rhee TM, Kim J, Park J, Kim HY, Jung HW, Cho YK, Yoon HJ, Song YB, Hahn JY, Nam CW, Shin ES, Doh JH, Hur SH, Koo BK

    Physiological and Clinical Assessment of Resting Physiological Indexes.

    Circulation. 2019;139(7):889-900.

    Abstract

    BACKGROUND Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent ¹³N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels.

    RESULTS Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by ¹³N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels.

    CONCLUSIONS All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease.

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

    PubMed IF 41.3 순환기내과
11. 472019

    제1저자 버트허수렌 · 교신저자 오국환

    Tsogbadrakh B, Ryu H, Ju KD, Lee J, Yun S, Yu KS, Kim HJ, Ahn C, Oh KH

    AICAR, an AMPK activator, protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway.

    Biochem Biophys Res Commun. 2019;509(3):680-686.

    Abstract

    Cisplatin causes acute kidney injury (AKI) through proximal tubular injury. We investigated the protective effect of the adenosine monophosphate protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) against cisplatin-induced AKI. We investigated whether the AMP-kinase activator AICAR ameliorates cisplatin-induced AKI through the JAK/STAT/SOCS pathway. Male Sprague-Dawley (SD) rats were randomly divided into four groups: control, AICAR, cisplatin, and cisplatin + AICAR. As appropriate to their treatment group, the rats were injected with a single dose of cisplatin (7 mg/kg, i.p.). AICAR was administered to the rats at 100 mg/kg i.p. daily. Blood urea nitrogen (BUN) and serum creatinine were measured. Renal damage was analyzed in sections stained with hematoxylin and eosin (H&E). Renal tissues were also examined by immunohistochemistry and western blot for p-AMPK, Kim-1, cleaved caspase 3, and JAK/STAT/SOCS. For in vitro studies, NRK-52E normal rat kidney cells were treated with cisplatin and/or AICAR. By western blot, we confirmed the expression of p-AMPK and the JAK/STAT/SOCS pathway in NRK-52E cells. AICAR was protective against cisplatin-induced acute tubular injury by up-regulating p-AMPK expression in NRK-52E cells. Protein expression levels of JAK2/STAT1 were markedly ameliorated in NRK-52E cells by AICAR. The protective mechanism of AICAR may be associated with suppression of the JAK2/STAT1 pathway and up-regulation of SOCS1, an inhibitor of the JAK2/STAT1 pathway. The present study demonstrates the protective effects of AICAR against cisplatin-induced AKI and shows a new renoprotective mechanism through the JAK2/STAT1/SOCS1 pathway and apoptosis inhibition. This study suggests that activation of the AMPK activator AICAR might ameliorate cisplatin-induced AKI.

    PubMed IF 2.5 신장내과
12. 462019

    제1저자 방영주 · 교신저자 Ajani JA

    Bang YJ, Kang YK, Ng M, Chung HC, Wainberg ZA, Gendreau S, Chan WY, Xu N, Maslyar D, Meng R, Chau I, Ajani JA

    A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer.

    Eur J Cancer. 2019;108:17-24.

    Abstract

    BACKGROUND Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC.

    PATIENTS AND METHODS In this randomised, double-blind, placebo-controlled, multicentre, phase II trial, patients with locally advanced or metastatic GC/GEJC not amenable to curative therapy were randomised 1:1 to receive ipatasertib or placebo, plus mFOLFOX6 (modified regimen of leucovorin, bolus and infusional 5-fluorouracil [5-FU], and oxaliplatin). The co-primary end-point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in phosphatase and tensin homolog (PTEN)-low patients. Secondary end-points included PFS in patients with PI3K/Akt pathway-activated tumours; overall survival, investigator-assessed objective response rate and duration of response in the ITT population; and safety assessments.

    RESULTS In 153 enrolled patients, the median PFS (ITT) was 6.6 months (90% confidence interval [CI], 5.7-7.5) with ipatasertib/mFOLFOX6 versus 7.5 months (90% CI, 6.2-8.1) with placebo/mFOLFOX6 (hazard ratio, 1.12; 90% CI, 0.81-1.55; P = 0.56). No statistically significant PFS benefit was observed in biomarker-selected patient subgroups (PTEN-low and PI3K/Akt pathway-activated tumours) with ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6. Other secondary end-points did not favour the ipatasertib/mFOLFOX6 treatment arm. The percentages of patients with ≥1 adverse event (AE, 100% versus 98%) and grade ≥3 AEs (79% versus 74%) were similar between arms. Higher rates of AEs leading to treatment withdrawal (16% versus 6%) and serious AEs were reported in the ipatasertib arm (54% versus 43%). Thirty-nine and 29 deaths occurred in the ipatasertib and placebo arms, respectively.

