SCI 발표논문

2020년 305편

352020

제1저자 곽수헌, 황유철 · 교신저자 김재현, 김상용

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Comparison of the effects of gemigliptin and dapagliflozin on glycaemic variability in type 2 diabetes: A randomized, open-label, active-controlled, 12-week study (STABLE II study).
Diabetes Obes Metab. 2020;22(2):173-181.

Abstract
AIMS The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients.
MATERIALS AND METHODS In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline.
RESULTS Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups.
CONCLUSIONS Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve.
PubMed IF 6.1 내분비대사내과
342020

제1저자 양한모, 김주영, 조현재 · 교신저자 김효수

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NFATc1+CD31+CD45- circulating multipotent stem cells derived from human endocardium and their therapeutic potential.
Biomaterials. 2020;232:119674.

Abstract
Many studies have shown the existence of cardiac stem cells in the myocardium and epicardial progenitor cells in the epicardium. However, the characteristics of stem cells in the endocardium has not been fully elucidated. In this study, we investigated the origin of newly identified cells in the blood and their therapeutic potential. The new population of cells, identified from human peripheral blood, was quite different from previously reported stem cells. These newly identified cells, which we named Circulating Multipotent Stem (CiMS) cells, were multipotent, and therefore differentiated into multiple lineages in vitro and in vivo. In order to determine the origin of these cells, we collected peripheral blood from a group of patients who underwent bone marrow, liver, heart, or kidney transplantation. We identified the endocardium as the origin of these cells because the Short Tandem Repeat profile of CiMS cells from the recipient had changed from the recipient's profile to the donor's profile after heart transplantation. CiMS cells significantly increased after stimuli to the endocardium, such as catheter ablation for arrhythmia or acute myocardial infarction. CiMS cells circulate in human peripheral blood and are easily obtainable, suggesting that these cells could be a promising tool for cell therapy.
PubMed IF 13.6 순환기내과
332020

제1저자 이소령 · 교신저자 최의근

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Oral Anticoagulation in Asian Patients With Atrial Fibrillation and a History of Intracranial Hemorrhage.
Stroke. 2020;51(2):416-423.

Abstract
Background and Purpose- Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods- Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results- Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHA₂DS₂-VASc score 4.0). Compared with warfarin, NOAC was associated with lower risks of ischemic stroke (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]), ICH (HR, 0.66 [95% CI, 0.47-0.92]), and composite outcome (HR, 0.73 [95% CI, 0.60-0.88]). NOAC was associated with lower risks of fatal stroke (HR, 0.54 [95% CI, 0.32-0.89]), death from composite outcome (HR, 0.53 [95% CI, 0.34-0.81]), and all-cause death (HR, 0.83 [95% CI, 0.69-0.99]) than warfarin. NOAC showed nonsignificant trends toward to reduce fatal ICH compared with warfarin (HR, 0.47 [95% CI, 0.20-1.03]). Conclusions- NOAC was associated with a significant lower risk of ICH and ischemic stroke compared with warfarin. NOAC might be a more effective and safer treatment option for Asian patients with nonvalvular AF and a prior history of ICH.
PubMed IF 11.1 순환기내과
322020

제1저자 소호심 · 교신저자 임종필

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Crohn's disease and ulcerative colitis are associated with different lipid profile disorders: a nationwide population-based study.
Aliment Pharmacol Ther. 2020;51(4):446-456.

Abstract
BACKGROUND The relationships between lipid profiles and IBD remain elusive.
AIM To determine the association of IBD with serum lipid profiles.
METHODS A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD.
RESULTS During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD.
CONCLUSIONS Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC.
PubMed IF 6.8 소화기내과
312020

제1저자 서현정 · 교신저자 김남중

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Prevalence of cryptococcal antigenemia in hospitalized patients with liver cirrhosis.
Med Mycol. 2020;58(2):207-210.

Abstract
The benefits of screening for cryptococcal antigenemia and of preemptive antifungal treatment in HIV-infected patients have been proven. Liver cirrhosis is an important risk factor for cryptococcal infections. Cryptococcal infections are rapidly fatal in patients with liver cirrhosis, especially when diagnosis is delayed. However, screening for cryptococcal antigenemia has not been investigated in these patients. The aim of this study was to investigate the prevalence of cryptococcal antigenemia in hospitalized patients with liver cirrhosis. This prospective study was conducted at Seoul National University Hospital from July 2017 to January 2018. We included patients with liver cirrhosis who were admitted regardless of symptoms or signs suggesting cryptococcal infections. The severity of cirrhosis was evaluated from Child-Pugh and model for end-stage liver disease (MELD) scores. Serum cryptococcal antigenemia was determined using a latex agglutination test. A total of 294 patients were included in the analysis, comprising 104 (35.4%), 100 (34.0%), and 90 (30.6%) patients in Child-Pugh classes A, B, and C, respectively. There were 21 cases of spontaneous bacterial peritonitis, and 14 of hepatic encephalopathy, but none of cryptococcal peritonitis or meningitis. In addition, none of the patient specimens tested positive in the serum cryptococcal latex agglutination test (one-sided 97.5% confidence interval, 0% ∼ 1.2%). Liver cirrhosis is a major risk factor for cryptococcal infections, but the prevalence of serum cryptococcal antigen positivity in patients with liver cirrhosis is very low. Therefore, screening for cryptococcal antigenemia and preemptive antifungal treatment in cirrhotic patients might not be beneficial.
PubMed IF 3.5 감염내과
302020

