SCI 발표논문
2016년 247편
- 1872016
제1저자 이하정, 이재욱 · 교신저자 양승희
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Cln 3-requiring 9 is a negative regulator of Th17 pathway-driven inflammation in anti-glomerular basement membrane glomerulonephritis.Am J Physiol Renal Physiol. 2016;311(3):F505-19.
PubMed IF 3.6 신장내과Abstract
T helper 17 (Th17) lymphocytes promote renal inflammation in anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), and signal transducer and activator of transcription 3 (STAT3) mediates activation of Th17 lymphocytes by IL-6 and transforming growth factor-β (TGF-β). Cln 3-requiring 9 (Ctr9), a subunit of RNA polymerase-associated factor complex (PAFc), regulates the transcription of IL-6/STAT3-dependent genes. Here, we investigated the role of Ctr9 in regulating Th17-driven inflammation in anti-GBM GN. In mice, STAT3β or IL-17 knockout ameliorated anti-GBM autoantibody-induced renal injury. This phenomenon was associated with decreases in retinoic acid receptor-related orphan receptor γt (RORγt), IL-17, phosphorylated STAT3, and proinflammatory cytokines. Compared with wild-type mice, Ctr9 increased in both STAT3β(-/-) and IL-17(-/-) mice injected with anti-GBM IgG, showing a negative correlation with Th17-related transcripts. Small interfering RNA (siRNA)-mediated knockdown of Ctr9 in intrarenal lymphocytes further upregulated Th17-related transcripts, consistent with repression of Th17 differentiation by Ctr9. Interestingly, Ctr9 was also expressed in human and mouse mesangial cells and downregulated in response to anti-GBM IgG or to TGF-β plus IL-17. Ctr9 in mesangial cells was even more repressed in the presence of both anti-GBM IgG and Th17-activating cytokines. Consistent with these findings, renal biopsies obtained from patients with anti-GBM GN showed consistent downregulation of Ctr9 and upregulation of phosphorylated STAT3 and IL-17 in the glomerulus. We conclude that Ctr9 is a negative regulator of Th17 differentiation in anti-GBM GN and repressed by anti-GBM IgG and IL-17 in mesangial cells.
- 1862016
제1저자 장미경 · 교신저자 김상완
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Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.J Bone Miner Metab. 2016;34(5):532-9.
PubMed IF 2.9 내분비대사내과Abstract
Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 μg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.
- 1852016
제1저자 조유리 · 교신저자 윤정환
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Hypoxia Enhances Tumor-Stroma Crosstalk that Drives the Progression of Hepatocellular Carcinoma.Dig Dis Sci. 2016;61(9):2568-77.
PubMed IF 2.8 소화기내과Abstract
BACKGROUND Crosstalk between tumor cells and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). Hypoxia, a common feature of advanced HCC, has been shown to modulate the evolution of the tumor microenvironment. In this study, we investigated the effect of hypoxia on tumor-stroma crosstalk in HCC.
METHODS Human HCC cell lines (Huh-BAT, SNU-475) were cocultured with an activated human hepatic stellate cell line (HSCs; LX-2) under either normoxic or hypoxic conditions. Cell growth was evaluated with the MTS assay. Apoptotic signaling cascades were assessed by immunoblot analysis. Expression of CD31 and phosphorylated (p-) Akt in HCC tissues was detected by immunohistochemistry.
RESULTS Coculturing HCC cells with HSCs under hypoxic conditions enhanced their proliferation, migration, and resistance to bile acid (BA)-induced apoptosis compared to coculturing under normoxic conditions. Under hypoxia, of various HSC-derived growth factors, PDGF-BB was the most up-regulated, leading to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in HCC cells. Immunohistochemical study also revealed that p-Akt was highly expressed in hypoxic, hypovascular HCC as compared to hypervascular HCC. Neutralizing antisera to PDGF-BB or a PI3K inhibitor attenuated the proliferation of HCC cells cocultured with HSCs, and sensitized HCC cells to BA-induced apoptosis, especially under hypoxic conditions.
CONCLUSIONS In conclusion, hypoxic HSC-derived PDGF-BB stimulates the proliferation of HCC cells through activation of the PI3K/Akt pathway, while the inhibition of PDGF-BB or PI3K/Akt pathways enhances apoptotic cell death. Targeting tumor-stroma crosstalk might be a novel therapy in the management of human HCCs.
- 1842016
제1저자 이주명 · 교신저자 구본권, 천기정
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Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron Emission Tomography.Circ Cardiovasc Imaging. 2016;9(9):CIRCIMAGING.116.004768.
