SCI 발표논문

전체 4,588편

27882019

제1저자 김효진 · 교신저자 오국환

, , , , , , , ,
Serum klotho is inversely associated with metabolic syndrome in chronic kidney disease: results from the KNOW-CKD study.
BMC Nephrol. 2019;20(1):119.

Abstract
BACKGROUND Metabolic syndrome (MS) is prevalent in chronic kidney disease (CKD). Klotho, a protein linked to aging, is closely associated with CKD. Each component of MS and klotho has an association. However, little is known about the association between klotho and MS per se. We investigated the association between serum klotho levels and MS using baseline cross-sectional data obtained from a large Korean CKD cohort.
METHODS Of the 2238 subjects recruited in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) between 2011 and 2016, 484 patients with missing data on serum klotho and extreme klotho values (values lower than the detectable range or > 6000 pg/mL) or with autosomal dominant polycystic kidney disease patients were excluded. The data of the remaining 1754 subjects were included in the present study. MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria. Serum klotho levels were measured using an enzyme-linked immunosorbent assay.
RESULTS Mean patient age was 54.9 ± 12.1 years and 1110 (63.3%) were male. The prevalence of MS among all study subjects was 63.7% (n = 1118). The median serum klotho level was 527 pg/mL (interquartile range [IQR]: 418-656 pg/mL). Serum klotho level was significantly lower in MS patients than patients without MS (Median [IQR]; 521 pg/mL [413, 651] vs. 541 pg/mL [427, 676], respectively; P = 0.012). After adjusting for age, sex, estimated glomerular filtration rate, and overt proteinuria, serum klotho was independently associated with MS (adjusted odds ratio [OR], 0.44; 95% confidence interval, 0.23-0.82; P = 0.010). Furthermore, the adjusted OR for MS was found to be significantly increased at serum klotho levels of < 518 pg/mL (receiver operating characteristic curve cut-off value).
CONCLUSIONS Serum klotho was inversely associated with the presence of MS in patients with CKD.
TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov on 26 June 2012 ( https://clinicaltrials.gov;NCT01630486 ).
PubMed IF 2.9 신장내과
27872019

제1저자 전재창 · 교신저자 윤혁

, , , , , , ,
The effect of vitamin D administration on inflammatory markers in patients with inflammatory bowel disease.
Intest Res. 2019;17(2):210-217.

Abstract
BACKGROUND/AIMS The exact relationship between vitamin D deficiency and inflammatory bowel disease (IBD) remains unclear. We evaluated the effect of vitamin D3 administration on inflammatory responses and disease severity in patients with IBD.
METHODS We investigated the serum 25-hydroxyvitamin D3 [25-(OH)D] and C-reactive protein (CRP) levels and the partial Mayo score (PMS) in patients with IBD. Vitamin D3 was administered in patients with either vitamin D deficiency or insufficiency and CRP serum vitamin D levels and PMS were re-examined at 6 months of administration.
RESULTS In 88 patients with Crohn's disease (CD), a negative correlation was found between serum vitamin D and CRP. In 178 patients with ulcerative colitis (UC), serum vitamin D showed no association with CRP or PMS. Serum vitamin D increased from 11.08±3.63 to 22.69±6.11 ng/mL in 29 patients with CD and from 11.45±4.10 to 24.20±6.61 ng/mL in 41 patients with UC who received vitamin D3 treatment (P<0.001 and P<0.001, respectively). In patients with CD, median ΔCRP was -0.24 in the normalized vitamin D group and -0.11 in the non-normalized group (P=0.308). In patients with UC, median ΔCRP was -0.01 in the normalized vitamin D group and 0.06 in the non-normalized group (P=0.359).
CONCLUSIONS Although a negative correlation was found between serum vitamin D and CRP levels in patients with CD, administration of vitamin D did not improve the CRP level in patients with CD. In patients with UC, serum vitamin D level was unrelated to CRP or PMS.
PubMed IF 4.7 소화기내과
27862019

제1저자 유덕균 · 교신저자 김윤준

, , , , , , , ,
Hepatitis B virus X protein induces size-selective membrane permeabilization through interaction with cardiolipin.
Biochim Biophys Acta Biomembr. 2019;1861(4):729-737.