제1저자 심지수, 이현승 · 교신저자 강혜련, 김혜영

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Aggravation of asthmatic inflammation by chlorine exposure via innate lymphoid cells and CD11cintermediate macrophages.
Allergy. 2020;75(2):381-391.

Abstract
BACKGROUND Chlorine is widely used in daily life as disinfectant. However, chronic exposure to chlorine products aggravates allergic T_H 2 inflammation and airway hyperresponsiveness (AHR). Innate lymphoid cells (ILCs) in airways contribute to the inception of asthma in association with virus infection, pollution, and excess of nutrient, but it is not known whether chronic chlorine exposure can activate innate immune cells. The aim of this study was to evaluate the impact of chlorine inhalation on the innate immunity such as ILCs and macrophages in relation with the development of asthma by using murine ovalbumin (OVA) sensitization/challenge model.
METHODS Six-week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low-dose chlorine exposure by inhalation of naturally vaporized gas of 5% sodium hypochlorite solution. AHR, airway inflammatory cells, from BALF and the population of ILCs and macrophages in the lung were evaluated.
RESULTS The mice exposed to chlorine with OVA (Cl + OVA group) showed enhanced AHR and eosinophilic inflammation compared to OVA-treated mice (OVA group). The population of T_H 2 cells, ILC2s, and ILC3s increased in Cl + OVA group compared with OVA group. CD11c^int macrophages also remarkably increased in Cl + OVA group compared with OVA group. The deletion of macrophages by clodronate resulted in reduction of ILC2s and ILC3s population which was restored by adoptive transfer of CD11c^int macrophages.
CONCLUSIONS Chronic chlorine inhalation contributes to the exacerbation of airway inflammation in asthmatic airway by mobilizing pro-inflammatory macrophage into the lung as well as stimulating group 2 and 3 ILCs.
PubMed IF 11.3 알레르기내과
292020

제1저자 이소령, 최유정 · 교신저자 최의근

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Blood Pressure Variability and Incidence of New-Onset Atrial Fibrillation: A Nationwide Population-Based Study.
Hypertension. 2020;75(2):309-315.

Abstract
Blood pressure variability is a well-known risk factor for cardiovascular disease, but its association with atrial fibrillation (AF) is uncertain. We aimed to evaluate the association between visit-to-visit blood pressure variability and incident AF. This population-based cohort study used database from the Health Screening Cohort, which contained a complete set of medical claims and a biannual health checkup information of the Koran population. A total of 8 063 922 individuals who had at least 3 health checkups with blood pressure measurement between 2004 and 2010 were collected after excluding subjects with preexisting AF. Blood pressure variability was defined as variability independence of the mean and was divided into 4 quartiles. During a mean follow-up of 6.8 years, 140 086 subjects were newly diagnosed with AF. The highest blood pressure variability (fourth quartile) was associated with an increased risk of AF (hazard ratio, 95% CI; systolic blood pressure: 1.06, 1.05-1.08; diastolic blood pressure: 1.07, 1.05-1.08) compared with the lowest (first quartile). Among subjects in the fourth quartile in both systolic and diastolic blood pressure variability, the risk of AF was 7.6% higher than those in the first quartile. Moreover, this result was consistent in both patients with or without prevalent hypertension. In subgroup analysis, the impact of high blood pressure variability on AF development was stronger in high-risk subjects, who were older (≥65 years), with diabetes mellitus or chronic kidney disease. Our findings demonstrated that higher blood pressure variability was associated with a modestly increased risk of AF.
PubMed IF 9.8 순환기내과
282020

제1저자 양민석 · 교신저자 강혜련

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Searching for the Culprit Drugs for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis from a Nationwide Claim Database in Korea.
J Allergy Clin Immunol Pract. 2020;8(2):690-695.e2.

