SCI 발표논문

전체 4,588편

24282017

제1저자 정정화 · 교신저자 김진욱

, , , , , , ,
Development of a nomogram for screening of hepatitis B virus-associated hepatocellular carcinoma.
Oncotarget. 2017;8(63):106499-106510.

Abstract
Current strategy of hepatocellular carcinoma (HCC) surveillance evaluates individual risks of HCC for defining candidates for surveillance, but estimated risks are not utilized for clinical decision-making during actual screening. We sought to determine whether consideration of individual risks improve the performance of ultrasound (US)-based HCC screening in a real-world chronic hepatitis B (CHB) cohort. This single center retrospective cohort study analyzed 27,722 screening US tests from 4,175 consecutive CHB patients. Logistic regression analysis was performed to identify independent parameters predicting presence of HCC. A nomogram was built based on the independent predictors of HCC and compared with US-only screening by receiver operating characteristics analysis. The cost-effectiveness of the nomogram was assessed by decision curve analysis. HCC developed in 222 patients with the incidence of 0.769 per 1000 person-year during the median follow-up of 63 months. Age, sex, presence of cirrhosis, serum alpha-fetoprotein (AFP) levels and positive US test results were independent predictors of HCC presence. A nomogram based on these predictors showed higher C-statistics compared to US-only screening (0.960 vs. 0.731 and 0.935 vs. 0.691 for derivation and validation cohort, respectively; p < 0.001). Decision curve analysis showed higher net benefit of the HCC nomogram-guided screening model compared to US-only screening in the risk threshold range between 0 and 0.3. A nomogram composed of age, sex, presence of cirrhosis, serum AFP levels and US findings better predicted the presence of HCC compared to US-only screening in CHB on surveillance.
PubMed IF 5.168 소화기내과
24272017

제1저자 이지은 · 교신저자 김경민

, , , , , , , , , ,
Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: A cross-sectional observation.
Bone. 2017;105:269-275.

Abstract
Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1-L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.
PubMed IF 3.9 내분비대사내과
24262017

제1저자 송영신, 임정아 · 교신저자 박영주

, , , , , , , , , ,
Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer.
Eur J Endocrinol. 2017;177(6):465-473.

Abstract
OBJECTIVE Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer (FTC) over time have not been reported. Moreover, the prognostic effects of RAS and TERT promoter mutations in FTC have not been clearly elucidated. We investigated changes in the clinicopathological characteristics of patients with FTC over four decades, as well as the clinical significance of genetic mutations of FTC.
DESIGN AND METHODS This retrospective study included 690 patients with FTC who underwent thyroidectomy between 1973 and 2015 at the Seoul National University Hospital. In 134 samples, genetic tests for N/H/KRAS and TERT promoter mutations and PAX8/PPARγ rearrangement were performed.
RESULTS The age at diagnosis has increased (P < 0.001) in recent decades and extrathyroidal extension of the tumor has become less common (P = 0.033). Other clinicopathological characteristics and prognosis of FTC have not significantly changed. The prevalence of RAS mutations decreased (P = 0.042) over time, whereas that of TERT promoter mutations remained stable. RAS mutations were associated with distant metastasis and persistent disease, and TERT promoter mutations were associated with distant metastasis, advanced TNM stage, recurrence and disease-specific mortality. FTC patients with coexistent RAS and TERT promoter mutations showed a higher recurrence risk than those with only one mutation.
CONCLUSIONS The age at diagnosis of FTC and the frequency of extrathyroidal extension have changed over four decades. Moreover, the prevalence of RAS mutations decreased. RAS and TERT promoter mutations may be associated with poor clinical outcomes in FTC, especially when the two mutations coexist.
PubMed IF 6.7 내분비대사내과
24252017

제1저자 홍아람, 김정희 · 교신저자 김상완

, , , , , , , , ,
Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice.
Eur J Endocrinol. 2017;177(6):475-483.

Abstract
OBJECTIVE Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years.
DESIGN AND METHODS This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines.
RESULTS The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study.
CONCLUSIONS We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.
PubMed IF 6.7 내분비대사내과
24242017

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , , ,
Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017;18(12):1637-1651.