Abstract
Hepatitis B virus X protein (HBx) functions in a variety of cellular events during the HBV life cycle. In a previous study, we reported that the HBx protein is sufficient to induce mitochondrial membrane permeabilization; however, the exact mechanism of HBx-induced mitochondrial membrane permeabilization has been not proposed. In this study, we report that HBx specifically targets cardiolipin (CL) and induces membrane permeabilization depending on CL concentration in mitochondrial outer membrane-mimic artificial liposomes. Interestingly, HBx-induced membrane permeabilization was enhanced by liposomes containing phosphatidylethanolamine, which plays a crucial role in forming a negative curvature on the membrane. We also show that the 68-117 region of HBx, which interacts with mitochondria, is necessary for membrane permeabilization. We examined the size of the pores formed by HBx and found that HBx permeates fluorescent dyes depending on the hydrodynamic diameter with a pore size of approximately 10 nm. The results of this study suggest that CL is necessary for HBx-induced membrane permeabilization and provide important information that suggests a new strategy for anti-HBV therapy.
PubMed IF 2.4 소화기내과
27852019

제1저자 이승표, 서재경 · 교신저자 최지은, 김용진

, , , , , , , , , , , , ,
Coronary computed tomography angiography vs. myocardial single photon emission computed tomography in patients with intermediate risk chest pain: a randomized clinical trial for cost-effectiveness comparison based on real-world cost.
Eur Heart J Cardiovasc Imaging. 2019;20(4):417-425.

Abstract
AIMS To compare the cost-effectiveness of coronary computed tomography angiography (CCTA) vs. myocardial single photon emission computed tomography (SPECT) in patients with stable intermediate risk chest pain.
METHODS AND RESULTS Non-acute patients with 10-90% pre-test probability of coronary artery disease from three high-volume centres in Korea (n = 965) were randomized 1:1 to CCTA or myocardial SPECT as the initial non-invasive imaging test. Medical costs after randomization, the downstream outcome, including all-cause death, acute coronary syndrome, cerebrovascular accident, repeat revascularization, stent thrombosis, and significant bleeding following the initial test and the quality-adjusted life-years (QALYs) gained by the EuroQoL-5D questionnaire was compared between the two groups. In all, 903 patients underwent the initially randomized study (n = 460 for CCTA, 443 for SPECT). In all, 65 patients underwent invasive coronary angiography (ICA) in the CCTA and 85 in the SPECT group, of which 4 in the CCTA and 30 in the SPECT group demonstrated no stenosis on ICA [6.2% (4/65) vs. 35.3% (30/85), P-value < 0.001]. There was no difference in the downstream clinical events. QALYs gained was higher in the SPECT group (0.938 vs. 0.955, P-value = 0.039) but below the threshold of minimal clinically important difference of 0.08. Overall cost per patient was lower in the CCTA group (USD 4514 vs. 5208, P-value = 0.043), the tendency of which was non-significantly opposite in patients with 60-90% pre-test probability (USD 5807 vs. 5659, P-value = 0.845).
CONCLUSION CCTA is associated with fewer subsequent ICA with no difference in downstream outcome. CCTA may be more cost-effective than SPECT in Korean patients with stable, intermediate risk chest pain.
PubMed IF 6.1 순환기내과
27842019

제1저자 임수 · 교신저자 임수

, ,
Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome.
Obes Rev. 2019;20(4):599-611.

Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed.
PubMed IF 7.6 내분비대사내과
27832019

제1저자 임수 · 교신저자 임수

Effects of sodium-glucose cotransporter inhibitors on cardiorenal and metabolic systems: Latest perspectives from the outcome trials.
Diabetes Obes Metab. 2019;21 Suppl 2:5-8.