Abstract
BACKGROUND Ethnic differences exist in relation to culprit drugs for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We wanted to determine culprit drugs for SJS and TEN in Korean population.
OBJECTIVE To evaluate culprit drugs for SJS and TEN by applying an algorithm for assessment of drug causality for epidermal necrolysis (ALDEN) in a nationwide administrative database.
METHODS We used the claims database, which included claims data for the entire South Korean population. A retrospective cohort study was conducted by collecting subjects who were first diagnosed with SJS and TEN in 2011. All drugs prescribed to the subjects were reviewed and scored according to the ALDEN score. Drugs with an ALDEN score ≥2 were considered culprit drugs.
RESULTS A total of 187 subjects were included in the culprit drug analysis; 33 very probable, 101 probable, and 57 possible culprit drugs were identified for SJS and TEN according to the ALDEN score. The most frequently suspected culprit drug was allopurinol (19 cases), followed by carbamazepine (17 cases), lamotrigine (13 cases), amoxicillin (9 cases), and dorzolamide (9 cases). Most cases (78.8%, 52 of 66) associated with the use of allopurinol, carbamazepine, lamotrigine, dorzolamide, and methazolamide occurred between 13 and 44 days after initiating the drug.
CONCLUSION We applied the ALDEN score to the claims database to identify possible culprit drugs for SJS and TEN in South Korea. This approach could shed light on research and policymaking for drug adverse reactions.
PubMed IF 6.6 알레르기내과
272020

제1저자 이재하, 문미라 · 교신저자 강혜련

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A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.
J Allergy Clin Immunol Pract. 2020;8(2):696-703.

Abstract
BACKGROUND Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization.
OBJECTIVE To investigate the efficacy and safety of a nondilution, 1-bag protocol in comparison with a conventional multi-bag protocol for desensitization of patients with paclitaxel hypersensitivity.
METHODS Patients who underwent paclitaxel desensitization between 2011 and 2018 were analyzed in this retrospective cohort study. The completion rate, time to completion, and occurrence and severity of breakthrough reaction (BTR) between a 1-bag protocol and a multi-bag protocol were compared.
RESULTS A total of 211 desensitization procedures were performed, of which 207 procedures (98.1%) were completed successfully. The administration time was significantly shorter in the 1-bag protocol group compared with the conventional multi-bag protocol group (266.0 ± 149.3 minutes vs 484.2 ± 178.6 minutes, P < .05) without differences in the completion rate (97.6% vs 98.9%, P = .645), the incidence of BTR (16.1% vs 27.6%, P = .778), and the proportion of severe BTR (2.6% vs 5.7%, P = .134).
CONCLUSIONS A nondilution, 1-bag protocol is noninferior to a multi-bag rapid desensitization protocol and can be a safe and effective option for paclitaxel desensitization.
PubMed IF 6.6 알레르기내과
262020

제1저자 이주엽 · 교신저자 김나영

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Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex.
J Neurogastroenterol Motil. 2020;26(1):106-116.

Abstract
BACKGROUND/AIMS Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex.
METHODS From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay.
RESULTS TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001).
CONCLUSIONS Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.
PubMed IF 3.7 소화기내과
252020

제1저자 Mukul Sherekar, 한세원 · 교신저자 Dominic Esposito

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Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer.
J Biol Chem. 2020;295(4):1105-1119.

Abstract
Neurofibromin is a tumor suppressor encoded by the NF1 gene, which is mutated in Rasopathy disease neurofibromatosis type I. Defects in NF1 lead to aberrant signaling through the RAS-mitogen-activated protein kinase pathway due to disruption of the neurofibromin GTPase-activating function on RAS family small GTPases. Very little is known about the function of most of the neurofibromin protein; to date, biochemical and structural data exist only for its GAP domain and a region containing a Sec-PH motif. To better understand the role of this large protein, here we carried out a series of biochemical and biophysical experiments, including size-exclusion chromatography-multiangle light scattering (SEC-MALS), small-angle X-ray and neutron scattering, and analytical ultracentrifugation, indicating that full-length neurofibromin forms a high-affinity dimer. We observed that neurofibromin dimerization also occurs in human cells and likely has biological and clinical implications. Analysis of purified full-length and truncated neurofibromin variants by negative-stain EM revealed the overall architecture of the dimer and predicted the potential interactions that contribute to the dimer interface. We could reconstitute structures resembling high-affinity full-length dimers by mixing N- and C-terminal protein domains in vitro The reconstituted neurofibromin was capable of GTPase activation in vitro, and co-expression of the two domains in human cells effectively recapitulated the activity of full-length neurofibromin. Taken together, these results suggest how neurofibromin dimers might form and be stabilized within the cell.
PubMed IF 4.1 혈액종양내과
242020

제1저자 이현승 · 교신저자 박흥우

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Role of interleukin-23 in the development of nonallergic eosinophilic inflammation in a murine model of asthma.
Exp Mol Med. 2020;52(1):92-104.