Abstract
BACKGROUND Olaparib combined with paclitaxel has previously shown a significant improvement in overall survival versus placebo plus paclitaxel as second-line therapy in a phase 2 study in Asian patients with advanced gastric cancer, especially in those with ataxia-telangiectasia mutated protein (ATM)-negative tumours. Here, we report the primary efficacy and safety analyses from a subsequent phase 3 trial.
METHODS This double-blind, randomised, placebo-controlled, phase 3 study (GOLD) recruited Asian patients aged 18 years or older (≥20 years if Japanese) with advanced gastric cancer that had progressed following, or during, first-line chemotherapy. Patients were randomly assigned (1:1) to receive oral olaparib (100 mg twice daily) plus paclitaxel (80 mg/m² intravenously) or matching placebo plus paclitaxel. Randomisation was done through an interactive voice response system and no stratification factors were used. Patients and investigators were masked to treatment allocation. Two co-primary populations were assessed: the overall population of all patients and patients whose tumours were ATM-negative (identified after randomisation, before the data cutoff date, March 28, 2016). The primary endpoint in both populations was overall survival (defined as the time from the date of randomisation until death from any cause before data cutoff); a significant difference was defined as p<0·025. Efficacy was assessed in the intention-to-treat populations and safety in patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT01924533 (study ID, D081BC00004), and is ongoing but no longer recruiting participants.
FINDINGS Between Sept 3, 2013, and March 28, 2016, 643 patients were enrolled from 58 study sites in hospitals and medical centres in China, Japan, South Korea, and Taiwan. 525 eligible patients were randomly assigned: 263 to receive olaparib plus paclitaxel and 262 to receive placebo plus paclitaxel. 94 patients were determined to have ATM-negative tumours before unmasking for the primary analysis (48 in the olaparib plus paclitaxel group and 46 in the placebo plus paclitaxel group). Overall survival did not differ between treatment groups in the overall patient population (median overall survival 8·8 months [95% CI 7·4-9·6] in the olaparib group vs 6·9 months [6·3-7·9] in the placebo group; HR 0·79 [97·5% CI 0·63-1·00]; p=0·026) or in the ATM-negative population (12·0 months [7·8-18·1] vs 10·0 months [6·4-13·3]; 0·73 [0·40-1·34]; p=0·25). In the overall patient population, the most common grade 3 or worse adverse events in the olaparib plus paclitaxel group were neutropenia (78 [30%] of 262 patients), leucopenia (42 [16%]), and decreased neutrophil count (40 [15%]); in the placebo plus paclitaxel group, they were neutropenia (59 [23%] of 259 patients), leucopenia (27 [10%]), and decreased white blood cell count (21 [8%]). Adverse events with an outcome of death causally related to study treatment (according to investigator assessment) were reported in two patients: liver injury in one patient (<1%) in the olaparib plus paclitaxel group and cardiac failure in one patient (<1%) in the placebo plus paclitaxel group.
INTERPRETATION The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in the overall or ATM-negative population of Asian patients with advanced gastric cancer. The study generated informative efficacy and safety data regarding the use of olaparib in combination with a chemotherapeutic agent and provides a foundation for future studies in this difficult-to-treat patient population.
FUNDING AstraZeneca.
PubMed IF 33.7 혈액종양내과
24232017

제1저자 장경민 · 교신저자 김학령

, , , , , , , , ,
Additional Value of Brachial-Ankle Pulse Wave Velocity to Single-Photon Emission Computed Tomography in the Diagnosis of Coronary Artery Disease.
J Atheroscler Thromb. 2017;24(12):1249-1257.

Abstract
AIM The aim of this study was to investigate whether information on arterial stiffness can improve the value of single-photon emission computed tomography (SPECT) in the detection of obstructive coronary artery disease (CAD).
METHODS A total of 233 patients (age: 62.2±10.8 years, 60.3% males) with detected ischemia on SPECT undergoing invasive coronary angiography (ICA) and brachial-ankle pulse wave velocity (baPWV) measurement within a month was retrospectively reviewed.
RESULTS Of the 233 patients, 190 (81.5%) had obstructive CAD (≥50% luminal stenosis). The difference in baPWV according to the presence of obstructive CAD was significant in patients in the mild ischemia group [summed stress score (SSS): 4-8] (1,770±364 cm versus 1,490±328 cm, p＜0.001) but not in the moderate (SSS: 9-13) or severe (SSS: ≥14) ischemia groups (p＞0.05 for each). Receiver operating characteristic curve analyses showed that the diagnostic value of baPWV for obstructive CAD was significant only in patients in the mild ischemia group (area under curve: 0.714; p=0.001) but not in the moderate or severe ischemia groups (p＞0.05 for each). Adding information on baPWV to SPECT results and clinical parameters significantly increased diagnostic accuracy in the detection of obstructive CAD in patients with mild ischemia (integrated discrimination improvement p=0.006) but not in those with moderate or severe ischemia on SPECT (p＞0.05 for each).
CONCLUSIONS The results of this study suggest that baPWV may have additional value to SPECT for the detection of obstructive CAD, especially in patients with mild ischemia on SPECT.
PubMed IF 3.4 순환기내과
24222017

제1저자 박진주 · 교신저자 최동주

, , , , , , , , , , , , , ,
Short and long-term prognostic value of hyponatremia in heart failure with preserved ejection fraction versus reduced ejection fraction: An analysis of the Korean Acute Heart Failure registry.
Int J Cardiol. 2017;248:239-245.

Abstract
BACKGROUND Hyponatremia is a well-known risk factor for worse outcomes in heart failure (HF) patients. The impact of hyponatremia according to the ejection fraction (EF) is unclear. We evaluated the prognostic value of hyponatremia according to HF type.
METHODS AND RESULTS The Korea Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients. Hyponatremia was defined as serum sodium level<135mmol/L at hospital admission. HF with preserved and reduced ejection fraction were defined as an LVEF ≥50% and LVEF ≤40%, respectively. Among 5103 patients with available EF, 2088 (60%) had HFrEF, and 1284 (25%) had HFpEF. There was no difference in serum sodium level between the groups (HFrEF: 137.4±4.7mmol/L vs. HFpEF: 137.5±5.0mmol/L, P=0.710). Hyponatremic patients had higher in-hospital mortality or urgent heart transplantation in all (11.3% vs. 4.5%, P<0.001), in HFrEF (13.1% vs. 4.9%, P<0.001), and in HFpEF (6.0% vs. 1.9%, P<0.001). After adjustment for significant covariates, hyponatremia was associated with 1.5 fold increased risk for 1-year post-discharge death in the HFrEF group (HR, 1.52; 95% CI, 1.24-1.86), but not in the HFpEF group (HR, 1.16; 95% CI, 0.84-1.61). During admission, the sodium status changed in 22% of the patients and the discharge sodium status had greater prognostic value.
CONCLUSIONS Hyponatremia is independent of HF type. Hyponatremia is a significant risk factor for adverse in-hospital outcomes; however its long-term prognostic value is only limited to patients with HFrEF, but not for those with HFpEF.
PubMed IF 3.3 순환기내과
24212017

제1저자 강시혁 · 교신저자 최동주

, , , , , , ,
Risk of stroke in congestive heart failure with and without atrial fibrillation.
Int J Cardiol. 2017;248:182-187.