Abstract
Diabetes mellitus is strongly linked to high risk of cardiovascular and renal disorders. Diabetes management requires coordinated efforts to manage multiple cardiometabolic risk factors. Diabetes mellitus is also associated with poor outcome in patients after cardiovascular events and renal complications. However, whether specific antidiabetic agents are safer and more efficacious than other drugs for preventing and treating these cardiometabolic and renal diseases is debated. To date, results are available from 12 cardiovascular outcome trials focusing mainly on major adverse cardiovascular events and renal outcomes with new antidiabetic agents (4 with dipeptidyl peptidase-4 inhibitors, 3 with sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 5 with glucagon-like peptide-1 analogues). Among them, the studies of SGLT2 inhibitors showed favourable results both for cardiovascular and renal outcomes. It would be crucial to dissect the effects of SGLT2 inhibitors on cardiorenal and metabolic systems, to determine whether it is better to prescribe SGLT2 inhibitors compared with other antidiabetic medications.
PubMed IF 6.1 내분비대사내과
27822019

제1저자 이정원 · 교신저자 김나영

, , , , , , , ,
Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.
Helicobacter. 2019;24(2):e12561.

Abstract
BACKGROUND The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection.
AIMS To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance.
METHODS Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined.
RESULTS In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies.
CONCLUSIONS Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.
PubMed IF 4.6 소화기내과
27812019

제1저자 김현숙, 고정아 · 교신저자 오윤규

, , , , , , ,
Baseline characteristics of the autosomal-dominant polycystic kidney disease sub-cohort of the KoreaN cohort study for outcomes in patients with chronic kidney disease.
Nephrology (Carlton). 2019;24(4):422-429.

Abstract
AIM The aim of this study was to describe the baseline characteristics of autosomal-dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD).
METHODS From April 2011 to February 2016, patients with CKD stage 1-5 (pre-dialysis) were enrolled as an ADPKD sub-cohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function and the factors associated with kidney function were analysed.
RESULTS A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 ± 33.3 mL/min per 1.73 m² (50.5% male with a mean age of 47.0 ± 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6 and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 years than the other age groups. Older age, a higher 24-h urine protein excretion, larger htTKV and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR.
CONCLUSION This sub-cohort will provide clinical characteristics and outcomes of Korean ADPKD patients, which can be compared with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD.
PubMed IF 2 신장내과
27802019

제1저자 송경호 · 교신저자 김의석

, , , , , , , , , , , , , , , , , , , ,
Clinical and Molecular Characterization of Panton-Valentine Leukocidin-Positive Invasive Staphylococcus aureus Infections in Korea.
Microb Drug Resist. 2019;25(3):450-456.

Abstract
AIM Panton-Valentine leukocidin (PVL) is a virulent cytotoxin and an indicator of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection. In this study, we evaluated the prevalence and clinical and molecular characteristics of PVL-positive invasive S. aureus (ISA) infections in Korea.
RESULTS A collection of 1,962 nonduplicate clinical isolates were screened for multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec), accessory gene regulator typing, major toxins, and antimicrobial susceptibility. Twenty-eight (1.4%) PVL-positive S. aureus samples were found; of them 19 (67.9%) were MRSA (8 CA and 11 healthcare-associated infections). Seventeen patients (60.7%) were men (median age: 63 years; range: 13-93 years) and 12 patients (42.9%) had no underlying comorbidities. The most common infections were skin and skin structure infection (SSSI) and pneumonia. The 30-day mortality rate was 37.0%. The most common PVL-positive MRSA clones were ST8-SCCmec IVa and ST30-SCCmec IVc along with their single-locus variants. Antimicrobial susceptibility and toxin-gene profile differed according to the clone.
CONCLUSIONS ISA infections caused by PVL-positive strains are rare in Korea, with the two most common infections being SSSI and pneumonia. Our findings indicated that several PVL-positive MRSA clones, predominantly ST8-SCCmecIVa and ST30-SCCmecIVc, were circulating and causing sporadic cases of ISA infections in the community and hospital settings.
PubMed IF 1.8 감염내과
27792019

제1저자 박흥우 · 교신저자 Tantisira KG

, , ,
Gene expression changes in lymphoblastoid cell lines and primary B cells by dexamethasone.
Pharmacogenet Genomics. 2019;29(3):58-64.

