SCI 발표논문

2018년 245편

1252018

제1저자 김나영, 강민정 · 교신저자 이상협

, , , , , , ,
Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells.
Anticancer Res. 2018;38(6):3527-3533.

Abstract
BACKGROUND Pancreatic cancer is a highly lethal malignancy with a poor prognosis. This study was set up to investigate the combined effect of gemcitabine and fisetin, a natural flavonoid from plants, on human pancreatic cancer cells. Meterials and Methods: Cytotoxic effect of fisetin in combination with gemcitabine on MiaPaca-2 cells was evaluated by the MTT assay, caspase 3/7 assay and propidium iodide/Annexin V. Extracellular signal-regulated kinase (ERK)-v-myc avian myelocytomatosis viral oncogene homolog (MYC) pathway was investigated by western blotting and quantitative real-time polymerase chain reaction.
RESULTS Combination treatment with fisetin and gemcitabine inhibited the proliferation of pancreatic cancer cells within 72 h and induced apoptosis, as indicated by activation of caspase 3/7. Fisetin down-regulated ERK at the protein and mRNA levels, and reduced ERK-induced MYC instability at the protein level.
CONCLUSION Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling. These results suggest that the combination of fisetin and gemcitabine could be developed as a novel potent therapeutic.
PubMed IF 1.8 소화기내과
1242018

제1저자 김휘영,남준열 · 교신저자 이정훈

, , , , , , , , , , , , ,
Intensity of surveillance for hepatocellular carcinoma determines survival in patients at risk in a hepatitis B-endemic area.
Aliment Pharmacol Ther. 2018;47(11):1490-1501.

Abstract
BACKGROUND Data are insufficient regarding the survival benefit of surveillance for hepatocellular carcinoma (HCC).
AIM To investigate the effectiveness of HCC surveillance in a hepatitis B-endemic population.
METHODS This retrospective cohort study included 1402 consecutive patients who were newly diagnosed with HCC between 2005 and 2012 at a single tertiary hospital in Korea. The primary endpoint was overall survival. Lead-time and length-time biases were adjusted (sojourn time = 140 days) and sensitivity analyses were performed.
RESULTS The most common aetiology was hepatitis B (80.4%). Cirrhosis was present in 78.2%. HCC was diagnosed during regular surveillance (defined as mean interval of ultrasonography <8 months, n = 834), irregular surveillance (n = 104) or nonsurveillance (n = 464). Patients in the regular surveillance group were diagnosed at earlier stages ([very] early stage, 64.4%) than the irregular surveillance (40.4%) or nonsurveillance (26.9%) groups and had more chance for curative treatments (52.4%) than the irregular surveillance (39.4%) or nonsurveillance (23.3%) groups (all P < 0.001). Mortality risk was significantly lower in the regular surveillance group (adjusted hazard ratio [aHR], 0.69; 95% [CI], 0.57-0.83) but not in the irregular surveillance group (aHR, 0.94; 95% CI, 0.69-1.28) compared with the nonsurveillance group after adjusting for confounding factors and lead-time. When the subjects were restricted to cirrhotic patients or Child-Pugh class A/B patients, similar results were obtained for mortality risk reduction between groups.
CONCLUSIONS HCC surveillance was associated with longer survival owing to earlier diagnosis and curative treatment. Survival advantage was significant with regular surveillance but not with irregular surveillance.
PubMed IF 6.8 소화기내과
1232018

제1저자 황인창, 김주영 · 교신저자 김효수

, , , , , , , , , ,
Therapeutic Potential of a Novel Necrosis Inhibitor, 7-Amino-Indole, in Myocardial Ischemia-Reperfusion Injury.
Hypertension. 2018;71(6):1143-1155.

Abstract
Opening of mitochondrial permeability transition pore and Ca²⁺ overload are main contributors to myocardial ischemia-reperfusion injury, which paradoxically causes a wide variety of myocardial damage. We investigated the protective role of a novel necrosis inhibitor (NecroX-7; NecX) against myocardial ischemia-reperfusion injury using in vitro and in vivo models. H9C2 rat cardiomyoblasts and neonatal cardiomyocytes were exposed to hypoxia-reoxygenation stress after pre-treatment with NecX, vitamin C, a combination of vitamin C and E, N-acetylcysteine, an apoptosis inhibitor (Z-VAD-fmk), or cyclosporine A. The main mechanism of cell death after hypoxia-reoxygenation stress was not apoptosis but necrosis, which was prevented by NecX. Protective effect of NecX was based on its potent reactive oxygen species scavenging activity, especially on mitochondrial reactive oxygen species. NecX preserved mitochondrial membrane potential through prevention of Ca²⁺ influx and inhibition of mitochondrial permeability transition pore opening, which was more potent than that by cyclosporine A. Using Sprague-Dawley rats exposed to myocardial ischemia for 45 minutes followed by reperfusion, we compared therapeutic efficacies of NecX with cyclosporine A, vitamin C, a combination of vitamin C and E, and 5% dextrose, each administered 5 minutes before reperfusion. NecX markedly inhibited myocardial necrosis and reduced fibrotic area to a greater extent than did cyclosporine A and other treated groups. In addition, NecX preserved systolic function and prevented pathological dilatory remodeling of left ventricle. The novel necrosis inhibitor has a significant protective effect against myocardial ischemia-reperfusion injury through inhibition of mitochondrial permeability transition pore opening, indicating that it is a promising candidate for cardioprotective adjunctive measure on top of reperfusion therapy.
PubMed IF 9.8 순환기내과
1222018