Abstract
BACKGROUND Heart failure has been associated with an increased risk for ischemic stroke. This study estimated the risk of stroke and thromboembolism for patients with congestive heart failure (CHF) in the context of the general population, especially compared to those with atrial fibrillation (AF).
METHODS Data of patients discharged alive from 2003 to 2012 were extracted from the National Health Insurance Corporation sample cohort. Subjects were classified into control (n=90,277), CHF (n=4533), AF (n=1187), and CHF plus AF (n=1213) groups.
RESULTS CHF was associated with an increased risk for ischemic stroke, which was significant after various adjustment models. Annualized stroke risk was 0.54 (0.52-0.57) per 100 person-years for the control group, 2.00 (1.79-2.21) for the CHF group, 2.27 (1.84-2.69) for the AF group, and 2.87 (2.38-3.36) for the CHF plus AF group. The CHA₂DS₂-VASc scoring schema had a moderate discriminatory value for stroke risk in patients with CHF as well as in AF. The risk of stroke for the CHF group was comparable to that of the AF group when stratified according to the CHA₂DS₂-VASc scores. Those with CHA₂DS₂-VASc score of 0 or 1 were at low risk for stroke for both CHF and AF.
CONCLUSION Patients with CHF are at increased risk for ischemic stroke and thromboembolism. This study showed that the CHA₂DS₂-VASc schema can help stratify stroke risk for individual CHF patients. Stroke is a frequent complication among patients with CHF; therefore, safe and effective strategies to prevent stroke are needed.
PubMed IF 3.3 순환기내과
24202017

제1저자 최의근 · 교신저자 Peng-Sheng Chen

, , ,
Ganglionated plexi as neuromodulation targets for atrial fibrillation.
J Cardiovasc Electrophysiol. 2017;28(12):1485-1491.

Abstract
The autonomic nervous system plays an important role in the genesis of atrial fibrillation and is one of the candidate targets for atrial fibrillation therapy. This review focuses on the role of the autonomic nervous system in atrial fibrillation development and discusses the results of the ganglionated plexi catheter and surgical ablation in preclinical and clinical studies. The heart is innervated by the extrinsic and intrinsic autonomic nervous systems. The intrinsic autonomic nervous system consists of multiple ganglionated plexi and axons, which innervate the neighboring atrial myocardium and control their electrophysiological properties. Abnormal autonomic innervation has been observed in an animal model of atrial fibrillation and in humans. Direct recordings of autonomic nerve activity in canine models showed that atrial tachyarrhythmia episodes were invariably preceded by intrinsic cardiac autonomic nerve activity, thus supporting the importance of intrinsic cardiac autonomic nerve activity as the triggers for atrial tachyarrhythmia. Targeting ganglionated plexi with catheter ablation improves the outcomes of paroxysmal atrial fibrillation ablation in addition to pulmonary vein antrum isolation. Ablation of ganglionated plexi alone without pulmonary vein isolation is also useful in controlling paroxysmal atrial fibrillation in some patients. However, surgical ganglionated plexi ablation in patients with a large left atrium, persistent atrial fibrillation, and/or a history of prior catheter ablation does not result in additional benefits. These different outcomes suggest that ganglionated plexi ablation is effective in managing patients with paroxysmal atrial fibrillation, but its effects in patients with persistent atrial fibrillation and advanced atrial diseases might be limited.
PubMed IF 2.4 순환기내과
24192017

제1저자 유미연 · 교신저자 진호준

, , ,
Short-term anti-proteinuric effect of tacrolimus is not related to preservation of the glomerular filtration rate in IgA nephropathy: A 5-year follow-up study.
PLoS One. 2017;12(11):e0188375.

Abstract
BACKGROUND The immunosuppressive drug tacrolimus has the short-term effect of reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN). Our study investigated the effects on proteinuria and kidney function after discontinuation of tacrolimus.
METHODS Patients with biopsy-proven IgAN were included in the study and randomly divided into two treatment groups. There was a corresponding control group for each treatment group. The first group included patients treated with tacrolimus (Tac vs non-Tac group) and the second group included patients with a renin angiotensin system blocker (RASi vs non-RASi group). The Tac group received treatment for up to 16 weeks, with the administration of tacrolimus being ceased at the final visit (trial phase). We tracked the patients at 12, 24, 52, and 240 weeks (observational phase). The primary outcomes examined were the percentage change (from the trial phase to the observational phase) of time-averaged proteinuria (TA-proteinuria; g/g creatinine [cr]) and the estimated glomerular filtration rate (eGFR). Time-averaged proteinuria was defined as the average of urine protein to creatinine ratio (UPCR), measured every 3 months during both the trial and observational phases of the study.
RESULTS A significant reduction in UPCR was observed in the Tac group compared to non-Tac group at the 4 and 8 week visits during the trial phase (p = 0.023 and p = 0.003, respectively). However, the difference between the Tac group and non-Tac group was not evident in the other review periods, estimated by linear mixed effect model. The percentage change in TA-proteinuria was greater in the Tac group than that in the corresponding control group (116 ± 96% vs. 63 ± 239%, p = 0.004). Therefore, during the observational phase, TA-proteinuria was not significantly different between the Tac group and the non-Tac group (1.150 ± 0.733 g/g cr vs. 1.455 ± 2.017 g/g cr, p = 0.775). The levels of eGFR throughout the observational phase were not significantly different between the two groups. Furthermore, the mean rate of eGFR change throughout both phases of the study was -6.4 ± 5.9 mL/min/1.73 m2/year in the non-Tac group and -5.4 ± 7.9 mL/min/1.73 m2/year in the Tac group (p = 0.988).
CONCLUSION The anti-proteinuric effect of tacrolimus was promptly reversed 3 months after discontinuing the drug. The use of tacrolimus for a short period of time for patients with IgAN temporarily reduces proteinuria, but the data showed no long-term efficacy regarding proteinuria reduction and improvement of renal function.
PubMed IF 2.8 신장내과
24182017