Abstract
BACKGROUND Human Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) have been thought to be a useful model system for pharmacogenomics studies. The purpose of this study was to determine the effect of Epstein-Barr virus transformation on gene expression changes by dexamethasone (Dex) in LCLs and primary B cells (PBCs) derived from the same individuals.
PATIENTS AND METHODS We prepared LCLs and purified PBCs from the same six male donors participating in the Childhood Asthma Management Program clinical trial, and compared mRNA profiles after 6 h incubation with Dex (10 mol/l) or sham buffer. We assessed differential expression and put the list of differentially expressed genes into the web interface of ConsensusPathDB to find the pathway-level interpretation of our genes specified. As a supplementary analysis, we looked at the expression of the Dex-regulated (inducing or repressing) genes in treatment-naive PBCs and LCLs (pre-Dex treatment) from the GSE30916 dataset.
RESULTS By hierarchical clustering, we found clustering of probes by cell types but not by individuals irrespective of Dex treatment. We observed that the Dex-regulated genes significantly overlapped in PBCs and LCLs. In addition, the expression of these genes showed significant correlations between treatment-naive PBCs and LCLs. Common genes showing significantly decreased expressions by the Dex treatment in both cells were enriched in immune responses and proinflammatory signaling pathways.
CONCLUSION Taken together, these results suggest the uses of LCLs are representative of the primary biologic effects of corticosteroids treatment.
PubMed IF 1.6 알레르기내과
27782019

제1저자 정완교/김경아 · 교신저자 정숙향

, , , , ,
Cost-effectiveness of sofosbuvir plus ribavirin therapy for hepatitis C virus genotype 2 infection in South Korea.
J Gastroenterol Hepatol. 2019;34(4):776-783.

Abstract
BACKGROUND AND AIM For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost-effectiveness of SOF + RBV compared with PR for treatment-naïve genotype 2 CHC in South Korea.
METHODS Using a decision analytic Markov model, a cost-effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment-naïve genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40-49, 50-59, and 60-69 years were simulated to progress through the fibrosis stages F0-F4 to end-stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health-related quality of life, costs, and transition probabilities were used.
RESULTS While the incremental cost-effectiveness ratio for PR was dominant over no treatment, the incremental cost-effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost-effective at a willingness to pay of $29 754.4 (per-capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively.
CONCLUSIONS The SOF + RBV is a cost-effective option for genotype 2 treatment-naïve CHC patients, especially for the patients with liver cirrhosis in Korea.
PubMed IF 3.5 소화기내과
27772019

제1저자 이진용/조유리 · 교신저자 김원/이국래

, , , , , , , ,
Incidence, inhospital mortality, and readmission among patients with alcoholic hepatitis in Korea: A nationwide study.
J Gastroenterol Hepatol. 2019;34(4):747-754.