제1저자 박진균 · 교신저자 이은봉

, , , , , , , ,
Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.
Ann Rheum Dis. 2018;77(6):898-904.

Abstract
OBJECTIVE To determine whether a 2-week methotrexate (MTX) discontinuation after vaccination improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA).
METHODS In this prospective randomised parallel-group multicentre study, patients with RA on stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016-2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as greater than or equal to fourfold increase of haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination against ≥2 of four vaccine strains. Secondary endpoints included seroprotection (ie, HI titre ≥1:40) rate, fold change in antibody titres.
RESULTS The modified intention-to-treat population included 156 patients in the MTX-continue group and 160 patients in the MTX-hold group. More patients in MTX-hold group achieved satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, p<0.001). Seroprotection rate was higher in the MTX-hold group than the MTX-continue group for all four antigens (H1N1: difference 10.7%, 95% CI 2.0% to 19.3%; H3N2: difference 15.9%, 95% CI 5.9% to 26.0%; B-Yamagata: difference13.7%, 95% CI 5.2% to 22.4%; B-Victoria: difference 14.7%, 95% CI 4.5% to 25.0%). The MTX-hold group showed higher fold increase in their antibody titres against all four influenza antigens (all p<0.05). Change in disease activity was similar between groups.
CONCLUSIONS A temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in patients with RA without increasing RA disease activity.
TRIAL REGISTRATION NCT02897011.
PubMed IF 24 류마티스내과
1212018

제1저자 이태민, 이주명 · 교신저자 김효수

, , , , , , , , , , , , ,
Impact of Optimized Procedure-Related Factors in Drug-Eluting Balloon Angioplasty for Treatment of In-Stent Restenosis.
JACC Cardiovasc Interv. 2018;11(10):969-978.

Abstract
OBJECTIVES The aim of this study was to investigate the impact of optimizing procedure-related factors during drug-eluting balloon (DEB) angioplasty on clinical outcomes of drug-eluting stent in-stent restenosis (ISR).
BACKGROUND Although DEB angioplasty is recommended as a reasonable option for ISR, recurrent target lesion failure (TLF) still occurs in many patients after DEB angioplasty.
METHODS Consecutive patients with drug-eluting stent ISR treated with DEB (SeQuent Please) were collected from 4 centers in Korea. The primary outcome was 2-year TLF. Procedure-related modifiable independent predictors for TLF and their best cutoff values were determined.
RESULTS In a total of 256 patients (309 lesions), TLF occurred in 52 patients (20.3%). Modifiable independent predictors of TLF among procedure-related factors were residual diameter stenosis after lesion preparation (residual percentage diameter stenosis [%DS]), DEB-to-stent ratio (BSR), and DEB inflation time (T_inflation), whose best cutoff values were 20%, 0.91, and 60 s, respectively. TLF rates were significantly higher in groups with residual %DS ≥20% (34.7% vs. 12.5%; adjusted hazard ratio: 2.15; 95% confidence interval: 1.86 to 2.48; p < 0.001), BSR ≤0.91 (46.4% vs. 21.9%; adjusted hazard ratio: 2.02; 95% confidence interval: 1.75 to 2.34; p < 0.001), and T_inflation ≤60 s (26.2% vs. 14.0%; adjusted hazard ratio: 1.82; 95% confidence interval: 1.36 to 2.45; p < 0.001). When classifying ISR lesions by combination of procedure-related factors, TLF occurred in 8.3% in the fully optimized procedure group (residual %DS <20%, BSR >0.91, and T_inflation >60 s) and 66.7% in the nonoptimized group (residual %DS ≥20%, BSR ≤0.91, and T_inflation ≤60 s) (p < 0.001).
CONCLUSIONS Residual %DS after lesion preparation, BSR, and T_inflation were the only modifiable procedure-related factors in DEB angioplasty. Fully optimized DEB angioplasty with optimal lesion preparation, prolonged inflation, and sufficient dilation may play an important role in reducing TLF after DEB angioplasty.
PubMed IF 12.7 순환기내과
1202018

제1저자 박경우, 이태민 · 교신저자 김효수

, , , , , , , , , , , , ,
Randomized Prospective Comparison of Everolimus-Eluting vs. Sirolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention - 3-Year Clinical Outcomes of the EXCELLENT Randomized Trial.
Circ J. 2018;82(6):1566-1574.