PubMed IF 9.1 순환기내과Abstract
BACKGROUND Recent evidence suggests that the diagnostic accuracy of myocardial perfusion imaging is improved by quantifying stress myocardial blood flow (MBF) in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia positron emission tomography ((13)NH3-PET) diagnostic panel, including stress MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction with relative perfusion defect (PD) assessments to better detect functionally significant coronary artery stenosis.
METHODS AND RESULTS A total of 130 patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET and invasive coronary angiography with fractional flow reserve (FFR) measurement. Diagnostic accuracy, optimal cut points, and discrimination indices of respective (13)NH3-PET quantitative measures were compared, with FFR as standard reference. The capacity to discern disease with stepwise addition of stress MBF, CFR, and RFR to qualitatively assessed relative PD was also gauged, using the category-free net reclassification index. All quantitative measures showed significant correlation with FFR (PET-derived CFR, r=0.388; stress MBF, r=0.496; and RFR, r=0.780; all P<0.001). Optimal respective cut points for FFR ≤0.8 and ≤0.75 were 1.99 and 1.84 mL/min per g for stress MBF and 2.12 and 2.00 for PET-derived CFR. Discrimination indices of quantitative measures that correlated with FFR ≤0.8 were all significantly higher than that of relative PD (area under the curve: 0.626, 0.730, 0.806, and 0.897 for relative PD, CFR, stress MBF, and RFR, respectively; overall comparison P<0.001). The capacity for functionally significant coronary stenosis was incrementally improved by the successive addition of CFR (net reclassification index=0.629), stress MBF (net reclassification index=0.950), and RFR (net reclassification index=1.253; all P<0.001) to relative PD.
CONCLUSIONS Integrating quantitative (13)NH3-PET measures with qualitative myocardial perfusion assessment provides superior diagnostic accuracy and improves the capacity to detect functionally significant coronary artery stenosis.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01621438 and NCT01366404.
- 1832016
제1저자 서기현, 김민재 · 교신저자 송경호
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Cancer-specific incidence rates of tuberculosis: A 5-year nationwide population-based study in a country with an intermediate tuberculosis burden.Medicine (Baltimore). 2016;95(38):e4919.
PubMed IF 2 감염내과Abstract
Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis.We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20-99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population.A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17-2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57-3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36-1.51).The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies.
- 1822016
제1저자 김윤기 · 교신저자 서정원
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Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.JACC Cardiovasc Interv. 2016;9(16):1680-90.
PubMed IF 12.7 순환기내과Abstract
OBJECTIVES The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU).
BACKGROUND PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity.
METHODS Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU.
RESULTS A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813).
CONCLUSIONS The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.
- 1812016
제1저자 김문석 · 교신저자 송경호
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Electronic Alerts with Automated Consultations Promote Appropriate Antimicrobial Prescriptions.PLoS One. 2016;11(8):e0160551.
PubMed IF 2.8 감염내과Abstract
BACKGROUND To promote appropriate antimicrobial use in bloodstream infections (BSIs), we initiated an intervention program consisting of electronic alerts and automated infectious diseases consultations in which the identification and antimicrobial susceptibility test (ID/AST) results were reported.
METHODS We compared the appropriateness of antimicrobial prescriptions and clinical outcomes in BSIs before and after initiation of the program. Appropriateness was assessed in terms of effective therapy, optimal therapy, de-escalation therapy, and intravenous to oral switch therapy.
RESULTS There were 648 BSI episodes in the pre-program period and 678 in the program period. The proportion of effective, optimal, and de-escalation therapies assessed 24 hours after the reporting of the ID/AST results increased from 87.8% (95% confidence interval [CI] 85.5-90.5), 64.4% (95% CI 60.8-68.1), and 10.0% (95% CI 7.5-12.6) in the pre-program period, respectively, to 94.4% (95% CI 92.7-96.1), 81.4% (95% CI 78.4-84.3), and 18.6% (95% CI 15.3-21.9) in the program period, respectively. Kaplan-Meier analyses and log-rank tests revealed that the time to effective (p<0.001), optimal (p<0.001), and de-escalation (p = 0.017) therapies were significantly different in the two periods. Segmented linear regression analysis showed the increase in the proportion of effective (p = 0.015), optimal (p<0.001), and de-escalation (p = 0.010) therapies at 24 hours after reporting, immediately after program initiation. No significant baseline trends or changes in trends were identified. There were no significant differences in time to intravenous to oral switch therapy, length of stay, and 30-day mortality rate.