    CONCLUSIONS Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed.

    TRIAL REGISTRATION ClinicalTrials.gov (NCT01896531).

    PubMed IF 7.9 혈액종양내과
13. 452019

    제1저자 최원석 · 교신저자 최의근

    Choe WS, Choi EK, Han KD, Lee EJ, Lee SR, Cha MJ, Oh S

    Association of metabolic syndrome and chronic kidney disease with atrial fibrillation: A nationwide population-based study in Korea.

    Diabetes Res Clin Pract. 2019;148:14-22.

    Abstract

    AIMS Metabolic syndrome (MetS) and chronic kidney disease (CKD) are significant risk factors for incident atrial fibrillation (AF). Few studies have reported the synergistic effect of MetS and CKD on development of AF. We investigated the individual and synergistic effects of MetS and CKD on the risk of incident AF.

    METHODS We studied a retrospective cohort comprising 22,886,663 Koreans whose data was obtained from the national health claims database established by the Korean National Health Insurance Service between 2008 and 2013. Patients were classified into a MetS and a CKD group and followed-up until 2016 for new-onset AF. A Cox proportional hazards model assessed the independent and synergistic effect of MetS and CKD on the risk of incident AF.

    RESULTS The prevalence of MetS and CKD in these patients was 27.4% and 5.4%, respectively. During a mean follow-up of 5.4 years, AF developed in 225,529 patients (1% of the total cohort). The adjusted hazard ratio (HR) for incident AF was 1.38 (95% confidence interval [CI] 1.36-1.39) for MetS, and 1.35 (95% CI 1.34-1.37) for CKD. Patients with MetS and CKD showed a higher risk of AF (HR 1.75, 95% CI 1.73-1.78) than that observed in those without MetS and CKD.

    CONCLUSIONS The combination of MetS and CKD showed a high risk of development of AF in a large-scale nationwide cohort. Further studies are warranted to determine whether pharmacological and/or lifestyle interventions can control/manage these modifiable risk factors to reduce the risk of development of AF.

    PubMed IF 4.6 순환기내과
14. 442019

    제1저자 박지석 · 교신저자 오세일

    Park J, Cha MJ, Choi YJ, Lee E, Moon I, Kwak S, Kwon S, Yang S, Lee S, Choi EK, Oh S

    Prognostic efficacy of platelet count in patients with nonvalvular atrial fibrillation.

    Heart Rhythm. 2019;16(2):197-203.

    Abstract

    BACKGROUND The prognostic efficacy of quantitative platelet activity in atrial fibrillation (AF) remains unclear.

    OBJECTIVE The purpose of this study was to evaluate the platelet count (PLT) as a prognostic indicator in patients with nonvalvular AF.

    METHODS Data on 10,978 patients with nonvalvular AF were retrieved from a prospective registry of a single medical center in Korea. Cumulative risk for stroke and bleeding events were compared between patients with normal PLT (n = 8322), mild thrombocytopenia (n = 1791), and moderate to severe thrombocytopenia (n = 865) after propensity score matching. Prediction models for stroke were derived by conventional risk factors (model 1) and by combining PLT with model 1 (model 2), and model performance was assessed by area under the receiver operator characteristics curve (AUC).

    RESULTS During the follow-up period, 7.3%, 7.0%, and 4.5% had stroke and 7.6%, 10.8%, and 17.2% had bleeding events in the normal PLT, mild, and moderate to severe thrombocytopenia groups, respectively. Compared to the normal PLT group, the moderate to severe thrombocytopenia group showed a lower risk of stroke (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.40-0.80; P = .002). A reverse relationship was found between PLT and bleeding risk (moderate to severe thrombocytopenia: HR 2.19; 95% CI 1.77-2.70; P <.001; mild thrombocytopenia: HR 1.43; 95% CI 1.18-1.73; P <.001). Compared to model 1, model 2 showed significant improvement in risk prediction (AUC 0.628 vs 0.644; P <.001).

    CONCLUSION A lower PLT was associated with a lower risk of stroke and a higher risk of bleeding events. PLT combined with conventional risk factors showed significant improvement in prediction for stroke.