Abstract
BACKGROUND Everolimus-eluting stents (EES) have equivalent short-term angiographic and clinical outcomes to sirolimus-eluting stents (SES), but EES may be superior to SES with regard to long-term clinical safety. We report the 3-year clinical outcomes of EES and SES from the prospective EXCELLENT Randomized Trial (NCT00698607).
METHODS AND RESULTS We randomly assigned 1,443 patients undergoing percutaneous coronary intervention 3:1 to receive EES and SES, respectively. We investigated endpoints including target lesion failure (TLF) and individual clinical outcomes including stent thrombosis (ST) at 3 years. For EES and SES, the TLF rate was 4.82% and 4.12% (risk ratio [RR], 1.16, 95% CI: 0.65-2.06, P=0.62), respectively. Results were similar in other efficacy endpoints including target lesion revascularization. For safety endpoints, rate of all-cause death was significantly lower for EES (1.67%) than SES (3.57%; RR, 0.46; 95% CI: 0.23-0.94, P=0.03), while the incidence of cardiac death or myocardial infarction was numerically lower in EES. On 1-year landmark analysis, rates of all-cause death and major adverse cardiovascular events were significantly lower for EES than SES. Definite or probable ST was numerically 3-fold higher for SES (1.37%) compared with EES (0.46%).
CONCLUSIONS EES and SES had similar efficacy with regard to 3-year outcomes in the EXCELLENT trial, while delayed safety events all trended to favor EES.
PubMed IF 5.8 순환기내과
1192018

제1저자 최윤진 · 교신저자 이동호

, , , , , , ,
Correction: The relationship between drinking alcohol and esophageal, gastric or colorectal cancer: A nationwide population-based cohort study of South Korea.
PLoS One. 2018;13(5):e0197765.

Abstract
[This corrects the article DOI: 10.1371/journal.pone.0185778.].
PubMed IF 2.8 소화기내과
1182018

제1저자 박준빈, 황인창 · 교신저자 김효수, 이활

, , , , , , , , , , , , , , , ,
Quantified degree of eccentricity of aortic valve calcification predicts risk of paravalvular regurgitation and response to balloon post-dilation after self-expandable transcatheter aortic valve replacement.
Int J Cardiol. 2018;259:60-68.

Abstract
BACKGROUND Limited data exist regarding the impact of aortic valve calcification (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response to balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value of AVC eccentricity in predicting the risk of PVR and response to BPD in patients undergoing TAVR.
METHODS We analyzed 85 patients with severe aortic stenosis who underwent self-expandable TAVR (43 women; 77.2±7.1years). AVC was quantified as the total amount of calcification (total AVC load) and as the eccentricity of calcium (EoC) using calcium volume scoring with contrast computed tomography angiography (CTA). The EoC was defined as the maximum absolute difference in calcium volume scores between 2 adjacent sectors (bi-partition method) or between sectors based on leaflets (leaflet-based method).
RESULTS Total AVC load and bi-partition EoC, but not leaflet-based EoC, were significant predictors for the occurrence of ≥moderate PVR, and bi-partition EoC had a better predictive value than total AVC load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In multivariate analysis, bi-partition EoC was an independent predictor for the risk of ≥moderate PVR regardless of perimeter oversizing index. The greater bi-partition EoC was the only significant parameter to predict poor response to BPD (AUC=0.775, p=0.004).
CONCLUSION Pre-procedural assessment of AVC eccentricity using CTA as "bi-partition EoC" provides useful predictive information on the risk of significant PVR and response to BPD in patients undergoing TAVR with self-expandable valves.
PubMed IF 3.3 순환기내과
1172018

제1저자 박영식 · 교신저자 이창훈

, , , , , , , , , ,
Association between secondhand smoke exposure and hypertension in never smokers: a cross-sectional survey using data from Korean National Health and Nutritional Examination Survey V, 2010-2012.
BMJ Open. 2018;8(5):e021217.

Abstract
OBJECTIVES Secondhand smoke (SHS) exposure is associated with cardiovascular disease. This study aims to determine the association between SHS exposure estimated by questionnaire and hypertension in Korean never smokers.
SETTING Korean National Health and Nutrition Examination Survey (KNHANES) V was conducted from 2010 to 2012.
PARTICIPANTS We selected the never smokers aged over 20 years who answered the question about the SHS exposure.
PRIMARY AND SECONDARY MEASURES SHS exposure in both the home and work place was estimated using a self-reporting questionnaire. We investigated the association between SHS exposure and hypertension by using multivariate analysis. And we evaluated the mean systolic and diastolic blood pressure values according to SHS exposure after adjusting for possible confounding factors. All analyses were stratified by women and men.
RESULTS There were 10 532 (women 8987 and men 1545) never smokers. We divided the subjects into three groups according to the amount of SHS exposure: none-group I, <2 hour/day-group II and ≥2 hour/day-group III. Using multivariate analysis, hypertension was more commonly associated with group III than group I in women (adjusted OR 1.50, 95% CI 1.00 to 2.04, p=0.011). Adjusted mean systolic and diastolic blood pressure values in women who were not taking antihypertensive medication were significantly elevated in group III by 2.3 and 1.7 mm Hg, respectively.
CONCLUSION SHS exposure is significantly associated with hypertension in women never smokers.
PubMed IF 2.5 호흡기내과
1162018