CONCLUSION This novel form of stewardship program based on intervention by infectious disease specialists and information technology improved antimicrobial prescriptions in BSIs.
- 1802016
제1저자 박진선, 신준한 · 교신저자 김효수
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Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).Drug Des Devel Ther. 2016;10:2599-609.
PubMed IF 6.1 순환기내과Abstract
The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden.
- 1792016
제1저자 박재윤 · 교신저자 이정표
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Early initiation of continuous renal replacement therapy improves survival of elderly patients with acute kidney injury: a multicenter prospective cohort study.Crit Care. 2016;20(1):260.
PubMed IF 11.4 신장내과Abstract
BACKGROUND Continuous renal replacement therapy (CRRT) is essential in the management of critically ill patients with acute kidney injury (AKI). However, the optimal timing for initiating CRRT remains controversial, especially in elderly patients. Therefore, we investigated the outcomes of early CRRT initiation in elderly patients with AKI.
METHODS A total of 607 patients ≥65 years of age who started CRRT due to AKI between August 2009 and December 2013 were prospectively enrolled. They were divided into two groups based on the median 6-hour urine output immediately before CRRT initiation. Propensity score matching was used to compare the overall survival rate, CRRT duration, and hospitalization duration.
RESULTS The median age of both groups was 73.0 years, and 60 % of the patients were male. The most common cause of AKI was sepsis. In the early CRRT group, the mean arterial pressure was higher, but the prothrombin time and total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were lower. The overall cumulative survival rate was higher in the early CRRT group (log-rank P < 0.01). Late CRRT initiation was associated with a higher mortality rate than early initiation after adjusting for age, sex, the Charlson comorbidity index, systolic arterial pressure, prothrombin time, the total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels, cumulative fluid balance and diuretic use (hazard ratio, 1.35; 95 % confidence interval 1.06, 1.71, P = 0.02). Following propensity score matching, patient survival was significantly better in the early CRRT group than in the late CRRT group (P < 0.01). The total duration of hospitalization from the start of CRRT was shorter among the survivors when CRRT was started earlier (26.7 versus 39.1 days, P = 0.04).
CONCLUSION A better prognosis can be expected if CRRT is applied early in the course of AKI in critically ill, elderly patients.
- 1782016
제1저자 안정남, 안성복 · 교신저자 김영훈, 임춘수
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Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea.PLoS One. 2016;11(8):e0160607.
PubMed IF 2.8 신장내과Abstract
BACKGROUND Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported.
METHODS AND FINDINGS We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66-3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22-2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors.
CONCLUSIONS In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients.
- 1772016
제1저자 조유리, 이윤빈 · 교신저자 이정훈, 윤정환
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Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14.PLoS One. 2016;11(8):e0160822.
PubMed IF 2.8 소화기내과Abstract
Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of AS1411-aptamers in SNU-761 HCC cells. We investigated the in vivo effects of the AS1411-aptamer using BALB/c nude mice in a subcutaneous xenograft model with SNU-761 cells. Treatment with a modified AS1411-aptamer significantly decreased in vitro (under normoxic [P = 0.035] and hypoxic [P = 0.018] conditions) and in vivo (under normoxic conditions, P = 0.041) HCC cell proliferation compared to control aptamers. AS1411- and control aptamers failed to control HCC cell proliferation. However, AS1411- and the modified AS1411-aptamer did not induce caspase activation. Decrease in cell growth by AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In a microarray, AS1411 significantly enhanced galectin-14 expression. Suppression of HCC cell proliferation by the modified AS1411-aptamer was attenuated by galectin-14 siRNA transfection. Modified AS1411-aptamer suppressed HCC cell growth in vitro and in vivo by up-regulating galectin-14 expressions. Modified AS1411-aptamers may have therapeutic potential as a novel targeted therapy for HCC.
- 1762016
제1저자 유승근, 이승복, 김수진 · 교신저자 박영주, 이규언, 서정선
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Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers.PLoS Genet. 2016;12(8):e1006239.
PubMed IF 3.9 내분비대사내과Abstract
Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8-PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non-BRAF-Non-RAS (NBNR), as well as BRAF-like and RAS-like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8-PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.
- 1752016
제1저자 이희선 · 교신저자 윤연이
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The Incremental Prognostic Value of Cardiac Computed Tomography in Comparison with Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.PLoS One. 2016;11(8):e0160188.
PubMed IF 2.8 순환기내과Abstract
BACKGROUND Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT.
MATERIALS AND METHODS A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies).
RESULTS During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001).
CONCLUSION Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS.