Abstract
Nonallergic eosinophilic asthma (NAEA) is a clinically distinct subtype of asthma. Thus far, the pathophysiologic mechanisms underlying NAEA have not been fully elucidated. This study aimed to determine the role of IL-23 in the pathogenesis of NAEA. We developed a murine model of NAEA using recombinant IL-23 (rIL-23) plus a nonspecific airway irritant [polyinosinic-polycytidylic acid (polyI:C) or diesel exhaust particles (DEPs)] and investigated whether IL-23 plays an important role in the development of NAEA. Intranasal administration of rIL-23 (0.1 μg/mouse) plus polyI:C (0.01 μg/mouse) or DEPs (10 μg/mouse) without allergen resulted in methacholine bronchial hyperresponsiveness and eosinophilic airway inflammation in mice, which are characteristic features of NAEA. rIL-23 plus a low dose nonspecific airway irritants induced the release of innate cytokines from airway epithelium, including IL-33, thymic stromal lymphopoietin and IL-1β; these factors activated types 2 and 3 innate lymphoid cells (ILC2s and ILC3s). ILC2s and ILC3s, but not CD4+ T cells (i.e., adaptive immune cells), were important in the development of NAEA. In addition, we observed that IL-23 receptor expressions increased in airway epithelial cells, which suggests the existence of a positive autocrine loop in our murine model of NAEA. To our knowledge, this is the first report in which administration of rIL-23 plus a nonspecific airway irritant (polyI:C or DEPs) without allergen resulted in features of NAEA in mice similar to those found in humans. IL-23 may constitute a therapeutic target for NAEA in humans.
PubMed IF 17.5 알레르기내과
232020

제1저자 이주영 · 교신저자 임종필

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Changes in Direct Healthcare Costs before and after the Diagnosis of Inflammatory Bowel Disease: A Nationwide Population-Based Study.
Gut Liver. 2020;14(1):89-99.

Abstract
Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sex-matched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis.
PubMed IF 4.1 소화기내과
222020

제1저자 강지훈, Chengbin Zheng · 교신저자 박경우

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Complete Revascularization of Multivessel Coronary Artery Disease Does Not Improve Clinical Outcome in ST-Segment Elevation Myocardial Infarction Patients with Reduced Left Ventricular Ejection Fraction.
J Clin Med. 2020;9(1):jcm9010232.

Abstract
The benefit of complete revascularization (CR) in ST-segment elevation myocardial infarction (STEMI) patients with left ventricular (LV) dysfunction is uncertain. A total of 1314 STEMI patients with multivessel coronary artery disease were analyzed. CR was defined angiographically and by a residual Synergy between PCI with Taxus and Cardiac Surgery trial (SYNTAX) score (SS) <8. Patients with a left ventricular ejection fraction (LVEF) <40% were classified as the reduced LVEF group. The major study endpoints were patient-oriented composite outcome (POCO) and cardiac death during three-year follow-up. Overall, patients that received angiographic CR (579 patients, 44.1%) had significantly lower three-year clinical events compared with incomplete revascularization (iCR). CR reduced three-year POCO and cardiac death rates in the preserved LVEF group (POCO: 13.2% vs. 21.9%, p < 0.001, cardiac death: 1.8% vs. 6.5%, p < 0.001, respectively) but not in the reduced LVEF group (POCO: 26.0% vs. 33.1%, p = 0.275, cardiac death: 15.1% vs. 19.0%, p = 0.498, respectively). Multivariate analysis showed that CR significantly reduced three-year POCO (hazard ration (HR) 0.59, 95% confidence interval (CI) 0.43-0.82) and cardiac death (HR 0.34, 95% CI 0.14-0.80), only in the preserved LVEF group. Additionally, the results were corroborated using the SS-based CR definition. In STEMI patients with multivessel disease, CR did not improve clinical outcomes in those with reduced LVEF.
PubMed IF 3.3 순환기내과
212020

제1저자 문인기, 이서영 · 교신저자 김형관

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Trends of the prevalence and incidence of hypertrophic cardiomyopathy in Korea: A nationwide population-based cohort study.
PLoS One. 2020;15(1):e0227012.

Abstract
Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications.
PubMed IF 2.8 순환기내과
202020

제1저자 양예슬, 양보람 · 교신저자 최성희

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Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study.
Lipids Health Dis. 2020;19(1):5.

Abstract
BACKGROUND Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS).
METHODS This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD).
RESULTS Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015).
CONCLUSIONS LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.
PubMed IF 6.9 내분비대사내과
192020

제1저자 이서연 · 교신저자 김효수

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The MicroRNA-92a/Sp1/MyoD Axis Regulates Hypoxic Stimulation of Myogenic Lineage Differentiation in Mouse Embryonic Stem Cells.
Mol Ther. 2020;28(1):142-156.