제1저자 김민주,문신제 · 교신저자 박영주

, , , , , ,
Association between perfluoroalkyl substances exposure and thyroid function in adults: A meta-analysis.
PLoS One. 2018;13(5):e0197244.

Abstract
OBJECTIVE Many people are exposed to perfluoroalkyl substances (PFASs) because these substances are widely used as industrial products. Although epidemiological studies suggest that PFASs can disrupt thyroid hormones, the association between PFAS exposure and thyroid function remains inconclusive. Therefore, we performed a comprehensive meta-analysis to investigate the association between PFASs exposure and thyroid hormones.
METHODS We searched medical literature databases for articles on the association between PFASs-perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS)-and thyroid hormone levels in adults. Twelve articles were included in the meta-analysis, and the pooled z values were calculated with correlation or regression coefficients.
RESULTS The blood PFOS concentration was positively correlated with free T4. The pooled z value was 0.05 (95% confidence interval (CI): 0.03, 0.08). PFOS was negatively correlated with total T4 and total T3 when excluding outlier studies. In a subgroup analysis stratified by mean PFOS concentration, PFOS was observed to be positively associated with free T4 and TSH and negatively associated with total T3 in the intermediate concentration group (8-16 ng/mL). PFOA concentration was negatively correlated with total T4 (z value, -0.06; 95% CI: -0.09, -0.03) after omitting one outlier study. PFHxS also showed a negative correlation with total T4 (z value, -0.04; 95% CI: -0.07, -0.01). A subgroup analysis of pregnant women showed that there was no association between PFASs and thyroid hormones.
CONCLUSIONS Our meta-analysis suggests that PFASs are negatively associated with total T4, and their effect can be different depending on the PFAS concentration.
PubMed IF 2.8 내분비대사내과
1152018

제1저자 박진주 · 교신저자 조구영

, , ,
Global Longitudinal Strain to Predict Mortality in Patients With Acute Heart Failure.
J Am Coll Cardiol. 2018;71(18):1947-1957.

Abstract
BACKGROUND Heart failure (HF) is currently classified according to left ventricular ejection fraction (LVEF); however, the prognostic value of LVEF is controversial. Myocardial strain is a prognostic factor independently of LVEF.
OBJECTIVES The authors sought to evaluate the prognostic value of global longitudinal strain (GLS) in patients with HF.
METHODS GLS was measured in 4,172 consecutive patients with acute HF. Patients were categorized as either HF with reduced (LVEF <40%), midrange (LVEF 40% to 49%), or preserved ejection fraction (LVEF ≥50%) and were also classified as having mildly (GLS >12.6%), moderately (8.1% < GLS <12.5%), or severely (GLS ≤8.0%) reduced strain. The primary endpoint was 5-year all-cause mortality.
RESULTS Mean GLS was 10.8%, and mean LVEF was 40%. Overall, 1,740 (40.4%) patients had died at 5 years. Patients with reduced ejection fraction had slightly higher mortality than those with midrange or preserved ejection fraction (41%, 38%, and 39%, respectively; log-rank p = 0.031), whereas patients with reduced strain had significantly higher mortality (severely reduced GLS, 49%; moderately reduced GLS, 38%; mildly reduced GLS, 34%; log-rank p < 0.001). In multivariable analysis, each 1% increase in GLS was associated with a 5% decreased risk for mortality (p < 0.001). Patients with moderate (hazard ratio: 1.31; 95% confidence interval: 1.13 to 1.53) and severe GLS reductions (hazard ratio: 1.61; 95% confidence interval: 1.36 to 1.91) had higher mortality, but LVEF was not associated with mortality.
CONCLUSIONS In patients with acute HF, GLS has greater prognostic value than LVEF. Therefore, the authors suggest that GLS should be considered as the standard measurement in all patients with HF. This new concept needs validation in further studies.
PubMed IF 22.3 순환기내과
1142018

제1저자 김민주 · 교신저자 조선욱

, , , , ,
Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves' Disease.
Int J Endocrinol. 2018;2018:9863050.