제1저자 김경민 · 교신저자 임수

, , , , , ,
Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report.
Cardiovasc Diabetol. 2017;16(1):146.

Abstract
BACKGROUND The cardiovascular benefits of statins have been proven, but their effect on circulation in small vessels has not been examined fully. We investigated the effect of 20 mg rosuvastatin on biomarkers, including paraoxonase-1 (PON-1) and asymmetric dimethylarginine (ADMA), and on microvascular reactivity.
METHOD We enrolled 20 dyslipidemic patients with type 2 diabetes and 20 age- and body mass index (BMI)-matched healthy controls. Rosuvastatin (20 mg/day) was given to the patient group for 12 weeks. Biochemical parameters, including PON-1 and ADMA, were compared between the patient and control groups, and before and after rosuvastatin treatment in the patient group. Fasting and 2 h postprandial levels of PON-1 and ADMA after mixed-meal challenge were also compared. Microvascular reactivity in a peripheral artery was examined using laser Doppler flowmetry.
RESULTS The respective mean ± standard deviation of age and BMI were 50.1 ± 3.8 year and 25.8 ± 3.7 kg/m² in the patients and 50.2 ± 3.2 year and 25.4 ± 3.4 kg/m² in the controls. The patient group had worse profiles of cardiometabolic biomarkers, including PON-1 and ADMA, than the controls. In the patients treated with 20 mg rosuvastatin, low-density lipoprotein (LDL)-cholesterol decreased from 147.2 ± 26.5 to 68.3 ± 24.5 mg/dL and high-density lipoprotein (HDL)-cholesterol increased from 42.4 ± 5.2 to 44.7 ± 6.2 mg/dL (both P < 0.05). Both fasting and 2 h postprandial levels of PON-1 increased and those of ADMA decreased after treatment with rosuvastatin for 12 weeks. The changes in postprandial levels of both biomarkers were greater than those after fasting. Microcirculation assessed as reactive hyperemia in the patients after an ischemic challenge increased significantly from 335.3 ± 123.4 to 402.7 ± 133.4% after rosuvastatin treatment. The postprandial changes in the biomarkers were significantly associated with improvement of microvascular reactivity.
CONCLUSIONS Rosuvastatin treatment for 12 weeks improved microvascular reactivity with concomitant beneficial changes in the postprandial levels of PON-1 and ADMA. These results suggest that rosuvastatin improves the postprandial cardiometabolic milieu in type 2 diabetes. Trial registration ClinicalTrials.gov: NCT02185963 (July 7, 2014).
PubMed IF 15.6 내분비대사내과
24172017

제1저자 이윤빈, 최종호 · 교신저자 윤정환, 김기진

, , , , , ,
Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation.
Stem Cells Int. 2017;2017:5180579.

Abstract
In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33-a posttranscriptional regulator of CPT1A-in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production-an indicator of mitochondrial function-was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.
PubMed IF 3.6 소화기내과
24162017

제1저자 김현지 · 교신저자 강시혁

, , , , , , , , , ,
Cardiovascular Effects of Long-Term Exposure to Air Pollution: A Population-Based Study With 900 845 Person-Years of Follow-up.
J Am Heart Assoc. 2017;6(11):JAHA.117.007170.

Abstract
BACKGROUND Studies have shown that long-term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter [PM_2.5]) increases the risk of all-cause and cardiovascular mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long-term exposure to air pollution among residents of Seoul, Korea.
METHODS AND RESULTS Healthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person-years). The risk of major cardiovascular events increased with higher mean concentrations of PM_2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29-1.43) per 1 μg/m³ PM_2.5. Other pollutants including PM_2.5-10 of CO, SO₂, and NO₂, but not O₃, were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus.
CONCLUSIONS This large-scale population-based study demonstrated that long-term exposure to air pollution including PM_2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor.
PubMed IF 6 순환기내과
24152017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , ,
Exploring Coronary Circulatory Response to Stenosis and Its Association With Invasive Physiologic Indexes Using Absolute Myocardial Blood Flow and Coronary Pressure.
Circulation. 2017;136(19):1798-1808.