Abstract
Hypoxic microenvironments exist in developing embryonic tissues and determine stem cell fate. We previously demonstrated that hypoxic priming plays roles in lineage commitment of embryonic stem cells. In the present study, we found that hypoxia-primed embryoid bodies (Hyp-EBs) efficiently differentiate into the myogenic lineage, resulting in the induction of the myogenic marker MyoD, which was not mediated by hypoxia-inducible factor 1α (HIF1α) or HIF2α, but rather by Sp1 induction and binding to the MyoD promoter. Knockdown of Sp1 in Hyp-EBs abrogated hypoxia-induced MyoD expression and myogenic differentiation. Importantly, in the cardiotoxin-muscle injury mice model, Hyp-EB transplantation facilitated muscle regeneration in vivo, whereas transplantation of Sp1-knockdown Hyp-EBs failed to do. Moreover, we compared microRNA (miRNA) expression profiles between EBs under normoxia versus hypoxia and found that hypoxia-mediated Sp1 induction was mediated by the suppression of miRNA-92a, which directly targeted the 3' untranslated region (3' UTR) of Sp1. Further, the inhibitory effect of miRNA-92a on Sp1 in luciferase assay was abolished by a point mutation in specific sequence in the Sp1 3' UTR that is required for the binding of miRNA-92a. Collectively, these results suggest that hypoxic priming enhances EB commitment to the myogenic lineage through miR-92a/Sp1/MyoD regulatory axis, suggesting a new pathway that promotes myogenic-lineage differentiation.
PubMed IF 11.4 순환기내과
182020

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , , , , ,
Intraoperative Arterial Pressure Variability and Postoperative Acute Kidney Injury.
Clin J Am Soc Nephrol. 2020;15(1):35-46.

Abstract
BACKGROUND AND OBJECTIVES High BP variability may cause AKI because of inappropriate kidney perfusion. This study aimed to investigate the association between intraoperative BP variability and postoperative AKI in patients who underwent noncardiac surgery.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a cohort study of adults undergoing noncardiac surgery in hospitals in South Korea. We studied three cohorts using the following recording windows for intraoperative BP: discovery cohort, 1-minute intervals; first validation cohort, 5-minute intervals; and second validation cohort, 2-second intervals. We calculated four variability parameters (SD, coefficient of variation, variation independent of mean, and average real variability) based on the measured mean arterial pressure values. The primary outcomes were postoperative AKI (defined by the Kidney Disease Improving Global Outcomes serum creatinine cutoffs) and critical AKI (consisting of stage 2 or higher AKI and post-AKI death or dialysis within 90 days).
RESULTS In the three cohorts, 45,520, 29,704, and 7435 patients were analyzed, each with 2230 (443 critical), 1552 (444 critical), and 300 (91 critical) postoperative AKI events, respectively. In the discovery cohort, all variability parameters were significantly associated with risk of AKI, even after adjusting for intraoperative hypotension. For example, average real variability was associated with higher risks of postoperative AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.07 to 1.19) and critical AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.02 to 1.26). Associations were evident predominantly among patients who also experienced intraoperative hypotension. In the validation analysis with 5-minute-interval BP records, all four variability parameters were associated with the risk of postoperative AKI or critical AKI. In the validation cohort with 2-second-interval BP records, average real variability was the only significant variability parameter.
CONCLUSIONS Higher intraoperative BP variability is associated with higher risks of postoperative AKI after noncardiac surgery, independent of hypotension and other clinical characteristics.
PubMed IF 7 신장내과
172020

제1저자 장현덕, 이상언, 양지민 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , ,
Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9.
Eur Heart J. 2020;41(2):239-252.

Abstract
AIMS Proprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9. Herein, we investigated the role of CAP1 in PCSK9-mediated lysosomal degradation of LDLR and plasma LDL cholesterol (LDL-C) levels.
METHODS AND RESULTS The direct binding between PCSK9 and CAP1 was confirmed by immunoprecipitation assay, far-western blot, biomolecular fluorescence complementation, and surface plasmon resonance assay. Fine mapping revealed that the CRD of PCSK9 binds with the Src homology 3 binding domain (SH3BD) of CAP1. Two loss-of-function polymorphisms found in human PCSK9 (S668R and G670E in CRD) were attributed to a defective interaction with CAP1. siRNA against CAP1 reduced the PCSK9-mediated degradation of LDLR in vitro. We generated CAP1 knock-out mice and found that the viable heterozygous CAP1 knock-out mice had higher protein levels of LDLR and lower LDL-C levels in the liver and plasma, respectively, than the control mice. Mechanistic analysis revealed that PCSK9-induced endocytosis and lysosomal degradation of LDLR were mediated by caveolin but not by clathrin, and they were dependent on binding between CAP1 and caveolin-1.
CONCLUSION We identified CAP1 as a new binding partner of PCSK9 and a key mediator of caveolae-dependent endocytosis and lysosomal degradation of LDLR.
PubMed IF 45.3 순환기내과
162020

제1저자 김지현, 홍승욱 · 교신저자 김주성

, , , , , ,
Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor-α.
Inflamm Bowel Dis. 2020;26(2):242-253.