Abstract
OBJECTIVES Because thyroid hormone is an important determinant of body weight and basal metabolic rate, we investigated the changes in the basal metabolic rate and body composition sequentially after treatment for Graves' disease.
METHODS A prospective cohort study was performed with six women newly diagnosed with Graves' disease. During a 52-week treatment of methimazole, body composition, resting respiratory expenditure (REE), and handgrip strength were measured consecutively.
RESULTS After methimazole treatment, body weight was initially increased (0-8 weeks), subsequently plateaued (8-24 weeks), and gradually decreased in the later period (24-52 weeks) despite the decreased food intake. The measured REE was 40% higher than the predicted REE at baseline, and it gradually decreased after treatment. REE positively correlated with thyroid hormone levels, peripheral deiodinase activity, and thyroid's secretory capacity. Body compositional analyses showed that the fat mass increased during an earlier period (4-12 weeks), while the lean mass increased significantly during the later period (26-52 weeks). Consistent with the lean mass changes, muscle strength also significantly increased during the later period.
CONCLUSIONS Treatment of Graves' disease increased body weight and fat mass transiently with decreased REE. However, long-term compositional changes moved in a beneficial direction increasing lean mass and reinforcing muscle strength, following decreasing fat percentages.
PubMed IF 2.5 내분비대사내과
1132018

제1저자 정영애, 조영진 · 교신저자 최의근, 황금숙

, , , , , ,
Lipidomic profiling reveals free fatty acid alterations in plasma from patients with atrial fibrillation.
PLoS One. 2018;13(5):e0196709.

Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is increasing worldwide. One method used to restore sinus rhythm is direct current cardioversion (DCCV). Despite the high success rate of DCCV, AF typically recurs within the first 2 weeks. However, our understanding of the pathophysiology of AF recurrence, incidence, and progression are highly limited. Lipidomic profiling was applied to identify altered lipids in plasma from patients with AF using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis. Partial least-squares discriminant analysis revealed a clear separation between AF patients and healthy controls. The levels of several lipid species, including fatty acids and phospholipids, were different between AF patients and healthy controls, indicating that oxidative stress and inflammation are associated with the pathogenesis of AF. Similar patterns were also detected between recurrent and non-recurrent AF patients. These results suggest that the elevated saturated fatty acid and reduced polyunsaturated fatty acid levels in AF patients may be associated with enhanced inflammation and that free fatty acid levels may play a crucial role in the development and progression of AF.
PubMed IF 2.8 순환기내과
1122018

제1저자 김진원 · 교신저자 김지현

, , , , , , , , , , , , , , , , , , , ,
Predicting cumulative incidence of adverse events in older patients with cancer undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG) multicentre prospective study.
Br J Cancer. 2018;118(9):1169-1175.

Abstract
BACKGROUND Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk.
METHODS Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables.
RESULTS 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0-8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups.
CONCLUSIONS This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle.
CLINICAL TRIAL ID WHO ICTRP number, KCT0001071.
PubMed IF 7.8 혈액종양내과
1112018

제1저자 강지훈 · 교신저자 구본권, Wang Jianan

, , , , , , , , , , , ,
Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR): Rationale and design of a randomized clinical trial.
Am Heart J. 2018;199:7-12.

Abstract
BACKGROUND Coronary angiography has limitations in defining the ischemia-causing stenotic lesion, especially in cases with intermediate coronary stenosis. Fractional flow reserve (FFR) is a current standard method to define the presence of ischemia, and intravascular ultrasound (IVUS) is the most commonly used invasive imaging tool that can provide the lesion geometry and can provide the information on plaque vulnerability. The primary aim of this study is to compare the safety and efficacy of FFR-guided and IVUS-guided percutaneous coronary intervention (PCI) strategies in patients with intermediate coronary stenosis.
TRIAL DESIGN Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR) trial is an international, multicenter, prospective, randomized clinical trial. A total of 1,700 consecutive patients with intermediate stenosis (40%-70% by visual estimation) in a major epicardial coronary artery will be randomized 1:1 to receive either FFR-guided or IVUS-guided PCI strategy. Patients will be treated with PCI according to the predefined criteria for revascularization; FFR ≤ 0.80 in the FFR-guided group and Minimal Lumen Area (MLA) ≤3 mm² (or 3 mm²<MLA ≤4 mm² and plaque burden >70%) in the IVUS-guided group. The primary end point is the patient-oriented composite outcome, which is a composite of all-cause death, myocardial infarction, and any repeat revascularization at 24months after randomization. We will test noninferiority of current standard FFR-guided PCI strategy compared with IVUS-guided decision for PCI and stent optimization strategy.
CONCLUSION The FLAVOUR trial will compare the safety and efficacy of FFR- and IVUS-guided PCI strategies in patients with intermediate coronary stenosis. This study will provide an insight on optimal evaluation and treatment strategy for patients with intermediate coronary stenosis.
PubMed IF 3.4 순환기내과
1102018

제1저자 남준열 · 교신저자 김윤준

, , , , , , , , ,
Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg-positive high viral load chronic hepatitis B.
J Viral Hepat. 2018;25(5):552-560.