    PubMed IF 7 순환기내과
15. 432019

    제1저자 김학령 · 교신저자 김명아

    Kim HL, Kim MA, Oh S, Kim M, Yoon HJ, Park SM, Shin MS, Hong KS, Shin GJ, Shim WJ

    Sex Differences in Traditional and Nontraditional Risk Factors for Obstructive Coronary Artery Disease in Stable Symptomatic Patients.

    J Womens Health (Larchmt). 2019;28(2):212-219.

    Abstract

    BACKGROUND There have been limited data on sex-specific risk factors for coronary artery disease (CAD) in patients with stable chest pain. This study was performed to investigate whether risk factors for CAD differ by sex in stable symptomatic patients.

    METHODS Data were obtained from a nation-wide registry, enrolling 1025 patients (age, 62.0 ± 11.0 years, 587 women) with chest pain who underwent elective invasive coronary angiography under the suspicion of CAD.

    RESULTS A total of 373 patients (36.4%) had obstructive CAD (≥50% stenosis) (men vs. women: 33.8% vs. 38.3%, p = 0.135). In men, univariate analyses showed that age, renal function, total cholesterol, low-density lipoprotein cholesterol, triglyceride, C-reactive protein (CRP), left ventricular (LV) systolic function, and septal annular velocity of LV (e') were significantly associated with the presence of obstructive CAD. Among these factors, a high CRP level (≥0.50 mg/dL) was an independent predictor of CAD in multivariable analysis (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.26-6.82; p = 0.012). In women, univariate analyses showed that age, waist circumference, heart rate, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol, LV systolic function, LV mass index, e' velocity, E/e', and left atrial size were significantly associated with the presence of obstructive CAD. Among these factors, lower e' velocity (<6.35 cm/s) was an independent predictor of CAD in multivariable analysis (OR, 2.38; 95% CI, 1.21-4.70; p = 0.012).

    CONCLUSIONS Among patients with stable chest pain, inflammation and LV diastolic dysfunction are independently associated with obstructive CAD in men and women, respectively.

    PubMed IF 1.8 순환기내과
16. 422019

    제1저자 김민주, 문신제 · 교신저자 박영주

    Kim MJ, Moon S, Oh BC, Jung D, Choi K, Park YJ

    Association Between Diethylhexyl Phthalate Exposure and Thyroid Function: A Meta-Analysis.

    Thyroid. 2019;29(2):183-192.

    Abstract

    BACKGROUND Diethylhexyl phthalate (DEHP) is widely used in industrial products, particularly as plasticizers and softeners. Because it is used extensively, DEHP has been detected in humans worldwide. Although epidemiological studies suggest that DEHP can disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis, evidence on the association between DEHP exposure and thyroid function remains inconclusive. Therefore, a comprehensive meta-analysis was performed to investigate the association between DEHP exposure and the HPT axis in humans.

    METHODS A literature search of the MEDLINE, EMBASE, and Web of Science databases was conducted to search for studies in which the correlation coefficient values or regression coefficient values between three major DEHP metabolites (i.e., monoethylhexyl phthalate [MEHP], mono [2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], and mono [2-ethyl-5-oxohexyl] phthalate) and thyrotropin, free thyroxine (T4), or total T4 were determined. The association between DEHPs and thyroid hormone levels were evaluated using Pearson's correlation coefficients.

    RESULTS Thirteen eligible articles were included. Urinary MEHP and MEHHP concentration was negatively correlated with total T4. Pooled correlation coefficients between MEHP/MEHHP and total T4 were -0.02 [confidence interval (CI) -0.05 to 0.00] and -0.03 [CI -0.05 to -0.01], respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate concentration was positively correlated with thyrotropin, and the pooled correlation coefficient was 0.02 [CI 0.00-0.04].

    CONCLUSIONS The findings of this meta-analysis suggest a significant association between the exposure of DEHP metabolites and the function of the HPT axis.

    PubMed IF 6.6 내분비대사내과
17. 412019

    제1저자 김원,김동희 · 교신저자 김원,김동희

    Kim D, Kim W, Joo SK, Kim JH, Harrison SA, Younossi ZM, Ahmed A

    Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty liver disease.

    Liver Int. 2019;39(2):332-341.

    Abstract

    AIMS We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non-obese and obese nonalcoholic fatty liver disease.