Abstract
BACKGROUND Although invasive physiological assessment for coronary stenosis has become a standard practice to guide treatment strategy, coronary circulatory response and changes in invasive physiological indexes, according to different anatomic and hemodynamic lesion severity, have not been fully demonstrated in patients with coronary artery disease.
METHODS One hundred fifteen patients with left anterior descending artery stenosis who underwent both ¹³N-ammonia positron emission tomography and invasive physiological measurement were analyzed. Myocardial blood flow (MBF) measured with positron emission tomography and invasively measured coronary pressures were used to calculate microvascular resistance and stenosis resistance.
RESULTS With progressive worsening of angiographic stenosis severity, both resting and hyperemic transstenotic pressure gradient and stenosis resistance increased (P<0.001 for all) and hyperemic MBF (P<0.001) and resting microvascular resistance (P=0.012) decreased. Resting MBF (P=0.383) and hyperemic microvascular resistance (P=0.431) were not changed and maintained stable. Both fractional flow reserve and instantaneous wave-free ratio decreased as angiographic stenosis severity, stenosis resistance, and transstenotic pressure gradient increased and hyperemic MBF decreased (all P<0.001). When the presence of myocardial ischemia was defined by both low hyperemic MBF and low coronary flow reserve, the diagnostic accuracy of fractional flow reserve and instantaneous wave-free ratio did not differ, regardless of cutoff values of hyperemic MBF and coronary flow reserve.
CONCLUSIONS This study demonstrated how the coronary circulation changes in response to increasing coronary stenosis severity using ¹³N-ammonium positron emission tomography-derived MBF and invasively measured pressure data. Currently used resting and hyperemic pressure-derived invasive physiological indexes have similar patterns of relationships to the different anatomic and hemodynamic lesion severities.
CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01366404.
PubMed IF 41.3 순환기내과
24142017

제1저자 박연희, 임석아 · 교신저자 정경해

, , , , , , , , , , , , , , , , , , ,
Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer.
Eur J Cancer. 2017;86:385-393.

Abstract
BACKGROUND Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel.
PATIENTS AND METHODS This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate.
RESULTS A total of 118 patients (median age: 50, 24-66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. The mean number of metastatic sites was 3 (range 1-8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (P = 0.457). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2-32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001).
CONCLUSION EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity.
TRIAL REGISTRATION KCSG BR13-11; ClinicalTrials.gov, NCT02263495.
PubMed IF 7.9 혈액종양내과
24132017

제1저자 김형진 · 교신저자 김범석, 박창민

, , , , , , , ,
The prognostic value of CT radiomic features for patients with pulmonary adenocarcinoma treated with EGFR tyrosine kinase inhibitors.
PLoS One. 2017;12(11):e0187500.

Abstract
PURPOSE To determine if the radiomic features on CT can predict progression-free survival (PFS) in epidermal growth factor receptor (EGFR) mutant adenocarcinoma patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) and to identify the incremental value of radiomic features over conventional clinical factors in PFS prediction.
METHODS In this institutional review board-approved retrospective study, pretreatment contrast-enhanced CT and first follow-up CT after initiation of TKIs were analyzed in 48 patients (M:F = 23:25; median age: 61 years). Radiomic features at baseline, at 1st first follow-up, and the percentage change between the two were determined. A Cox regression model was used to predict PFS with nonredundant radiomic features and clinical factors, respectively. The incremental value of radiomic features over the clinical factors in PFS prediction was also assessed by way of a concordance index.
RESULTS Roundness (HR: 3.91; 95% CI: 1.72, 8.90; P = 0.001) and grey-level nonuniformity (HR: 3.60; 95% CI: 1.80, 7.18; P<0.001) were independent predictors of PFS. For clinical factors, patient age (HR: 2.11; 95% CI: 1.01, 4.39; P = 0.046), baseline tumor diameter (HR: 1.03; 95% CI: 1.01, 1.05; P = 0.002), and treatment response (HR: 0.46; 95% CI: 0.24, 0.87; P = 0.017) were independent predictors. The addition of radiomic features to clinical factors significantly improved predictive performance (concordance index; combined model = 0.77, clinical-only model = 0.69, P<0.001).
CONCLUSIONS Radiomic features enable PFS estimation in EGFR mutant adenocarcinoma patients treated with first-line EGFR TKIs. Radiomic features combined with clinical factors provide significant improvement in prognostic performance compared with using only clinical factors.
PubMed IF 2.8 혈액종양내과
24122017

제1저자 홍준식 · 교신저자 김석진

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Improved prognostic stratification using NCCN- and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma.
Oncotarget. 2017;8(54):92171-92182.

Abstract
The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.
PubMed IF 5.168 혈액종양내과
24112017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Clinical Relevance of 18F-Sodium Fluoride Positron-Emission Tomography in Noninvasive Identification of High-Risk Plaque in Patients With Coronary Artery Disease.
Circ Cardiovasc Imaging. 2017;10(11):CIRCIMAGING.117.006704.