Abstract
BACKGROUND Tumor necrosis factor (TNF)-α is a major proinflammatory cytokine that plays a key role in inflammatory bowel disease (IBD). Inactive rhomboid protein 2 (iRhom2) is essential for activating TNF-α-converting enzyme (TACE) in immune cells, which regulates TNF-α release. The aim of the study was to investigate the role of iRhom2 in intestinal inflammation in IBD.
METHODS The expression of iRhom2 and TACE in lipopolysaccharide (LPS)-stimulated COLO 205 and RAW 264.7 cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of iRhom2 and TACE in the colonic tissue of IBD patients and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-treated mice was determined by RT-PCR and immunohistochemistry. To assess the role of iRhom2 in intestinal inflammation, colitis was induced in wild-type and iRhom2-/- mice by the administration of TNBS enema.
RESULTS In LPS-stimulated COLO 205 and RAW 264.7 cells, the mRNA and protein levels of TACE and iRhom2 were upregulated. The expression of TACE and iRhom2 in the colon of the IBD patients and TNBS-treated mice was significantly enhanced. The inflammatory cells that expressed high levels of iRhom2 in the colon were identified as macrophages. Finally, iRhom2 deficiency ameliorated TNBS-induced colitis by inhibiting TNF-α release.
CONCLUSIONS iRhom2 has an important role in intestinal inflammation through TNF-α secretion in immune cells, which suggests that iRhom2 could be a novel therapeutic target for IBD.
PubMed IF 5.5 소화기내과
152020

제1저자 이상은 · 교신저자 이해영

, , , , , , , , , , , , , , , , ,
Coronary artery bypass graft versus percutaneous coronary intervention in acute heart failure.
Heart. 2020;106(1):50-57.

Abstract
OBJECTIVE Myocardial ischaemia is a leading cause of acute heart failure (AHF). However, optimal revascularisation strategies in AHF are unclear. We aimed to compare two revascularisation strategies, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), in patients with AHF.
METHODS Among 5625 consecutive patients enrolled prospectively in the Korean Acute Heart Failure registry from March 2011 to February 2014, 717 patients who received CABG or PCI during the index hospitalisation for AHF were included in this analysis. We compared adverse outcomes (death, rehospitalisation for HF aggravation or cardiovascular causes, ischaemic stroke and a composite outcome of death and rehospitalisation for HF aggravation or cardiovascular causes) with the use of propensity score matching.
RESULTS For the propensity score-matched cohort with 190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147 deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the median follow-up of 4 years. There was also a trend towards lower rates of rehospitalisation due to cardiovascular events or HF aggravation. Subgroup analysis revealed that the adverse outcomes were significantly lower in the CABG group than in PCI group, especially in patients with old age, three-vessel diseases, significant proximal left anterior descending artery disease and those without left main vessel disease or chronic total occlusion.
CONCLUSIONS Compared with PCI, CABG is associated with significant lower all-cause mortality in patients with AHF. Further studies should evaluate proper revascularisation strategies in AHF.
CLINICAL TRIAL REGISTRATION NCT01389843; Results.
PubMed IF 4.4 순환기내과
142020

제1저자 오도연 · 교신저자 방영주

,
HER2-targeted therapies - a role beyond breast cancer.
Nat Rev Clin Oncol. 2020;17(1):33-48.

Abstract
HER2 is an established therapeutic target in a large subset of women with breast cancer; a variety of agents including trastuzumab, pertuzumab, lapatinib, neratinib and trastuzumab emtansine (T-DM1) have been approved for the treatment of HER2-positive breast cancer. HER2 is also overexpressed in subsets of patients with other solid tumours. Notably, the addition of trastuzumab to first-line chemotherapy has improved the overall survival of patients with HER2-positive gastric cancer, and has become the standard-of-care treatment for this group of patients. However, trials involving pertuzumab, lapatinib and T-DM1 have failed to provide significant improvements in the outcomes of patients with HER2-positive gastric cancer. HER2-targeted therapies are also being tested in patients with other solid tumours harbouring HER2 overexpression, and/or amplifications or other mutations of the gene encoding HER2 (ERBB2), including biliary tract, colorectal, non-small-cell lung and bladder cancers. The experience with gastric cancer suggests that the successes observed in HER2-positive breast cancer might not be replicated in these other tumour types, owing to differences in the level of HER2 overexpression and other aspects of disease biology. In this Review, we describe the current role of HER2-targeted therapies beyond breast cancer and also highlight the potential of novel HER2-targeted agents that are currently in clinical development.
PubMed IF 94.6 혈액종양내과
132020

제1저자 이소령 · 교신저자 오세일

, , , ,
Effect of the variability of blood pressure, glucose level, total cholesterol level, and body mass index on the risk of atrial fibrillation in a healthy population.
Heart Rhythm. 2020;17(1):12-19.