    METHODS A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25 kg/m² ) and non-obese (body mass index <25 kg/m² ).

    RESULTS Observations in subjects with non-obese nonalcoholic fatty liver disease were in between non-obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non-obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high-density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non-obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non-obese nonalcoholic fatty liver disease.

    CONCLUSION While there were a few phenotypic differences from obese subjects, non-obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese nonalcoholic fatty liver disease advances to more severe disease.

    PubMed IF 6.2 소화기내과
18. 402019

    제1저자 강민규 · 교신저자 강혜련

    Kang MG, Sohn KH, Kang DY, Park HK, Yang MS, Lee JY, Kang HR

    Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea.

    Yonsei Med J. 2019;60(2):208-215.

    Abstract

    PURPOSE Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea.

    MATERIALS AND METHODS We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed.

    RESULTS A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea.

    CONCLUSION The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.

    PubMed IF 3.1 알레르기내과
19. 392019

    제1저자 이승미 · 교신저자 김원,박중신

    Lee SM, Kwak SH, Koo JN, Oh IH, Kwon JE, Kim BJ, Kim SM, Kim SY, Kim GM, Joo SK, Koo BK, Shin S, Vixay C, Norwitz ER, Park CW, Jun JK, Kim W, Park JS

    Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus.

    Diabetologia. 2019;62(2):238-248.

    Abstract

    AIMS/HYPOTHESIS Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM).

    METHODS A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10-14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24-28 weeks.

    RESULTS Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM.

    CONCLUSIONS/INTERPRETATION NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.

    PubMed IF 10.4 소화기내과
20. 382019

    제1저자 신정훈, 단기순 · 교신저자 김인호, 송상훈

    Shin J, Dan K, Han D, Kim JW, Kim KK, Koh Y, Shin DY, Hong J, Yoon SS, Park S, Song SH, Kim I

    Plasma-based protein biomarkers can predict the risk of acute graft-versus-host disease and non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation.

    Blood Cells Mol Dis. 2019;74:5-12.

    Abstract

    Predictive biomarkers for acute graft-versus-host disease (aGVHD) is currently lacking. In this study, we employed an unbiased proteome profiling method to prospectively collected plasma samples from allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients to identify protein biomarkers that predict the risk of aGVHD and non-relapse mortality (NRM). In the discovery set, including five aGVHD patients and five controls, we identified seven candidate proteins. Patients with high levels of these proteins tended to exhibit a higher risk of aGVHD and NRM compared to patients with low levels in post-engraftment plasma samples from an independent validation set (n = 89). Tissue inhibitor of metalloproteinase 1, plastin-2, and regenerating islet-derived protein 3-α were selected as the most-predictive biomarkers via an exhaustive variable screening algorithm and were collectively used to develop a biomarker panel score ranging from 0 to 3. The biomarker panel score correlated significantly with aGVHD and NRM risk in univariable and multivariable Cox models. Furthermore, using the biomarker panel score in conjunction with clinical predictors significantly improved the discriminatory performance of the Cox model in predicting aGVHD and NRM risk. Our findings suggest that plasma-derived protein biomarkers can be used to predict aGVHD and NRM before the onset of clinical manifestations.

    PubMed IF 2.1 혈액종양내과
21. 372019

    제1저자 박진균 · 교신저자 Xavier Mariette

    Park JK, Lee YJ^*, Bitoun S^*, Winthrop KL, Choi Y, Lee EB, Mariette X

    Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis.

    Ann Rheum Dis. 2019;78(2):282-284.

    PubMed IF 24 류마티스내과
22. 362019

    제1저자 이현정 · 교신저자 최의근

    Lee HJ, Choi EK, Park JB, Han KD, Oh S

    Tooth Loss Predicts Myocardial Infarction, Heart Failure, Stroke, and Death.

    J Dent Res. 2019;98(2):164-170.

    Abstract

    We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 ( n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age <65 y) and those with periodontitis. In this large Korean nationwide cohort study, we found that tooth loss showed a dose-dependent association with incident MI, HF, ischemic stroke, and all-cause death and was a good predictor of cardiovascular outcome. In clinical practice, the number of missing teeth can aid physicians in discriminating patients with a higher cardiovascular risk.

    PubMed IF 6.6 순환기내과
23. 352019

    제1저자 김학령 · 교신저자 김상현

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

    Association between the level of serum soluble ST2 and invasively measured aortic pulse pressure in patients undergoing coronary angiography.