- 1742016
제1저자 허진 · 교신저자 김효수
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KAI1(CD82)-DARC(CD234) axis in the stem cell niche.Cell Cycle. 2016;15(15):1945-7.
- 1732016
제1저자 박효은, 곽민선 · 교신저자 최수연, 김동희
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Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study.J Clin Endocrinol Metab. 2016;101(8):3134-43.
PubMed IF 5.4 소화기내과Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown.
OBJECTIVE This study investigated the longitudinal association between NAFLD and CAC score.
DESIGN AND SETTING This study is a longitudinal cohort study performed in a healthcare center.
PARTICIPANTS Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography.
MAIN OUTCOME MEASURES CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed.
RESULTS More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043).
CONCLUSIONS NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.
- 1722016
제1저자 최수연 · 교신저자 성지동
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Combined effects of exercise capacity and coronary atherosclerotic burden on all-cause mortality in asymptomatic Koreans.Atherosclerosis. 2016;251:396-403.
PubMed IF 7.1 순환기내과Abstract
BACKGROUND AND AIMS Both exercise capacity and coronary artery calcium score (CACS) are important prognostic factors in cardiovascular outcome. Yet, whether there is a significant interaction between these two factors in influencing clinical outcome is still uncertain. This study investigated the combined effects of exercise capacity and CACS on all-cause mortality in an asymptomatic population.
METHODS From multicenter registry of health screening, a retrospective cohort of 25,972 asymptomatic subjects, who underwent both CACS and treadmill exercise test, was included in the final dataset for analysis. Outcome was defined as all-cause mortality, which was obtained from national mortality registry.
RESULTS The mean age of study subjects was 53.7 ± 7.7 years and 81.5% of them were males. Median follow-up duration was 5.5 (IQR 3.6-7.5) years and 226 (0.9%) cases of all-cause mortality occurred. In multivariate Cox's proportional hazard model with interaction term, exercise capacity ≥10 METs (HR 0.684, 95% CI 0.483-0.971) and CACS ≥400 (HR 3.328, 95% CI 1.850-5.988) were significant predictors of all-cause mortality. In patients with higher exercise capacity, the effect of high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. The HR for all-cause mortality of CACS ≥400, in those with lower exercise capacity, is estimated to be about three times of that in those with higher exercise capacity (HR 3.328 in <10 METs vs. 1.108 in ≥10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, creatinine, alanine transaminase and albumin.
CONCLUSIONS The effect of high CACS on all-cause mortality is lessened by good exercise capacity in the asymptomatic population. Good physical fitness may reduce the adverse effect of high coronary atherosclerotic burden.
- 1712016
제1저자 강지훈,허진,강진아 · 교신저자 김효수
, , , , , , , , ,
Priming mobilized peripheral blood mononuclear cells with the "activated platelet supernatant" enhances the efficacy of cell therapy for myocardial infarction of rats.Cardiovasc Ther. 2016;34(4):245-53.
PubMed IF 2.8 순환기내과Abstract
AIM Various methods are used to augment the efficacy of cell therapy in myocardial infarction (MI). In this study, we used the "activated platelet supernatant (APS)" to prime autologous "granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells ((mob) PBMCs)" and investigated the efficacy of cell-based therapy in MI.
METHOD Rat (mob) PBMCs were isolated after daily subcutaneous injections of G-CSF at 100 μg/kg for 3 days. APS was isolated separately after activating rat platelets with thrombin 0.5 U/mL for 2 hours. Priming was performed with APS for 6 hours. To check the paracrine effect of primed (mob) PBMCs, we used the 36-hour culture supernatant of the primed cells. A rat MI model was used for an in vivo model.
RESULT Cytokines such as IL-1β, IL-10, and TGFβ were 3.7±0.9-fold, 3.4±1.2-fold, and 1.2±0.1-fold higher in APS, respectively, compared with naïve platelet supernatant. By APS priming, (mob) PBMCs showed M2 polarization and upregulation of angiogenic molecules (i.e., TEK, IL-10, CXCL1, and CX3CR1). APS-primed (mob) PBMCs had a 2.3-fold increased adhesion ability, induced by upregulated integrins. Rat endothelial cells cultured in the 36-hour culture supernatant of APS-primed (mob) PBMCs showed a 1.6-fold augmented proliferation and capillary network formation. In vivo transplantation of APS-primed (mob) PBMCs into rat MI models showed a significant trend of reduction in fibrosis area (P=.001) and wall thinning (P=.030), which lead to improvement in cardiac function measured by echocardiography.