Abstract
BACKGROUND AND AIM Alcoholic hepatitis (AH) ranks among the most costly diseases in South Korea. However, accurate hospitalization incidence rates, mortality rates, and contributing factors have not been investigated in South Korea. This study aimed to provide the nationwide incidence of hospitalization, inhospital mortality, and readmission rates for South Korean patients with AH.
METHODS Using the Korean Health Insurance Review and Assessment service database, a total of 39 800 inpatient cases from 2008 to 2012 were identified based on the International Classification of Diseases, 10th Revision diagnosis code for AH (K70.1). Standardized hospitalization incidence and mortality rates were calculated, and logistic regression analysis was performed to identify risk factors for inhospital mortality and readmission. Follow-up data for those admitted in 2008 were collected to assess readmissions.
RESULTS The standardized incidence rate for AH hospitalization per 10⁵ person/year decreased from 19 in 2008 to 14 in 2012 (P = 0.001). The annual inhospital mortality rate ranged from 0.2% to 0.5%. Inhospital mortality was significantly higher in older patients (odds ratio [OR], 1.36) and those with cirrhosis (OR, 4.40). The readmission rate for patients admitted in 2008 was 34.0%. Male sex (OR, 1.21) and low economic status (OR, 2.35) were significantly associated with readmission, whereas older age (OR, 0.96), cirrhosis (OR, 0.77), and urban residency (OR, 0.68) were inversely associated with readmission.
CONCLUSIONS This study captured a 5-year epidemiologic period in South Korea of patients with AH to reflect the real burden of AH and to provide valuable information to policy-makers assessing public health priorities.
PubMed IF 3.5 소화기내과
27762019

제1저자 조정현 · 교신저자 김재환, 박도현

, , , , , , , ,
Same-session endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography-based tissue sampling in suspected malignant biliary obstruction: A multicenter experience.
J Gastroenterol Hepatol. 2019;34(4):799-805.

Abstract
BACKGROUND AND AIM Few studies compared endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) with endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling in terms of diagnostic accuracy in suspected malignant biliary obstruction. We evaluated and compared the diagnostic performance of EUS-FNA and ERCP-based tissue sampling.
METHODS This multicenter study included 263 patients with suspected malignant biliary obstruction who underwent same-session EUS and ERCP between 2012 and 2016.
RESULTS Malignancies were confirmed in 239 patients (90.9%) and benign in 24 patients (9.1%). Overall diagnostic sensitivity and accuracy were 73.6% and 76.1% for EUS-FNA, 56.5% and 60.5% for ERCP, and 85.8% and 87.1% for EUS/ERCP combination. EUS-FNA showed higher overall performances compared with ERCP (P < 0.001), whereas EUS/ERCP combination was superior to EUS-FNA alone (P-value < 0.001). EUS-FNA showed higher sensitivity and accuracy compared with ERCP for pancreatic masses (n = 187, both P-values < 0.001) but not for biliary lesions (n = 76, both P-values = 0.847). Sensitivity and accuracy of EUS/ERCP combination were superior to those of EUS-FNA for both pancreatic and biliary lesions (both P-values < 0.001). For patients with large mass (≥ 4 cm), there was no significant differences between ERCP/EUS combination and EUS-FNA (P-value = 0.31).
CONCLUSIONS Same-session EUS-FNA and ERCP combination was superior to EUS-FNA for both pancreatic masses and biliary lesions. Same-session EUS/ERCP combination can be considered a proper diagnostic method for suspected malignant biliary obstruction regardless of the origin of lesions. On the other hand, EUS-FNA alone was sufficient for diagnosis compared with EUS/ERCP combination in cases with large mass. Strategic diagnostic approach, according to clinical features of individual patient, is required.
PubMed IF 3.5 소화기내과
27752019

제1저자 이태민 · 교신저자 김학령

, , , , , ,
Association between epicardial adipose tissue thickness and parameters of target organ damage in patients undergoing coronary angiography.
Hypertens Res. 2019;42(4):549-557.