    Medicine (Baltimore). 2019;98(8):e14215.

    Abstract

    Despite the well-documented value of ST2 in heart failure and myocardial infarction, the role of ST2 in vascular biology has not yet been well defined. This study was performed to investigate the association between serum soluble ST2 (sST2) and invasively measured aortic pulse pressure (APP). A total of 167 consecutive patients with suspected coronary artery disease (CAD) (65.1 ± 9.8 years; men, 65.9%) referred for invasive coronary angiography was prospectively enrolled. APP was measured at the ascending aorta with a pig-tail catheter, and arterial blood samples for the measurement of sST2 were collected before coronary angiography. Serum sST2 levels were quantified by radioimmunoassay. Most of the patients (73.9%) had significant CAD (stenosis ≥ 50%) on coronary angiography. Patients with higher APP (≥76 mmHg) showed a significantly higher sST2 level compared to those with lower APP (<76 mmHg) (31.7 ± 13.9 ng/mL vs 26.2 ± 10.2 ng/mL, P < .001). In simple correlation analysis, there was a significant positive correlation between sST2 levels and APP (r = 0.413, P < .001). In multiple linear regression analysis, sST2 had an independent association with APP even after controlling for potential confounders (β = 0.331, P < .001). The serum sST2 level may be independently associated with invasively measured APP in patients undergoing coronary angiography. The result of this study gives insight into the role of sST2 in aortic stiffening, and suggests that the sST2 level may be a useful marker of aortic stiffness.

    PubMed IF 2 순환기내과
24. 342019

    제1저자 이서영 · 교신저자 강혜련

    Lee SY, Kang DY, Kim JY, Yoon SH, Choi YH, Lee W, Cho SH, Kang HR

    Incidence and Risk Factors of Immediate Hypersensitivity Reactions Associated With Low-Osmolar Iodinated Contrast Media: A Longitudinal Study Based on a Real-Time Monitoring System.

    J Investig Allergol Clin Immunol. 2019;29(6):444-450.

    Abstract

    OBJECTIVES We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM.

    METHODS This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS).

    RESULTS The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not.

    CONCLUSION The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM.

    PubMed IF 6.6 알레르기내과
25. 332019

    제1저자 허건 · 교신저자 윤혁

    Huh G, Yoon H, Choi YJ, Shin CM, Park YS, Kim N, Lee DH, Kim JS

    Trends in emergency department visits and hospitalization rates for inflammatory bowel disease in the era of biologics.

    PLoS One. 2019;14(1):e0210703.

    Abstract

    BACKGROUND The use of biologics in inflammatory bowel disease (IBD) has increased recently. However, studies on whether the proportion of IBD patient visits to the emergency department (ED) has decreased are scarce. We investigated the trends in IBD-related ED visits and hospitalization rates.

    METHODS Medical records of IBD-related visits to the ambulatory department (AD) and the ED of the Seoul National University Bundang Hospital in 2007, 2009, 2012, and 2014 were reviewed. Multiple-variable logistic regression analysis was used to identify significant risk factors for hospitalization.

    RESULTS The proportion of IBD patients who visited ED was 12.3% in 2007, 9.7% in 2009, 8.3% in 2012, and 6.4% in 2014 (P = 0.002). The most common chief complaints were abdominal pain (66.9%) in Crohn's disease (CD) patients and hematochezia (36.5%) in ulcerative colitis (UC) patients. The hospitalization rate following ED visits was 47.2% in CD patients and 55.6% in UC patients (P = 0.100). Multiple-variable analysis showed that significant risk factors associated with hospitalization in CD were aggressive disease behavior (odds ratio[OR] 3.54, P = 0.017) and presence of steroid exposure (OR 2.35, P = 0.047). Elevated C-reactive protein (CRP) (>0.5 mg/dL) (OR 5.40, P = 0.016) was the only risk factor associated with hospitalization in UC.

    CONCLUSIONS The proportion of ED visits decreased from 2007 to 2014; there was no significant change in hospitalization rates. Disease behavior/presence of steroid exposure and elevated CRP were associated with hospitalization among CD and UC patients who visited the ED, respectively.