CONCLUSION Our data reveal that APS priming can enhance the wound-healing potential of (mob) PBMCs. APS priming may be a promising method for cell-based therapy of MI.
- 1702016
제1저자 박진균 · 교신저자 이은봉
, , , , , , , , ,
Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial.Clin Ther. 2016;38(8):1858-1868.e2.
PubMed IF 3.7 류마티스내과Abstract
PURPOSE The aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA).
METHODS A randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization.
FINDINGS The allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (-9.0 [-23.8 to -0.4] vs -2.2 [-16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI-defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles.
IMPLICATIONS GCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116.
- 1692016
제1저자 박종선 · 교신저자 이상민
, , , , , ,
Anti-inflammatory Effect of Erdosteine in Lipopolysaccharide-Stimulated RAW 264.7 Cells.Inflammation. 2016;39(4):1573-81.
PubMed IF 5.4 호흡기내과Abstract
Erdosteine is widely used as a mucolytic agent and also has free radical scavenging and antioxidant activities. However, little is known about the mechanisms of the anti-inflammatory effect of erdosteine. We investigated the effect of erdosteine on the activation of the nuclear factor (NF)-kB/inhibitor of NFkB (IkB), and the mitogen-activated protein kinase (MAPK) and Akt pathways in the mouse macrophage cell line RAW 264.7. Cultured RAW 264.7 cells were pretreated with erdosteine and stimulated with lipopolysaccharide (LPS). In Western blotting, pretreatment with erdosteine inhibited the IkBα degradation induced in RAW 264.7 cells by LPS. LPS-induced IkB kinase (IKK) activity and NF-kB transcription were inhibited by pretreatment with erdosteine. Production of IL-6 and IL-1β was also inhibited by erdosteine pretreatment. However, erdosteine did not inhibit LPS-induced phosphorylation of Akt and MAPKs. These results suggest that the anti-inflammatory effect of erdosteine in mouse macrophages is mediated through inhibition of LPS-induced NF-kB activation.
- 1682016
제1저자 장동기 · 교신저자 류지곤
, , , , , ,
Risk Factors for Progression or Malignancy in Main-Duct and Mixed-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas.Pancreas. 2016;45(7):1027-31.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy.
METHODS Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion.
RESULTS Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy.
CONCLUSIONS A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.
- 1672016
제1저자 박재윤 · 교신저자 이정표
, , , , , , , , , , , , , , ,
Superior outcomes of kidney transplantation compared with dialysis: An optimal matched analysis of a national population-based cohort study between 2005 and 2008 in Korea.Medicine (Baltimore). 2016;95(33):e4352.
PubMed IF 2 신장내과Abstract
Data regarding kidney transplantation (KT) and dialysis outcomes are rare in Asian populations. In the present study, we evaluated the clinical outcomes associated with KT using claims data from the Korean national public health insurance program. Among the 35,418 adult patients with incident dialysis treated between 2005 and 2008 in Korea, 1539 underwent KT. An optimal balanced risk set matching was attempted to compare the transplant group with the control group in terms of the overall survival and major adverse cardiac event-free survival. Before matching, the dialysis group was older and had more comorbidities. After matching, there were no differences in age, sex, dialysis modalities, or comorbidities. Patient survival was significantly better in the transplant group than in the matched control group (P < 0.001). In addition, the transplant group showed better major adverse cardiac event-free survival than the dialysis group (P < 0.001; hazard ratio, 0.49; 95% confidence interval, 0.32-0.75). Korean patients with incident dialysis who underwent long-term dialysis had significantly more cardiovascular events and higher all-cause mortality rates than those who underwent KT. Thus, KT should be more actively recommended in Korean populations.
- 1662016
제1저자 유수종 · 교신저자 윤정환
, , , , , , , , , , , , ,
Percutaneous ethanol injection therapy is comparable to radiofrequency ablation in hepatocellular carcinoma smaller than 1.5 cm: A matched case-control comparative analysis.Medicine (Baltimore). 2016;95(35):e4551.