Abstract
Epicardial adipose tissue (EAT), metabolically active visceral fat, is easily measurable using transthoracic echocardiography (TTE). This study aimed to clarify the relationship between EAT thickness and parameters for target organ damage (TOD). A total of 338 consecutive patients (64.5 ± 10.9 years, 58.0% men) undergoing invasive coronary angiography in a stable condition were prospectively enrolled. TTE was performed, and the EAT thickness was measured perpendicular to the right ventricular free wall at end-systole. We investigated TOD parameters, including the estimated glomerular filtration rate, proteinuria, left ventricular (LV) mass index (LVMI), septal e' velocity, E/e', brachial-ankle pulse wave velocity, ankle-brachial index, aortic pulse pressure (APP), and presence of coronary artery disease (CAD). APP and CAD were assessed by invasive cardiac catheterization. Most patients (77.5%) had significant CAD (≥50% stenosis). In Pearson's bivariate correlation analyses, the EAT thickness was significantly correlated with the septal e' velocity (r = -0.203, P < 0.001) and E/e' (r = 0.217, P < 0.001), but not with other TOD parameters (P > 0.05). Multiple linear regression analysis showed that the correlations of the EAT thickness with septal e' velocity (β = -0.172, P = 0.047) and E/e' (β = 0.207, P = 0.011) remained significant even after adjusting for potential confounders. EAT thickness is more closely related to LV diastolic function than other TOD parameters, including renal function, LVMI, arterial stiffness, peripheral artery disease, and CAD. These findings provide additional evidence for the potential role of EAT in the pathogenesis of LV diastolic dysfunction.
PubMed IF 5 순환기내과
27742019

제1저자 장성아, 김형관 · 교신저자 김덕경

, , ,
Acute Hemodynamic Changes after Single Administration of Udenafil in Pulmonary Arterial Hypertension: a Phase IIa Study.
Korean Circ J. 2019;49(4):353-360.

Abstract
BACKGROUND AND OBJECTIVES Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose.
METHODS Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration.
RESULTS The mPAP significantly decreased in both the U50 and U100 (-11 mmHg and -8 mmHg from baseline, respectively, p<0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=-8.5 mmHg and Δ=-14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events.
CONCLUSIONS This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01553721.
PubMed IF 3.4 순환기내과
27732019

제1저자 하혜림 · 교신저자 오도연

, , , , , ,
Dynamics of Soluble Programmed Death-Ligand 1 (sPDL1) during Chemotherapy and Its Prognostic Implications in Cancer Patients: Biomarker Development in Immuno-oncology.
Cancer Res Treat. 2019;51(2):832-840.

Abstract
PURPOSE The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients.
MATERIALS AND METHODS From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed.
RESULTS The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003).
CONCLUSION The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.
PubMed IF 4.2 혈액종양내과
27722019

제1저자 이미소 · 교신저자 임석아

, , , , , , , , , , , , , , ,
Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.
Cancer Res Treat. 2019;51(2):451-463.

Abstract
PURPOSE Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.
MATERIALS AND METHODS The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
RESULTS AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
CONCLUSION Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
PubMed IF 4.2 혈액종양내과
27712019

제1저자 배지윤 · 교신저자 박완범

, , , , , , , , , , ,
Efficacy of Intranasal Administration of the Recombinant Endolysin SAL200 in a Lethal Murine Staphylococcus aureus Pneumonia Model.
Antimicrob Agents Chemother. 2019;63(4):AAC.02009-18.

Abstract
SAL200 is derived from a phage endolysin and is a novel candidate drug for the treatment of Staphylococcus aureus infection. We investigated the efficacy of the recombinant endolysin SAL200 in a lethal murine pneumonia model. Lethal pneumonia was established by intranasally administering a methicillin-susceptible (Newman) or methicillin-resistant (LAC) S. aureus strain into BALB/c mice. The mice were treated with a single intranasal administration of SAL200 or phosphate-buffered saline at 2 h after S. aureus infection. The survival rates were recorded until 60 h after the bacterial challenge. The bacterial loads in the lungs and blood, histopathology of lung tissues, and serum cytokine levels were evaluated following the S. aureus challenge. The SAL200-treated group and control group exhibited 90% to 95% and 10% to 40% survival rates, respectively. The bacterial loads in the lungs of the SAL200-treated group were significantly lower by ∼10-fold than those of the control group as early as 1 h after treatment. Histopathologic recovery of pneumonia was observed in the SAL200-treated mice. The cytokine levels were comparable between groups. These results suggest that direct administration of SAL200 into the lungs could be a potential adjunct treatment against severe pneumonia caused by S. aureus.
PubMed IF 4.2 감염내과
27702019

제1저자 심지수 · 교신저자 강혜련

, , , , , , , ,
The Presence of HLA-B75, DR13 Homozygosity, or DR14 Additionally Increases the Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in HLA-B*58:01 Carriers.
J Allergy Clin Immunol Pract. 2019;7(4):1261-1270.