    PubMed IF 2.8 소화기내과
26. 322019

    제1저자 박지석 · 교신저자 최의근

    Park J, Choi EK, Han KD, Choi YJ, Lee E, Choe W, Lee SR, Cha MJ, Lim WH, Kang J, Park KW, Oh S, Lip GYH

    Temporal trends in prevalence and antithrombotic treatment among Asians with atrial fibrillation undergoing percutaneous coronary intervention: A nationwide Korean population-based study.

    PLoS One. 2019;14(1):e0209593.

    Abstract

    BACKGROUND We investigated the recent 10-year trends in the number of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in relation to prescription patterns of antithrombotic therapy.

    METHODS We analyzed the annual prevalence of PCI and patterns of antithrombotic therapy after PCI, including antiplatelets and oral anticoagulants (vitamin K antagonists and non-vitamin K antagonist oral anticoagulants [NOACs]), in patients with AF between 2006 and 2015 by using the Korean National Health Insurance Service database. Independent factors associated with triple therapy (oral anticoagulant plus dual antiplatelet) prescription were assessed using multivariable logistic regression analysis.

    RESULTS The number of patients with AF undergoing PCI increased gradually from 2006 (n = 2,140) to 2015 (n = 3,631) (ptrend<0.001). In 2006, only 22.7% of patients received triple therapy after PCI although 96.2% of them were indicated for anticoagulation (CHA2DS2-VASc score ≥2). The prescription rate of triple therapy increased to 38.3% in 2015 (ptrend<0.001), which was mainly attributed to a recent increment of NOAC-based triple therapy from 2013 (17.5% in 2015). Previous ischemic stroke or systemic embolism, old age, hypertension, and congestive heart failure were significantly associated with a higher triple therapy prescription rate, whereas previous myocardial infarction, PCI, and peripheral arterial disease were associated with triple therapy underuse.

    CONCLUSIONS From 2006 to 2015, the number of patients with AF undergoing PCI and the prescription rate of triple therapy increased gradually with a recent increment of NOAC-based antithrombotic therapy from 2013. Previous myocardial infarction, peripheral artery disease, and PCI were associated with underuse of triple therapy.

    PubMed IF 2.8 순환기내과
27. 312019

    제1저자 문인기 · 교신저자 최의근

    Moon I, Choi EK, Jung JH, Han KD, Choi YJ, Park J, Cho JH, Lee E, Choe W, Lee SR, Cha MJ, Lim WH, Oh S

    Ankylosing spondylitis: A novel risk factor for atrial fibrillation - A nationwide population-based study.

    Int J Cardiol. 2019;275:77-82.

    Abstract

    BACKGROUND Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, associated with a number of cardiovascular diseases. We sought to investigate whether AS increases the risk of atrial fibrillation (AF) in a nationwide population-based study.

    METHODS A total of 14,129 patients newly diagnosed with AS (mean age 41.8 ± 15.3 years, 72% male) were recruited from the Korean National Health Insurance Service database between 2010 and 2014 and followed up for new onset AF. Age- and sex-matched non-AS subjects (1:5, n = 70,645) were selected and compared with the AS patients.

    RESULTS During a mean follow-up of 3.5 years, AF was newly diagnosed in 486 patients (114 patients of the AS group). The AS patients developed AF more frequently than the non-AS subjects (2.32 vs. 1.51 per 1000 person-years). In multivariate Cox regression analysis, AS was an independent risk factor for AF (Hazard ratio [HR] 1.28, 95% confidence interval [1.03-1.58]). The AS with tumor necrosis factor inhibitor (TNFi) therapy group showed higher risk for AF (HR 1.60 [1.02-2.39]). In younger patients of the AS group (patients <40 years old), the risk for AF was three times higher than patients at same age in the non-AS group. AS was an independent risk factor for AF in men, but not in women (HR 1.53 [1.18-1.95]; HR 1.42 [0.94-2.08], respectively).

    CONCLUSIONS AS was an independent risk factor for AF, especially in those under 40 years of age and those administered TNFi. It would be reasonable to screen for AF and stroke prevention in these high-risk patients.

    PubMed IF 3.3 순환기내과
28. 302019

    제1저자 이성우 · 교신저자 오국환

    Lee SW, Kim YS, Kim YH, Chung W, Park SK, Choi KH, Ahn C, Oh KH

    Dietary Protein Intake, Protein Energy Wasting, and the Progression of Chronic Kidney Disease: Analysis from the KNOW-CKD Study.

    Nutrients. 2019;11(1):nu11010121.