Abstract
The treatment option in chronic hepatitis B (CHB) patients with persistent low-level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg-positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.
PubMed IF 2.3 소화기내과
1092018

제1저자 임수 · 교신저자 고광곤

, ,
Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors.
Atherosclerosis. 2018;272:33-40.

Abstract
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed. Most clinical trials with DPP4 inhibitors have shown no inferiority compared with placebo treatments in terms of CV safety. However, they did not show benefits in terms of adverse CV events or mortality. CV outcome trials with GLP1 receptor agonists showed inconsistent results: lixisenatide did not show benefits in preventing major adverse CV events. In contrast, liraglutide and semaglutide (longer acting GLP1 receptor agonists) proved to be superior in terms of alleviating CV morbidity and mortality. Two large-scale CV outcome trials with SGLT2 inhibitors showed significant results: empagliflozin proved to be superior in preventing CV and all-cause mortality, and canagliflozin proved to be superior in preventing CV mortality but not all-cause mortality. So far, controlling cardiometabolic risk factors such as hemodynamic changes and weight loss by SGLT2 inhibitors are suggested to be the main mechanisms for these results. However, the risk-benefit profile for these new drugs will need further elucidation, and more studies are warranted to reveal the possible mechanisms. It will also be important to confirm these results from other ongoing trials with SGLT2 inhibitors.
PubMed IF 7.1 내분비대사내과
1082018

제1저자 정고은, 이정훈, 이희선 · 교신저자 김동희

, , , , , , , ,
Nonalcoholic fatty liver disease and advanced fibrosis are associated with left ventricular diastolic dysfunction.
Atherosclerosis. 2018;272:137-144.

Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) may be associated with a wide spectrum of cardiac abnormalities, which share many metabolic risk factors. This study aimed to evaluate whether NAFLD is associated with left ventricular (LV) diastolic dysfunction independent of other classical risk factors.
METHODS A total of 3300 subjects (mean age, 54.1 years; 62.9% men), who underwent echocardiography and hepatic ultrasonography, were enrolled. LV diastolic dysfunction was diagnosed and graded using conventional and Doppler echocardiographic assessments. NAFLD was diagnosed by ultrasonographic findings without any evidence of significant alcohol consumption or viral hepatitis, other liver diseases, or medication provoking fatty liver. Advanced fibrosis was defined as having intermediate-high probability for advanced fibrosis using the NAFLD fibrosis score.
RESULTS The prevalence of LV diastolic dysfunction was 35.1%. NAFLD had a higher prevalence and severity of LV diastolic dysfunction. The prevalence rates of LV diastolic dysfunction were significantly increased according to the NAFLD fibrosis grade (30.4% for no-NAFLD, 35.2% for NAFLD without advanced fibrosis and 57.4% for NAFLD with advanced fibrosis, p < 0.001). Multivariable analysis showed that NAFLD was associated with a 29% increase in the risk of diastolic dysfunction compared with controls (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.07-1.60). There was significant interaction between obesity (BMI < 25 kg/m²vs. ≥ 25 kg/m²) and advanced fibrosis for LV diastolic dysfunction. A significant, incrementally increased risk of diastolic dysfunction according to the fibrosis grade was more pronounced in the non-obese population [adjusted OR (95% CI), 1.40 (1.06-1.84) for NAFLD without advanced fibrosis, 1.44 (0.95-2.17) for NAFLD with advanced fibrosis vs. no NAFLD, P for trend = 0.022] compared with the obese population (p for trend = 0.081), independent of other well-defined risk factors.
CONCLUSIONS NAFLD was associated with increased risk for LV diastolic dysfunction. In addition, an incrementally increased risk for LV diastolic dysfunction according to fibrosis grade was prominent in the non-obese population.
PubMed IF 7.1 소화기내과
1072018

제1저자 조벼리 · 교신저자 박영주,서정선

, , , , , , ,
Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid.
Thyroid. 2018;28(5):656-666.

Abstract
BACKGROUND Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions.
METHODS Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging.
RESULTS The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10^-6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10^-4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03).
CONCLUSIONS Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease.
PubMed IF 6.6 내분비대사내과
1062018

제1저자 박지명 · 교신저자 유철규

, , , , , , , ,
Histopathologic heterogeneity of acute respiratory distress syndrome revealed by surgical lung biopsy and its clinical implications.
Korean J Intern Med. 2018;33(3):532-540.

Abstract
BACKGROUND/AIMS Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance.
METHODS We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined.
RESULTS The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate.
CONCLUSIONS The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.
PubMed IF 2.2 호흡기내과
1052018

제1저자 곽민선 · 교신저자 정고은

, , , , , ,
Clinical implications of controlled attenuation parameter in a health check-up cohort.
Liver Int. 2018;38(5):915-923.