Abstract
BACKGROUND Although HLA-B*58:01 is a well-known risk factor for the development of allopurinol-induced severe cutaneous adverse reactions (SCARs), most of the HLA-B*58:01 carriers do not suffer from SCARs despite a long-term use of allopurinol. This suggests that there are other risk factors that determine the fate of HLA-B*58:01 carriers.
OBJECTIVE The aim of this study was to investigate the additional genetic factors that increase the risk of allopurinol-induced SCARs in HLA-B*58:01 carriers.
METHODS The incidence of allopurinol-induced SCARs was investigated according to coexisting HLA alleles in all subjects with HLA-B*58:01 who took allopurinol between 2003 and 2017. The allopurinol tolerant group was defined as a group who took allopurinol for more than 60 days without developing hypersensitivity and was compared with the allopurinol-induced SCAR group.
RESULTS Among the retrospective cohort consisting of 367 HLA-B*58:01 carriers treated with allopurinol, 11 (3.0%) were diagnosed with allopurinol-induced SCARs. When HLA-B75, DR13 homozygosity, or DR14 was present, the incidence of SCARs increased up to 22.2% (odds ratio [OR], 19.568; P = .015), 20.0% (OR, 38.458; P = .001), and 10.7% (OR, 19.355; P = .004), respectively. Among the 153 HLA-B*58:01 carriers with chronic renal insufficiency (CRI), the incidence of SCARs doubled to 6.5% and further increased to 40%, 30%, and 37.5% in the presence of HLA-B75, DR13 homozygosity, or DR14, respectively.
CONCLUSIONS Secondary screening with HLA-B75, DR13 homozygosity, and DR14 in addition to primary screening with HLA-B*58:01 would enable a more accurate prediction of SCAR occurrence, especially in patients with CRI.
PubMed IF 6.6 알레르기내과
27692019

제1저자 박흥우 · 교신저자 박흥우

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Efficacy of the HLA-B∗58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.
J Allergy Clin Immunol Pract. 2019;7(4):1271-1276.

Abstract
BACKGROUND Thus far, human leukocyte antigen (HLA)-B^∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs).
OBJECTIVE To determine the usefulness of prospective screening for the HLA-B^∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment.
METHODS We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B^∗58:01 allele. Of these, 503 HLA-B^∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B^∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively.
RESULTS Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029).
CONCLUSIONS The present study demonstrated the clinical usefulness of the HLA-B^∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.
PubMed IF 6.6 알레르기내과
27682019

제1저자 김윤준,박중원 · 교신저자 박중원

, , , , , , , , , , , , ,
Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial.
J Hepatol. 2019;70(4):684-691.

Abstract
BACKGROUND & AIMS Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC.
METHODS In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS).
RESULTS For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006).
CONCLUSION Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC.
LAY SUMMARY For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.
PubMed IF 40.1 소화기내과
27672019

제1저자 이진재, 김세훈 · 교신저자 장윤석, 김봉수

, , , , , , , , ,
Different upper airway microbiome and their functional genes associated with asthma in young adults and elderly individuals.
Allergy. 2019;74(4):709-719.

Abstract
BACKGROUND Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.
METHODS Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non-asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high-throughput sequencing.
RESULTS The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non-asthmatics in each age group. Different bacteria were related to FEV_1% predicted in each age group. Genes related to lysine degradation, N-glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non-asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis-which may all be related to increased inflammation and colonization of pathogenic bacteria-were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.
CONCLUSIONS These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
PubMed IF 11.3 알레르기내과
27662019

제1저자 오주은 · 교신저자 박경수

, , , , , , , , , , , ,
Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components.
Sci Rep. 2019;9(1):5343.