Abstract
BACKGROUND The variability of metabolic parameters might have an impact on the pathophysiology of atrial fibrillation (AF).
OBJECTIVE The purpose of this study was to evaluate the effect of the variability of 4 metabolic components including systolic blood pressure (BP), glucose level, total cholesterol (TC) level, and body mass index (BMI) on the risk of AF in the healthy population without hypertension, diabetes, or dyslipidemia.
METHODS We identified 6,819,829 adult subjects without hypertension, diabetes, or dyslipidemia who had ≥3 health checkups provided by the Korean National Health Insurance Corporation between 2005 and 2012. Glucose level, BP, TC level, and BMI were measured at each visit. Variability was defined as variability independent of the mean (VIM), and VIM of each parameter was divided into 4 groups. High variability was defined as having values in the highest quartile of each parameter.
RESULTS During a mean follow-up of 5.3 ± 1.1 years, 31,302 subjects were newly diagnosed with AF (0.86 per 1000 person-years). Subjects with the highest VIM quartile of BP, TC level, and BMI showed an increased risk of AF compared with those with the lowest VIM quartile, whereas glucose level variability had a marginal association. The composite of the high variability of metabolic parameters showed a graded risk of AF. After multivariable adjustment, subjects having 1, 2, 3, and 4 parameters of the highest VIM had an ∼7%, 13%, 20%, and 35% increased risk of AF compared with those without any highest variability of metabolic parameters.
CONCLUSION The variability of metabolic parameters showed a close association with the risk of AF in those without cardiovascular comorbidities.
PubMed IF 7 순환기내과
122020

제1저자 박준빈 · 교신저자 팽진철, 이승표

, , , , , , , , , , , , , , , ,
Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin.
Am J Respir Crit Care Med. 2020;201(1):95-106.

Abstract
Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, ⁶⁸Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and ⁶⁸Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of ⁶⁸Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of ⁶⁸Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of ⁶⁸Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of ⁶⁸Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:⁶⁸Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that ⁶⁸Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.
PubMed IF 21.7 순환기내과
112020

제1저자 조영민 · 교신저자 이문규

, , , , , , , , , , , , , , , , ,
Efficacy and safety of gemigliptin as add-on therapy to insulin, with or without metformin, in patients with type 2 diabetes mellitus (ZEUS II study).
Diabetes Obes Metab. 2020;22(1):123-127.

Abstract
The objective of this study was to evaluate the efficacy and safety of gemigliptin added to a stable dose of insulin alone or of insulin in combination with metformin in patients with type 2 diabetes mellitus. After a two-week run-in period, patients were randomized 2:1 to receive gemigliptin 50 mg or placebo once daily as add-on to background therapy with insulin or insulin plus metformin for 24 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline at Week 24. Baseline characteristics were similar between the gemigliptin (n = 188) and placebo (n = 95) groups in terms of HbA1c (8.1%). At Week 24, the gemigliptin group showed a statistically significant reduction in mean HbA1c from baseline as compared with placebo (between-group mean difference, -0.7% [95% CI, -0.9% to -0.4%]; P-value < 0.0001). The incidence of overall adverse events and the number of hypoglycaemic adverse events were similar between the study groups. Gemigliptin added to insulin alone or to insulin in combination with metformin resulted in superior glycaemic control compared to that in the placebo group and was well tolerated for 24 weeks in patients with type 2 diabetes mellitus, without causing weight gain or increasing the incidence of hypoglycaemia.
PubMed IF 6.1 감염내과
102020

제1저자 임수 · 교신저자 임수

, , ,
Diabetes drugs and stroke risk: Intensive versus conventional glucose-lowering strategies, and implications of recent cardiovascular outcome trials.
Diabetes Obes Metab. 2020;22(1):6-15.

Abstract
People with diabetes mellitus are at higher risk of ischaemic stroke and worse outcomes thereafter. However, whether it is better to prescribe intensive glucose-lowering treatment compared with conventional treatment in people with diabetes to prevent recurrent stroke is debated. It is also crucial to consider whether specific antidiabetic agents are more efficacious and safer than others for prevention of stroke. In this review, we provide an overview of the efficacy of intensive and conventional glucose-lowering treatment in post-stroke management. Our conclusion is that the overall evidence for a beneficial effect of intensive glycaemic control on risk of stroke is limited. We also discuss evidence from recent large clinical trials of thiazolidinediones and new antidiabetic medications, including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter-2 inhibitors. On the basis of the findings of these trials, our conclusion is that pioglitazone and the GLP-1RA class (other than short-acting lixisenatide) are likely to lessen the occurrence of cerebrovascular disease (by mechanisms not dependent on glucose-lowering per se), whereas there is no consistent evidence for other drug classes.
PubMed IF 6.1 내분비대사내과
92020

제1저자 김문숙 · 교신저자 김홍빈

, , , , , , , , , , , ,
Redundant combinations of antianaerobic antimicrobials: impact of pharmacist-based prospective audit and feedback and prescription characteristics.
Eur J Clin Microbiol Infect Dis. 2020;39(1):75-83.