    Abstract

    Studies on the effect of dietary protein intake (DPI) on chronic kidney disease (CKD) progression, along with the potential hazard of protein-energy wasting (PEW), are scarce. We evaluated the association between DPI and kidney function both cross-sectionally and longitudinally, particularly emphasizing the role of PEW, in a large-scale, observational, multicenter, prospective study. We enrolled 1572 patients with non-dialysis CKD between 2011 and 2016. CKD progression was defined by a >50% estimated glomerular filtration rate (eGFR) decrease, serum creatinine doubling, or dialysis initiation. A Cox proportional hazard regression analysis was conducted. During the mean follow-up period of 41.6 months, CKD progression was observed in 296 patients. Cross-sectionally, increased DPI was significantly associated with increased eGFR. Similarly, increased DPI tertile was significantly associated with increased renal survival in a Kaplan⁻Meier curve analysis. In the multivariate Cox proportional hazard regression analysis, the statistical significance of the DPI tertile group in CKD progression was lost when PEW-related variables were added as covariates. In penalized spline curve analysis, the adjusted odds ratio of PEW significantly increased as DPI decreased. DPI, per se was not a major determinant of CKD progression. An intimate association between reduced DPI and PEW may be a more important predictor of CKD progression than DPI.

    PubMed IF 5.8 신장내과
29. 292019

    제1저자 임주현 · 교신저자 이동호

    Lim JH, Lee DH, Lee SH, Kim JS, Jung HC, Cho SH

    Asthma under control is inversely related with erosive esophagitis among healthy adults.

    PLoS One. 2019;14(1):e0210490.

    Abstract

    BACKGROUND Some recent studies suggested that reflux esophagitis is positively correlated with asthma. However, there are debates on this issue. The aim of this study is to clarify the true association between reflux esophagitis and asthma in a large population.

    METHODS Medical records of subjects who received health surveillance checkup between January 2005 and December 2011 were reviewed. Their endoscopic findings, medical history, body mass index, and smoking history were analyzed. Erosive esophagitis was defined as endoscopically detected mucosal break at the Z-line, irrespective of reflux symptom. Information about asthma history was obtained from their questionnaires and medical records.

    RESULTS Out of the total 15,999 patients, 986 had erosive esophagitis and 376 had asthma. In this population, erosive esophagitis was inversely related with asthma in univariable analysis (OR, 0.586; 95% CI, 0.342-1.003, p = 0.049). In multivariable analysis, asthma was demonstrated as an independent negative risk factor for erosive esophagitis (OR, 0.472; 95% CI, 0.257-0.869, p = 0.016), under adjustment with age (OR, 1.000; 95% CI, 0.994-1.006, p = 0.977), male sex (OR, 2.092; 95% CI, 1.683-2.601, p < 0.001), body mass index (OR, 1.115; 95% CI, 1.090-1.141, p < 0.001), smoking (OR, 1.584; 95% CI, 1.318-1.902, p < 0.001), and urban residence (OR, 1.363; 95% CI, 1.149-1.616, p < 0.001). Likewise, erosive esophagitis was shown to be an independent negative risk factor for asthma (OR, 0.558; 95% CI, 0.324-0.960, p = 0.035) under adjustment with age (OR, 1.025; 95% CI, 1.015-1.034, p <0.001), male sex (OR, 0.861; 95% CI, 0.691-1.074, p = 0.185), and body mass index (OR, 1.067; 95% CI, 1.030-1.106, p < 0.001) in multivariable analysis.

    CONCLUSIONS Contrary to previous studies, this large scale data showed inverse association between erosive esophagitis and asthma. Further studies investigating the clear mechanism of this phenomenon are warranted.

    PubMed IF 2.8 소화기내과
30. 282019

    제1저자 김률 · 교신저자 김범석

    Kim R, Keam B, Kim S, Kim M, Kim SH, Kim JW, Kim YJ, Kim TM, Jeon YK, Kim DW, Chung DH, Lee JS, Heo DS

    Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: therapeutic implications for immune checkpoint inhibitors.

    BMC Cancer. 2019;19(1):19.

    Abstract

    BACKGROUND We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway.

    METHODS Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells.

    RESULTS Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1⁺ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3⁺ (P = 0.078), CD8⁺ (P = 0.055), FOXP3⁺ (P = 0.016), and PD-1⁺ (P = 0.016) TILs.

    CONCLUSIONS There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1⁺ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti-PD-1 antibody in BM.

    PubMed IF 4.1 혈액종양내과

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