Abstract
BACKGROUND ¹⁸F-sodium fluoride (¹⁸F-NaF) positron-emission tomography has been introduced as a potential noninvasive imaging tool to identify plaques with high-risk characteristics in patients with coronary artery disease. We sought to evaluate the clinical relevance of ¹⁸F-NaF uptake using optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography in patients with coronary artery disease.
METHODS AND RESULTS The target population consisted of 51 prospectively enrolled patients (93 stenoses) who underwent ¹⁸F-NaF positron-emission tomography before invasive coronary angiography. ¹⁸F-NaF uptake was compared with IVUS- and OCT-derived plaque characteristics. In the coronary computed tomography angiography subgroup (46 lesions), qualitative lesion characteristics were compared between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative plaques using adverse plaque characteristics. The plaques with ¹⁸F-NaF uptake showed significantly higher plaque burden, more frequent posterior attenuation and positive remodeling in IVUS, and significantly higher maximum lipid arc and more frequent microvessels in OCT (all P<0.05). There were no differences in minimum lumen area and area of calcium between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative lesions. Among 51 lesions with ¹⁸F-NaF-positive uptake, 48 lesions (94.1%) had at least one of high-risk characteristics. The ¹⁸F-NaF tissue-to-background ratio in plaques with high-risk characteristics was significantly higher than in those without (1.09 [95% confidence interval, 0.85-1.34] versus 0.62 [95% confidence interval, 0.42-0.82], P<0.001 for IVUS definition; 0.76 [95% confidence interval, 0.54-0.98] versus 0.42 [95% confidence interval, 0.21-0.62], P=0.014 for OCT definition). Among the 15 lesions that met both IVUS- and OCT-defined criteria for high-risk plaque, 14 (93.3%) showed ¹⁸F-NaF-positive uptake. There was no difference in the prevalence of plaques with any adverse plaque characteristics between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative plaques in the coronary computed tomography angiography subgroup (85.2% versus 78.9%; P=0.583).
CONCLUSIONS This study's results suggest that ¹⁸F-NaF positron-emission tomography can be a useful noninvasive diagnostic tool to identify and localize plaque with high-risk characteristics.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02388412.
PubMed IF 9.1 순환기내과
24102017

제1저자 이태민 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , ,
Predictors and Long-Term Clinical Outcome of Longitudinal Stent Deformation: Insights From Pooled Analysis of Korean Multicenter Drug-Eluting Stent Cohort.
Circ Cardiovasc Interv. 2017;10(11):CIRCINTERVENTIONS.117.005518.

Abstract
BACKGROUND There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication.
METHODS AND RESULTS A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute). QCA was performed to analyze differences of stent length between immediate post-deployment and final post-procedure. Independent factors associated with LSD were identified. Clinical outcomes at 3 years were compared between those with and without QCA-based LSD. The frequency of QCA-based LSD was 1.12% (82 cases). Nine of these cases were angiographically overt. Left main or ostial lesion, bifurcation treatment with provisional side branch stenting or ballooning, additional downstream intervention of a distal lesion, intravascular ultrasound use, and adjunctive post-dilatation were independently associated with QCA-based LSD. The type of stent was not associated with QCA-based LSD. Rates of target lesion failure were nominally higher in lesions with QCA-based LSD than in those without (8.97% versus 5.88%; hazard ratio, 1.415; 95% confidence interval, 0.631-3.175; P=0.399).
CONCLUSIONS LSD is uncommon with contemporary drug-eluting stents, regardless of the type of stent platform. LSD is mainly associated with procedural factors, especially with additional downstream procedures which require the passage of devices through the stent. Careful manipulation of poststent imaging or procedural devices is required to prevent LSD. More data are needed to clarify the impact of LSD on clinical events.
PubMed IF 7.2 순환기내과
24092017

제1저자 Tatiana T, 이동화 · 교신저자 임수

, , , , , , ,
Effectiveness of a Smartphone Application for the Management of Metabolic Syndrome Components Focusing on Weight Loss: A Preliminary Study.
Metab Syndr Relat Disord. 2017;15(9):465-473.

Abstract
BACKGROUND There are inconsistent results for the effectiveness of using smartphone applications (apps) or websites on weight loss. We investigated the efficacy of a smartphone intervention using a designated app that utilizes a lifestyle intervention-focused approach, including a human coaching element, toward weight loss in overweight or obese Korean adults.
METHODS One hundred four adults aged 20-60 years with a body mass index ≥23 kg/m², who signed up for a smartphone program for weight loss (using the Noom app), were recruited. Participants received an in-person orientation about the study and app use, and a baseline blood sample was obtained. The in-app intervention with daily behavior and nutrition education content and coaching lasted 15 weeks. The primary endpoint of the study was a change in weight. The secondary endpoints were changes in metabolic risk factors such as blood pressure, waist circumference, and glucose and lipid profiles. Body composition changes were also assessed, and body weight at 52 weeks was measured to ascertain long-term effects.
RESULTS Participants showed a clinically significant weight loss effect of -7.5% at the end of the 15-week program (P < 0.001), and at a 52-week follow-up, a weight loss effect of -5.2% was maintained. At 15 weeks, percent body fat and visceral fat decreased by -6.0 ± 5.4% and -3.4 ± 2.7 kg, respectively (both P < 0.001). Fasting glucose level also decreased significantly by -5.7 ± 14.6 mg/dL at 15 weeks. Lipid parameters showed significant improvements, except for high-density lipoprotein cholesterol. The frequency of logging meals and exercise was associated with body fat loss.
CONCLUSIONS This advanced smartphone app was a useful tool to maintain weight loss in overweight or obese people.
PubMed IF 1.6 내분비대사내과
24082017

제1저자 최윤진 · 교신저자 이동호

, , , , , , , , , , , , , , , , , , , , ,
Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.
J Korean Med Sci. 2017;32(11):1807-1813.

Abstract
This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670).
PubMed IF 3.2 소화기내과
24072017

제1저자 이성우 · 교신저자 진호준

, , , , , , , ,
Is Frailty a Modifiable Risk Factor of Future Adverse Outcomes in Elderly Patients with Incident End-Stage Renal Disease?
J Korean Med Sci. 2017;32(11):1800-1806.