Abstract
This study aimed to evaluate the impact of the intervention targeting the redundant combination of antianaerobic antimicrobials on its incidence and associated antimicrobial consumption. To reveal the characteristics of the combination and the change in the related workload over time was an additional aim of the study. The combinations of metronidazole or clindamycin with antianaerobic antimicrobials were classified into redundant or acceptable, according to the target indications. A pharmacist-based prospective audit and feedback targeting the redundant antianaerobic combination was conducted. Segmented regression analysis was performed to evaluate the impact of the intervention. As a quantitative index of the interventional activity, the change in the number of signed consultation notes was evaluated. After the initiation of the intervention, the median monthly cumulative incidence of the redundant combination decreased from 5.29 (Interquartile range [IQR] 4.94-5.70) to 3.33 (IQR 2.87-3.71) (p < 0.001) per 1000 admissions per month. The consumption of concurrently administered metronidazole and clindamycin decreased from 3.34 (IQR 2.97-4.10) to 1.74 (IQR 1.19-1.93) (p < 0.001) per 1000 patient-days per month. Segmented regression analysis revealed that the monthly cumulative incidence decreased by 28.5% after the initiation of the intervention (change in level - 1.640, p = 0.019) and the monthly consumption decreased by 33.9% (change in level - 1.409, p = 0.009). The number of consultation notes per 1000 admissions per month decreased over time (regression coefficient - 0.004, p < 0.001). The pharmacist-based intervention significantly reduced the incidence and associated antimicrobial consumption of the redundant antianaerobic combination. The overall related workload reduced steadily over time.
PubMed IF 3.2 감염내과
82020

제1저자 변자민 · 교신저자 이정옥

, , , , , , , , ,
The Role of Anthracyclines in Acute Myeloid Leukemia Consolidation.
Anticancer Res. 2020;40(1):357-366.

Abstract
BACKGROUND/AIM This study was carried out to compare the efficacy and toxicity of consolidation with cytarabine only to consolidation with anthracycline combination in patients with acute myeloid leukemia (AML) achieving complete remission (CR).
PATIENTS AND METHODS This was a multicenter, retrospective, longitudinal cohort study set between January 2010 and December 2016.
RESULTS Generally, high-dose cytarabine Ied to better survival compared to anthracycline-containing consolidation therapy, as expected. However, for patients not undergoing hematopoietic stem cell transplantation (HSCT), anthracycline use was not necessarily associated with worse survival, depending on the number of consolidation cycles. Post-remission, pre-HSCT consolidation with high-dose cytarabine did not negatively affect survival compared to previous reports. For those without FMS-like tyrosine kinase 3 (FLT3) mutation, anthracycline use was associated with a worse survival, but for those with mutation, anthracycline use did not negatively affect survival.
CONCLUSION For patients who are ineligible for HSCT, selective use of anthracycline consolidation can be a viable option, while for patients with the intention of HSCT, post-remission high-dose cytarabine is a reasonable option in the absence of available donors.
PubMed IF 1.8 혈액종양내과
72020

제1저자 강지훈 · 교신저자 한정규

, , , , , , , ,
SYNTAX Score and SYNTAX Score II Can Predict the Clinical Outcomes of Patients with Left Main and/or 3-Vessel Disease Undergoing Percutaneous Coronary Intervention in the Contemporary Cobalt-Chromium Everolimus-Eluting Stent Era.
Korean Circ J. 2020;50(1):22-34.

Abstract
BACKGROUND AND OBJECTIVES The impact of SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SS) and SS II in patients who receive percutaneous coronary intervention with second-generation everolimus-eluting stents (EES) has not been fully validated.
METHODS The SS, SS II were calculated in 1,248 patients with left main and/or 3-vessel disease treated with EES. Patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), any revascularization) and target lesion failure (TLF: cardiac death, target-vessel MI, target lesion revascularization) were analyzed.
RESULTS The mean SS was 21.1±9.6. Three-year POCE increased according to the SS group (15.2% vs. 19.9% vs. 27.4% for low (≤22), intermediate (≥23, ≤32), high (≥33) SS groups, p<0.001). By multivariate Cox proportional hazard analysis, SS group was an independent predictor of 3-year POCE (hazard ratio, 1.324; 95% confidence interval, 1.095-1.601; p=0.004). The receiver operating characteristic curves revealed that the SS II was superior to the SS for 3-year POCE prediction (area under the curve [AUC]: 0.611 vs. 0.669 for SS vs. SS II, p=0.019), but not for 3-year TLF (AUC: 0.631 vs. 0.660 for SS vs. SS II, p=0.996). In subgroup analysis, SS II was superior to SS in patients with cardiovascular clinical risk factors, and in those presenting as stable angina.
CONCLUSIONS The usefulness of SS and SS II was still valid in patients with left main and/or 3-vessel disease. SS II was superior to SS for the prediction of patient-oriented outcomes, but not for lesion-oriented outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00698607, ClinicalTrials.gov Identifier: NCT01605721.
PubMed IF 3.4 순환기내과
62020

제1저자 김미화 · 교신저자 오도연

, , , , ,
Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer.
Cancer Res Treat. 2020;52(1):149-166.

Abstract
PURPOSE Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.
MATERIALS AND METHODS We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings.
RESULTS In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
CONCLUSION Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget.
PubMed IF 4.2 혈액종양내과

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