PubMed IF 2 소화기내과Abstract
Although percutaneous ethanol injection therapy (PEIT) is best indicated for patients with small hepatocellular carcinoma (HCC), the survival advantage of PEIT needs confirmation in real-world practice. This study was approved by the institutional review board, and the informed consent was waived. The study included 535 consecutive patients with newly diagnosed early stage (Barcelona Clinic Liver Cancer [BCLC] 0 or A) HCC who underwent initially radiofrequency ablation (RFA) (n = 288) or PEIT (n = 247) from January 2005 to December 2010. The primary outcome was overall survival (OS) and the secondary outcome was time to progression (TTP). The longest diameters of tumors of the groups differed significantly and larger for RFA group than PEIT group (P < 0.001; 1.94 ± 0.65 cm vs 1.60 ± 0.50 cm, respectively). The 5-year OS rates were 72.2% in the RFA group and 67.4% in the PEIT group (P = 0.608). Even after propensity score matching, OS rates between the 2 groups were similar (5-year OS: 72.8% with RFA [n = 175] and 68.0% with PEIT [n = 175]) (P = 0.709). Moreover, in patients with the longest diameter of tumors (≤1.5 cm), multivariate Cox regression analysis showed that the treatment modality was not a significant prognosticator for OS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 0.828-3.449; P = 0.149) and time to progression (HR, 1.160; 95% CI, 0.773-1.740; P = 0.474). PEIT and RFA show equal effectiveness in treating HCCs <1.5 cm in terms of OS and time to progression.
- 1652016
제1저자 한정규 · 교신저자 김효수
, , , , , , , , , , , , , , ,
Interaction between platelets and endothelial progenitor cells via LPA-Edg-2 axis is augmented by PPAR-δ activation.J Mol Cell Cardiol. 2016;97:266-77.
PubMed IF 4.9 순환기내과Abstract
BACKGROUND Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor regulating cell metabolism. The role of PPAR-δ in late endothelial progenitor cells (EPCs) has not been fully elucidated. We aim to understand the effects of PPAR-δ activation on late EPC and to reveal the underlying mechanism.
METHODS AND RESULTS Treatment with a highly selective PPAR-δ agonist (GW501516) induced proliferation of late EPCs and enhanced their vasculogenic potential. Search for the target molecule of PPAR-δ activation revealed endothelial differentiation gene (Edg)-2. Chromatin immunoprecipitation and promoter assays demonstrated that Edg-2 gene was specifically induced by PPAR-δ through direct transcriptional activation. Lysophosphatidic acid (LPA), an Edg ligand, mimicked the pro-vasculogenic effects of GW501516 in late EPCs whereas Edg antagonist (Ki16425) blocked these effects. Edg-2 is a membrane receptor for LPA which is a major growth factor from activated platelets. Thus, the interaction between platelets and late EPCs via the LPA-Edg-2 axis was assessed. Platelet supernatant boosted the pro-vasculogenic effects of GW501516, which was reversed by antagonist to PPAR-δ (GSK0660) or Edg (Ki16425). Both of in vivo Matrigel plug model and mouse skin punch-wound model demonstrated that the combination of platelets and PPAR-δ-activated late EPCs synergistically enhanced vascular regeneration.
CONCLUSIONS There exists a synergistic interaction between human platelets and late EPCs leading to vascular regeneration. This interaction consists of LPA from platelets and its receptor Edg-2 on the surface of EPCs and can be potentiated by PPAR-δ activation in EPCs. A PPAR-δ agonist is a good candidate to achieve vasculogenesis for ischemic vascular disease.
- 1642016
제1저자 이주엽 · 교신저자 김나영
, , , , , , , , , , , , , , ,
Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth quadruple therapy for the first-line eradication of Helicobacter pylori: a prospective, multi-center, randomized clinical trial.BMC Gastroenterol. 2016;16(1):79.
PubMed IF 3.2 소화기내과Abstract
BACKGROUND The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy.
METHODS In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication.
RESULTS Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040).
CONCLUSIONS Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy.
TRIAL REGISTRATION ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
- 1632016
제1저자 양예원 · 교신저자 임석아, 김태용
, , , , , , , , , , , , ,
Prognostic impact of AJCC response criteria for neoadjuvant chemotherapy in stage II/III breast cancer patients: breast cancer subtype analyses.BMC Cancer. 2016;16:515.
PubMed IF 4.1 혈액종양내과Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is a standard treatment for stage II/III breast cancer patients, and response to NAC is a useful prognostic marker. Since its introduction, 6-8 cycles of NAC has become the standard regimen to improve the outcome of these patients. The purpose of this study is to evaluate the prognostic impact of the American Joint Committee on Cancer (AJCC) response criteria and this tool's usefulness in four different breast cancer subtypes.
METHODS We conducted a retrospective cohort study of clinical stage II/III breast cancer patients who received NAC of more than 6 cycles. Response after NAC and the clinicopathological factors were reviewed. AJCC response criteria for NAC were adopted from the AJCC Manual, 7th edition: complete response (CR), partial response (PR), and no response (NR).