Abstract
BACKGROUND & AIMS Evaluation of the controlled attenuation parameter (CAP) is a promising noninvasive method for assessing hepatic steatosis. Despite the increasing reliability of the CAP for assessing steatosis in subjects with chronic liver disease, few studies have evaluated the CAP in asymptomatic subjects without overt liver disease. Therefore, we aimed to evaluate the usefulness of the CAP for a health check-up population.
METHODS We enrolled subjects who underwent abdominal ultrasonography (US), FibroScan (Echosens, France) and blood sampling during medical health check-ups. The CAP was measured using FibroScan, and increased CAP was defined as CAP ≥ 222 dB/m.
RESULTS A total of 1133 subjects were included; 589 subjects (52.0%) had fatty liver based on US, and 604 subjects (53.3%) had increased CAP. Increased CAP was significantly associated with metabolic abnormalities, including higher body mass index (BMI)[odds ratio (OR) = 1.33;95% confidence interval (CI),1.24-1.43; P < .001], higher alanine aminotransferase (ALT) (OR = 1.02; 95% CI, 1.01-1.04; P = .003), higher insulin (OR = 1.04; 95% CI, 1.00-1.08; P = .037), higher triglyceride (OR = 1.00; 95% CI, 1.00-1.01; P = 0.042) and older age (OR = 1.02; 95% CI, 1.00-1.03; P = .05). Furthermore, a comparison of clinical parameters among three groups (normal vs no fatty liver by US but increased CAP vs fatty liver based on US) revealed that metabolic parameters, including blood pressure, BMI, waist circumference, aspartate aminotransferase (AST), ALT, triglycerides, fasting glucose, uric acid, insulin, homeostasis model assessment-estimated insulin resistance and liver stiffness measurements, gradually increased across the three groups (all P < .001).
CONCLUSIONS In conclusion, increased CAP could be an early indicator of fatty liver disease with metabolic abnormalities that manifests even before a sonographic fatty change appears.
PubMed IF 6.2 소화기내과
1042018

제1저자 오규철, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , ,
Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.
Clin Ther. 2018;40(5):676-691.e1.

Abstract
PURPOSE Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.
METHODS This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared.
FINDINGS A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups.
IMPLICATIONS Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.
PubMed IF 3.7 순환기내과
1032018

제1저자 정광현 · 교신저자 이상협

, , , , , , ,
Effect of submucosal injection in endoscopic papillectomy of ampullary tumor: Propensity-score matching analysis.
United European Gastroenterol J. 2018;6(4):576-585.

Abstract
BACKGROUND The role of submucosal injection (SI) in endoscopic papillectomy (EP) is controversial.
OBJECTIVE This study investigated the effects of SI before EP of ampullary tumors.
METHODS All patients who underwent initial curative EP at our institution between March 2006 and March 2014 were retrospectively recruited. The presence of residual tumor after three months, recurrence-free survival and post-procedural adverse events were compared between the SI group and non-injection (NI) group. Propensity-score matching was performed between the two groups to reduce potential selection bias and confounding.
RESULTS A total of 122 patients were included (SI: 26, NI: 96). Following propensity-score matching, 25 paired patients were selected. Residual tumor was not shown in the NI group, whereas seven (28.0%) patients in the SI group had residual tumor (p = 0.010). The recurrence-free survival of the NI group was significantly longer than that of the SI group (p = 0.036). Upon multivariate analysis, pathologic grade (p = 0.026) and SI (p = 0.033) were significantly related to recurrence-free survival. Post-procedural adverse events were not significantly different between the two groups.
CONCLUSION SI before EP of ampullary tumor was related to more frequent residual tumor and shorter recurrence-free survival and did not reduce post-procedural adverse events.
PubMed IF 6.4 소화기내과
1022018

제1저자 박준원 · 교신저자 이은봉

, , , , ,
Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids.
Ann Rheum Dis. 2018;77(5):644-649.

Abstract
OBJECTIVES To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.
METHODS The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).
RESULTS During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).
CONCLUSION TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.
PubMed IF 24 류마티스내과
1012018

제1저자 강창경 · 교신저자 박완범

, , , , , , , , ,
18F-FDG PET and histopathologic findings in a patient with severe fever with thrombocytopenia syndrome.
Ticks Tick Borne Dis. 2018;9(4):972-975.

Abstract
We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells.
PubMed IF 3.4 감염내과
1002018

제1저자 Gambacorti-passerini C · 교신저자 Gambacorti-passerini C, 김태민

, , , , , , , , , , , , , , , , ,
Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study.
Am J Hematol. 2018;93(5):607-614.

Abstract
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty-four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval [CI], 28-77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30-93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2-36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2-year progression-free survival of 63% and 67%, respectively. The most common treatment-related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK-positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long-term treatment.
PubMed IF 9.4 혈액종양내과
992018

제1저자 이경희 · 교신저자 유철규

, , , , ,
Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells.
Mol Cells. 2018;41(4):282-289.