Abstract
Little is known about the clinical significance of frailty and changes of frailty after dialysis initiation in elderly patients with end-stage renal disease (ESRD). We prospectively enrolled 46 elderly patients with incident ESRD at a dialysis center of a tertiary hospital between May 2013 and March 2015. Frailty was assessed by using a comprehensive geriatric assessment protocol and defined as a multidimensional frailty score of ≥ 10. The main outcome was the composite of all-cause death or cardiovascular hospitalization, as determined in June 2016. The median age of the 46 participants was 71.5 years, and 63.0% of them were men. During the median 17.7 months follow-up, the rate of composite outcome was 17.4%. In multivariate logistic regression analysis, after adjusting for age, sex, diabetes, body mass index (BMI), and time of predialytic nephrologic care, female sex, and increased BMI were associated with increased and decreased odds of frailty, respectively. In multivariate Cox proportional hazards analysis, after adjusting for age, sex, diabetes, BMI, and time of predialytic nephrologic care, frailty was significantly associated with the composite adverse outcome. In repeated frailty assessments, the multidimensional frailty score significantly improved 12 months after the initiation of dialysis, which largely relied on improved nutrition. Therefore, frailty needs to be assessed for risk stratification in elderly patients with incident ESRD.
PubMed IF 3.2 신장내과
24062017

제1저자 이해영 · 교신저자 오병희

, , , , , ,
24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension.
Korean J Intern Med. 2017;32(6):1025-1036.

Abstract
BACKGROUND/AIMS Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension.
METHODS This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ≥ 135/85 mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index.
RESULTS At week 8, the mean 24-hour SBP values significantly decreased in both groups; -10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and -5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs.
CONCLUSIONS In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.
PubMed IF 2.2 순환기내과
24052017

제1저자 이현정 · 교신저자 최의근

, , , , , , , ,
Cirrhosis is a risk factor for atrial fibrillation: A nationwide, population-based study.
Liver Int. 2017;37(11):1660-1667.

Abstract
BACKGROUND & AIMS Information is lacking regarding whether cirrhosis is associated with atrial fibrillation development. We aimed to investigate the incidence and clinical significance of atrial fibrillation in cirrhotic patients.
METHODS Cirrhotic patients (n=3596; mean age, 54.7±12.3 years; male, 72.5%) without previous atrial fibrillation were selected from the Korean National Health Insurance Service National Sample Cohort database between 2004 and 2008. Age- and sex-matched controls (n=17 980) were randomly sampled in a 5:1 ratio from non-cirrhotic individuals. Both cohorts were followed up for incident atrial fibrillation and death until 2013.
RESULTS During 9 years of follow-up, atrial fibrillation was newly detected in 113 (3.1%) cirrhosis patients and 385 (2.1%) controls (incidence: 3.48 and 2.16 per 1000 person-years respectively). Cirrhotic patients were at higher risk for atrial fibrillation development compared to controls (hazard ratio, 1.46; 95% confidence interval, 1.18-1.80) after multivariate adjustment. On subgroup analysis, cirrhosis increased the risk for atrial fibrillation, especially in younger (age younger than 65 years) men without comorbidities (CHA₂ DS₂ -VASc score, 0). Cirrhotic patients showed increased overall mortality compared to controls (hazard ratio, 4.80; 95% confidence interval, 4.47-5.15) as well as increased cardiovascular mortality (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75). However, there was no significant association between development of atrial fibrillation and increased mortality in cirrhosis patients (P=.188 and .260).
CONCLUSIONS Cirrhosis was an independent risk factor for atrial fibrillation development, especially in younger, otherwise healthy men, stressing the importance of cardiac assessment in cirrhotic patients. Meanwhile, atrial fibrillation development in cirrhosis patients was not associated with increased mortality.
PubMed IF 6.2 순환기내과
24042017

제1저자 강성희, 이윤빈 · 교신저자 이정훈

, , , , , , , , , , , , ,
Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.
Aliment Pharmacol Ther. 2017;46(9):845-855.

Abstract
BACKGROUND Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth.
AIM To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications.
METHODS We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding.
RESULTS In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338).
CONCLUSIONS In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
PubMed IF 6.8 소화기내과
24032017

제1저자 이해영 · 교신저자 김재중

, , ,
Initial Report of the Korean Organ Transplant Registry (KOTRY): Heart Transplantation.
Korean Circ J. 2017;47(6):868-876.

Abstract
BACKGROUND AND OBJECTIVES The Korean Organ Transplant Registry (KOTRY), which was the first national transplant registry in Korea, was founded by the Korean Society for Transplantation and the Korean Center for Disease Control in 2014. Here, we present the initial report of the Korean Heart Transplant Registry.
METHODS A total of 183 heart transplantation (HTPL) patients performed at 4 nationally representative hospitals were collected from April 2014 to December 2015. We analyzed donor and recipient characteristics, treatment patterns, and immediate post-transplantation outcomes.
RESULTS One hundred and eighty-three patients were enrolled. The mean age of the patients was 50.5±13.5 years. The mean age of the male recipients was 4 years greater than that of the female recipients (51.7±13.3 years vs. 47.9±13.7 years, p<0.050). The mean age of donors was more than 12 years younger than that of heart recipients (37.6±10.1 years). Dilated cardiomyopathy was the predominant cause (69%) of heart failure in recipients, followed by ischemic heart diseases (14%) and valvular heart disease (4%). Rejection episodes were most frequent in the 1-6-month period after transplantation (48%), and rarely required intensive treatment. Infection episodes were most frequent <1 month after transplantation (66%) and bacterial and viral infections were equally reported. The 1-year survival rate was 91.6% and most mortality cases occurred during the perioperative period within 1 month after transplantation.
CONCLUSION With the establishment of the KOTRY in 2014, it is now possible to present nationwide epidemiological data for HTPL in Korea for the first time. The KOTRY is the first national HTPL registry in Korea, and will continue until 2023.
PubMed IF 3.4 순환기내과
24022017

제1저자 Gyojeong Gu · 교신저자 이해영

, , , ,
Zebrafish Larvae Model of Dilated Cardiomyopathy Induced by Terfenadine.
Korean Circ J. 2017;47(6):960-969.