RESULTS A total of 183 patients were enrolled; 22 (12.0 %), 123 (67.2 %), and 38 (20.8 %) patients showed CR, PR, and NR, respectively. The AJCC response was significantly associated with relapse-free survival (RFS) (P < 0.001), whereas pathologic CR (pCR), the current gold standard for response evaluation for NAC, was not (P = 0.140). AJCC response was a significant prognostic factor for RFS in all four breast cancer subtypes, namely luminal A (P = 0.006), luminal B (P = 0.001), HER-2 enriched (P = 0.039), and triple-negative breast cancer (P = 0.035).
CONCLUSIONS The AJCC response criteria represent a simple and easily reproducible tool for response evaluation of NAC patients and a useful clinical prognostic marker for RFS. These criteria also have a prognostic impact in all four breast cancer subtypes, including luminal A in which pCR has a limited role.
- 1622016
제1저자 윤창환,최영은, 차영륜 · 교신저자 김효수,채인호
, , , , , , , , ,
Diabetes-Induced Jagged1 Overexpression in Endothelial Cells Causes Retinal Capillary Regression in a Murine Model of Diabetes Mellitus: Insights Into Diabetic Retinopathy.Circulation. 2016;134(3):233-47.
PubMed IF 41.3 순환기내과Abstract
BACKGROUND Several mechanisms have been proposed to account for diabetes-induced microvasculopathy (DMV). Although Notch signaling was reported to be affected by glucose metabolism in endothelial cells during developmental angiogenesis, it has not been investigated in vascular remodeling of adult capillaries in relation to diabetes mellitus.
METHODS We induced diabetes mellitus in 8-week-old adult mice by intravenously administering streptozotocin. After 6 weeks, we harvested organs, including retina, heart, and skeletal muscle, and evaluated the capillaries with immunofluorescence and confocal microscopy. We modulated endothelial Notch signaling using chemical inhibitors in wild-type mice or transgenic mice, inducing conditional knockout of Jagged1 or Mib1.
RESULTS DMV was characterized by capillary remodeling, regression, and decreased density. Notch ligand Jagged1, but not δ-like ligand 4, was markedly increased in endothelial cells of diabetic mice. Using endothelium-specific Jagged1 knockdown mice, we found that blocking Jagged1 prevented DMV even under diabetic conditions. Furthermore, in the inducible endothelium-specific Jagged1 knockdown mice, blocking Jagged1 even at 4 weeks after the establishment of DMV could reverse it, leading to normalization of retinal vasculature. A search for downstream signals revealed that diabetes mellitus decreased the nuclear localization of Notch1 intracellular domain and reduced the expression of VE-cadherin and N-cadherin in endothelial cells. Chemical Notch inhibition phenocopied DMV in normal mice.
CONCLUSIONS Our findings indicate that diabetes mellitus induces Jagged1 overexpression and suppresses Notch signaling in endothelial cells, leading to DMV in adult mice. We conclude that dysregulated intercellular Notch signaling may be a novel mechanism of DMV.
- 1612016
제1저자 권지혜 · 교신저자 임종필
, , , , , , , , , , , ,
Disease Phenotype, Activity and Clinical Course Prediction Based on C-Reactive Protein Levels at Diagnosis in Patients with Crohn's Disease: Results from the CONNECT Study.Gut Liver. 2016;10(4):595-603.
PubMed IF 4.1 소화기내과Abstract
BACKGROUND/AIMS C-reactive protein (CRP) is an easily measured index of disease activity, but its ability to predict clinical course is controversial. We therefore designed a study to determine whether the CRP level at Crohn's disease (CD) diagnosis is a valuable indicator of the disease phenotype, activity, and clinical course.
METHODS We retrospectively analyzed 705 CD patients from 32 institutions. The patients were classified into two groups according to CRP level. The patients' demographic and clinical characteristics and their use of immunosuppressive or biological agents were recorded. Disease location and behavior, hospitalization, and surgery were analyzed.
RESULTS A high CRP was associated with younger age, steroid use, colonic or ileocolonic location, high CD activity index, and active inflammation at colonoscopy (p<0.001). As the disease progressed, patients with high CRP were more likely to exhibit strictures (p=0.027). There were significant differences in the use of 5-aminosalicylic acid, antibiotics, corticosteroids, azathioprine, and infliximab (p<0.001, p<0.001, p<0.001, p<0.001, and p=0.023, respectively). Hospitalization was also more frequent in patients with high CRP.
CONCLUSIONS The CRP level at diagnosis is useful for evaluating the phenotype, activity, and clinical course of CD. Closer follow-up strategies, with early aggressive treatment, could be considered for patients with high CRP.