Abstract
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase kinase-3β (GSK-3β) via the PI3K/Akt pathway. Blockade of GSK-3β inactivation by overexpression of constitutively active GSK-3β (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of GSK-3β via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.
PubMed IF 8.2 호흡기내과
982018

제1저자 정재우 · 교신저자 강혜련

, , , , , , , , , , , , , , , , , , , ,
Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.
Int Arch Allergy Immunol. 2018;176(3-4):272-279.

Abstract
BACKGROUND Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea.
METHODS Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed.
RESULTS A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far.
CONCLUSIONS The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.
PubMed IF 2.3 알레르기내과
972018

제1저자 정경연 · 교신저자 임수

, , , , , , , ,
Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia.
Circ J. 2018;82(5):1387-1395.

Abstract
BACKGROUND Quality and quantity of high-density lipoprotein cholesterol (HDL-C) may be associated with cardiovascular risk. We investigated the effect of rosuvastatin on cholesterol efflux (CE) for HDL function and vascular health.
METHODS AND RESULTS We enrolled 30 dyslipidemic patients with type 2 diabetes mellitus and 20 healthy subjects as controls. Vascular health was assessed on flow-medicated dilation (FMD), nitroglycerin-induced dilatation of the brachial artery and carotid artery intima-media thickness (cIMT). These parameters were compared between patients and controls, and between baseline and at 12 weeks of treatment with rosuvastatin 20 mg. Age and body mass index were 49.8±11.3 years and 25.8±3.7 kg/m²in the patients, and 28.8±3.2 years and 22.4±2.4 kg/m²in the controls, respectively. The biomarkers related to lipid and glucose metabolism and lipoprotein (a), high-sensitivity C-reactive protein, and cIMT were significantly higher, and CE and FMD were significantly lower in the patients than in the controls. In the patients, rosuvastatin 20 mg decreased low-density lipoprotein cholesterol by 54.1% and increased HDL-C by 4.8%. The CE increased significantly after rosuvastatin treatment (12.26±2.72% vs. 14.05±4.14%). FMD also increased, and lipoprotein (a) and cIMT decreased significantly and were associated with changes of CE.
CONCLUSIONS Rosuvastatin-induced changes in HDL function are significantly associated with cardiovascular benefit.
PubMed IF 5.8 내분비대사내과
962018

제1저자 이주명, 김현국 · 교신저자 구본권, 정명호

, , , , , , , , , , , , , ,
Influence of Local Myocardial Damage on Index of Microcirculatory Resistance and Fractional Flow Reserve in Target and Nontarget Vascular Territories in a Porcine Microvascular Injury Model.
JACC Cardiovasc Interv. 2018;11(8):717-724.

Abstract
OBJECTIVES The aim of this study was to investigate the influence of microvascular damage in one vessel territory on invasively measured physiological parameters in the other vessel, using a porcine microvascular damage model.
BACKGROUND Although fractional flow reserve (FFR)-guided decision-making for the nonculprit stenosis in patients with acute myocardial infarction has been reported to be better than angiography-guided revascularization, there have been debates regarding the influence of microvascular dysfunction on measured FFR in nonculprit vessels.
METHODS In Yorkshire swine, microvascular damage was induced with selective intracoronary injection of microspheres (100 μm × 10⁵ each) into the left anterior descending artery (LAD). Coronary stenosis was created in both the LAD and the left circumflex artery (LCx) using balloon catheters. Coronary physiological changes were assessed with index of microcirculatory resistance (IMR) and FFR at baseline and at each subsequent injection of microsphere up to a fifth dose in both the LAD and LCx. Measurements were repeated 5 times at each stage, and a total of 424 measurements were made in 12 Yorkshire swine models.
RESULTS The median area stenosis in LAD and LCx was 48.1% (interquartile range: 40.8% to 50.4%) and 47.9% (interquartile range: 31.1% to 62.9%), respectively. At baseline, FFR in the LAD was lower than that in the LCx (0.89 ± 0.01 and 0.94 ± 0.01; p < 0.001). There was no difference in the IMR (18.4 ± 5.8 U and 17.9 ± 1.2 U; p = 0.847). With repeated injections of microspheres, IMR in LAD was significantly increased, up to 77.7 ± 15.7 U (p < 0.001). Given the same stenosis, FFR in the LAD was also significantly increased, up to 0.98 ± 0.01 along with IMR increase (p < 0.001). Conversely, IMR and FFR were not changed in the LCx throughout repeated injury to the LAD territory (p = 0.105 and p = 0.286 for IMR and FFR, respectively). The increase in LAD IMR was mainly driven by the increase in hyperemic mean transit time (p < 0.001).
CONCLUSIONS In Yorkshire swine models, local microvascular damage increased both FFR and IMR in a vessel supplying target myocardial territory. However, IMR and FFR were maintained in the other vessel. These physiological results in swine support the concept that FFR measurement might provide useful information for evaluating nonculprit lesions in clinical settings involving significant acute myocardial injury.
PubMed IF 12.7 순환기내과

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