Abstract
BACKGROUND AND OBJECTIVES Dilated cardiomyopathy can be the end-stage of severe cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly and heart failure (HF). Although a wide variety of animal models are available to study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy with non-invasive, simple, and large screening methods.
METHODS We developed a dilated cardiomyopathy model in zebrafish larvae using short duration terfenadine, a known cardiotoxic drug that induces ventricular size dilation. Fractional shortening of zebrafish hearts was calculated.
RESULTS We treated zebrafish with 5 to 10 μM terfenadine for 24 hours. In terfenadine-treated zebrafish, blood frequently pooled and clotted in the chamber, and circulation was remarkably reduced. Atria and ventricles were swollen, and fluid was deposited around the heart, mimicking edema. Cardiac contractility was significantly reduced, and ventricular area was significantly enlarged. Heart rate was markedly reduced even after terfenadine withdrawal. Acridine orange staining also showed that terfenadine increased cardiomyocyte apoptosis. A significant increase of natriuretic peptide B (NPPB) mRNA was found in terfenadine-treated zebrafish. A low dose of terfenadine (5-10 μM) did not show mortality in short-term treatment (24 hours). However, moderate dose (35-45 μM) terfenadine treatment reduced zebrafish survival within 1 hour.
CONCLUSION With advantages of rapid sample preparation procedure and transparent observation of the live heart, this model can potentially be applied to large-scale drug screening and toxicity assays for non-ischemic HF.
PubMed IF 3.4 순환기내과
24012017

제1저자 차명진 · 교신저자 최의근

, , , , , ,
Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.
Stroke. 2017;48(11):3040-3048.

Abstract
BACKGROUND AND PURPOSE There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients.
METHODS Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA₂DS₂-VASc score ≥2) between 2014 and 2015.
RESULTS NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH.
CONCLUSIONS In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.
PubMed IF 11.1 순환기내과
24002017

제1저자 최원묵 · 교신저자 유수종

, , , , , , , , , , , ,
A model to estimate survival in ambulatory patients with hepatocellular carcinoma: Can it predict the natural course of hepatocellular carcinoma?
Dig Liver Dis. 2017;49(11):1273-1279.

Abstract
BACKGROUND Several hepatocellular carcinoma (HCC) staging systems are available including the newly developed staging system, the Model to Estimate Survival in Ambulatory HCC patients (MESIAH); however, whether these staging systems could predict the natural course of HCC is largely unknown.
METHODS 1013 patients with history of HCC treatment and 111 patients without any history of treatment till death or last follow-up at a single tertiary hospital were included.
RESULTS The MESIAH score showed a better discrimination ability, with a C-statistic of 0.835 [95% confidence interval (CI), 0.810-0.861] in the group of treated patients compared to the Barcelona Clinic Liver Cancer (BCLC) staging system [0.739 (95% CI, 0.709-0.769)] before propensity score matching. However, the MESIAH score failed to stratify patients according to their risk of death in the group of untreated patients unlike the BCLC staging system. Propensity score matching analysis confirmed that the MESIAH score was most strongly influenced by whether treatment was given or not.
CONCLUSIONS Although the MESIAH score provided better prognostic stratification than other staging systems in treated HCC patients, it was not helpful in predicting the natural course of HCC. Since the treatment affects patient outcome and prognosis, it is necessary to develop a new staging system that can also reflect the natural course of HCC.
PubMed IF 4.9 소화기내과
23992017

제1저자 이상언 · 교신저자 이해영

, , , , , , , , , , , , , , , , ,
Reverse J-Curve Relationship Between On-Treatment Blood Pressure and Mortality in Patients With Heart Failure.
JACC Heart Fail. 2017;5(11):810-819.

Abstract
OBJECTIVES This study aimed to assess the relationship between on-treatment blood pressure (BP) and clinical outcomes of patients with heart failure (HF).
BACKGROUND Lower BP has been reported to be related to increased mortality in various cardiovascular diseases. The optimal BP level for patients already experiencing HF is contentious.
METHODS The Korean Acute Heart Failure registry prospectively enrolled a total of 5,625 consecutive patients hospitalized for acute HF in 10 tertiary university hospitals in Korea between March 2011 and February 2014. Clinical profiles including BP were collected at admission, discharge, and during outpatient follow-up. Mean on-treatment BP was calculated from BP at discharge and at each follow-up visit. We evaluated the effects of mean on-treatment BP on the clinical outcomes of patients.
RESULTS Patients were followed up for a median 2.2 years. One-year mortality after discharge was 18.2%. The relationship between on-treatment BP and all-cause mortality followed a reversed J-curve relationship. A nonlinear, multivariable Cox proportional hazard model identified a nadir of systolic and diastolic BPs of 132.4/74.2 mm Hg in patients, for whom the mortality rate was lowest (p < 0.0001). The relationship with increased mortality above and below the reference BP was more definitive for diastolic BP and for HF with a preserved ejection fraction.
CONCLUSIONS Systolic and diastolic BPs <130/70 mm Hg at discharge and during follow-up was associated with worse survival in HF patients. These data suggest that the lowest BP possible might not be an optimal target for HF patients. Further studies should establish a proper BP goal in HF patients. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843).
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