- 1602016
제1저자 강시혁 · 교신저자 최의근
, , , , , , , ,
Underweight is a risk factor for atrial fibrillation: A nationwide population-based study.Int J Cardiol. 2016;215:449-56.
PubMed IF 3.3 순환기내과Abstract
BACKGROUND Obesity is a well-known risk factor for development of atrial fibrillation (AF). However, the impact of underweight on AF has not been previously recognized. We sought to determine the risk of AF in subjects with underweight in this study.
METHODS We analyzed clinical data from a total of 132,063 individuals with the age of 40years or older who received health care checkups arranged by the national insurance program between 2003 and 2004. Newly diagnosed nonvalvular AF was identified using claim data during a median follow-up duration of 9.0years.
RESULTS The mean body mass index (BMI) of patients was 23.9kg/m(2), and 3,323 individuals (2.5%) were classified as being underweight (BMI <18.5kg/m(2)). During the study period, 3,237 individuals (2.5%) developed AF. There was a U-shaped relationship between BMI and AF occurrence: Each 1.0kg/m(2) increase of BMI above 20kg/m(2) was associated with a 6% increased risk of AF (p<0.001), while each 1.0kg/m(2) lower BMI below 20kg/m(2) was associated with a 13% increased risk of AF (p<0.001) after multivariable adjustment. Underweight was significantly associated with 23% increased risk of AF, while obesity classes I and II were with 26% and 120% increased risk of AF, respectively. Excess risk of AF in the underweight was independent of thyroid disease, chronic lung disease, or history of malignancy, and was not attributable to cigarette smoking, low socioeconomic status, excessive physical activity, or heavy alcohol consumption.
CONCLUSION BMI has a U-shaped relationship with the risk of AF. Underweight was an independent risk factor for AF independent of confounding factors such as chronic lung disease and malignancy. These findings suggest that underweight is associated with biological effects that contribute to the development of AF.
- 1592016
제1저자 이춘수, 김윤기 · 교신저자 김효수
, , , , , , , ,
Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE-cadherin Phosphorylation.Sci Rep. 2016;6:29393.
PubMed IF 4.9 순환기내과Abstract
The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1α (SDF-1α), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1α)-blocker or Src-inhibitor. Disruption of endothelial cell-to-cell junctions in the immuno-fluorescence images correlated with the actual leakage of the endothelial monolayer in the transwell endothelial permeability assay. In the Miles assay, vascular leakage was observed in the ears into which SDF-1α was injected, and this effect was aggravated by DPP4-inhibitor. In the model of retinopathy of prematurity, DPP4-inhibitor increased not only retinal vascularity but also leakage. Additionally, in the murine diabetic retinopathy model, DPP4-inhibitor increased the phosphorylation of Src and VE-cadherin and aggravated vascular leakage in the retinas. Collectively, DPP4-inhibitor induced vascular leakage by augmenting the SDF-1α/CXCR4/Src/VE-cadherin signaling pathway. These data highlight safety issues associated with the use of DPP4-inhibitors.
- 1582016
제1저자 임우현,채인호 · 교신저자 김효수
, , , , , , , , , , , , , , , , , , , , , , ,
Comparison of dual antiplatelet therapy prescribed as one-pill versus two-pill regimen. A pooled analysis of individual patient data from the three MR-CAPCIS trials.Thromb Haemost. 2016;116(1):78-86.
PubMed IF 5.2 순환기내과Abstract
Fixed-dose combination (FDC) drugs can simplify the medication regimen and potentially improve adherence. However, evidence is lacking about the efficacy and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the three independent MR-CAPCIS trials were pooled and analysed. In those trials, subjects who had been treated with either dual antiplatelet therapy (DAPT) or aspirin alone after drug-eluting stent (DES) implantation were randomly assigned to one-pill or to two-pill DAPT group. Platelet reactivity was measured with VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks after treatment. In the present study, primary efficacy endpoint was changes in platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965 subjects were analysed. In prior clopidogrel and aspirin users, PRU was well maintained regardless of switching to either one-pill or two-pill DAPT (ΔPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7 in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between them (p=0.499). The incidence of high on-treatment platelet reactivity at eight weeks, defined as PRU≥235 in Western people, was 34.8 % in one-pill DAPT group and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU ≥275 in Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high platelet reactivity on clopidogrel were female gender, increasing age, and diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT showed similar efficacy to two-pill DAPT in terms of platelet reactivity in patients receiving DES in Korea.
서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.