Abstract
Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.
PubMed IF 4.9 순환기내과
27652019

제1저자 최수연 · 교신저자 최수연, 최승호

, , , , , , ,
Genome-wide association study of coronary artery calcification in asymptomatic Korean populations.
PLoS One. 2019;14(3):e0214370.

Abstract
Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state.
PubMed IF 2.8 순환기내과
27642019

제1저자 조재영 · 교신저자 이창훈

, , , , , , , , , , ,
Risk of acute exacerbations in chronic obstructive pulmonary disease associated with biomass smoke compared with tobacco smoke.
BMC Pulm Med. 2019;19(1):68.

Abstract
BACKGROUND Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke.
METHODS To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β^') of tobacco smoke exposure ≥10 pack-years (β = - 0.13 and β^' = - 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations.
RESULTS Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56-1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed.
CONCLUSIONS Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.
PubMed IF 3.1 호흡기내과
27632019

제1저자 차재황 · 교신저자 이현정

, , , , , , , , , , ,
Long-term outcomes according to additional treatments after endoscopic resection for rectal small neuroendocrine tumors.
Sci Rep. 2019;9(1):4911.

Abstract
The present study aimed to investigate treatment strategies determining additional treatment after endoscopic resection (ER) of rectal neuroendocrine tumor (NET)s and long-term outcomes of endoscopically resected rectal NETs. We analyzed a total of 322 patients medical records of patients who underwent ER for rectal NETs. Rectal NETs initially resected as polyps and treated with conventional endoscopic mucosal resection (EMR) were observed more frequently in the non-curative group (P = 0.041 and P = 0.012, respectively). After ER, only 44 of the 142 patients (31.0%) who did not meet the criteria for curative resection received additional salvage treatment. In multivariate analysis, lesions diagnosed via biopsies (OR, 0.096; P = 0.002) or suspected as NETs initially (OR, 0.04; P = 0.001) were less likely to undergo additional treatment. Positive lymphovascular invasion (OR 61.971; P < 0.001), positive (OR 75.993; P < 0.001), or indeterminate (OR 13.203; P = 0.001) resection margins were more likely to undergo additional treatment. Although lymph node metastasis was found in 6 patients, none experienced local or metastatic tumor recurrence during the median follow-up of 40.49 months. Long-term outcomes after ER for rectal NETs were excellent. The prognosis showed favorable outcomes regardless of whether patients receive additional salvage treatments.
PubMed IF 4.9 소화기내과
27622019

제1저자 서원우, 서정원 · 교신저자 최동주

, , , , , , ,
Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion-Gauging Infarct Size in Patients with Acute ST-segment Elevation Myocardial Infarction (ICEBERG).
Int Heart J. 2019;60(2):255-263.

Abstract
Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 μg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm³, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.
PubMed IF 1.4 순환기내과
27612019

제1저자 박찬순 박진주 · 교신저자 최동주

, , , , , , , , , , , , , , , ,
Characteristics, Outcomes, and Treatment of Heart Failure With Improved Ejection Fraction.
J Am Heart Assoc. 2019;8(6):e011077.

Abstract
Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and β-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. β-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose β-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of β-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.
PubMed IF 6 순환기내과
27602019

제1저자 최원석 · 교신저자 최의근

, , , ,
Anatomic Conformation of Renal Sympathetic Nerve Fibers in Living Human Tissues.
Sci Rep. 2019;9(1):4831.

Abstract
Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 μm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.
PubMed IF 4.9 순환기내과
27592019

제1저자 임병관 박진주 · 교신저자 최동주

, , , , , ,
Fimasartan for Remodeling after Myocardial Infarction.
J Clin Med. 2019;8(3):jcm8030366.

Abstract
An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague⁻Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.
PubMed IF 3.3 순환기내과

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