SCI 발표논문

전체 4,588편

29082019

제1저자 김형준 · 교신저자 이춘택

, , , , , , , , , , ,
Clinical Significance of Pleural Attachment and Indentation of Subsolid Nodule Lung Cancer.
Cancer Res Treat. 2019;51(4):1540-1548.

Abstract
PURPOSE Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival.
MATERIALS AND METHODS Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed.
RESULTS Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91).
CONCLUSION Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.
PubMed IF 4.2 호흡기내과
29072019

제1저자 리우준, 홍준식 · 교신저자 윤성수

, , , , , , , , , ,
ERK-dependent IL-6 positive feedback loop mediates resistance against a combined treatment using danusertib and BKM120 in Burkitt lymphoma cell lines.
Leuk Lymphoma. 2019;60(10):2532-2540.

Abstract
This study was conducted to define the synergistic effect of the PI3K inhibitor BKM120 with the pan-Aurora kinase inhibitor danusertib and the potential mechanism of resistance to the combined inhibitor treatment in Burkitt lymphoma cell lines. The combination of danusertib and BKM120 showed a synergistic effect on Namalwa cells but not on BJAB cells. The combined treatment led to ERK hyperactivation and induced IL-6 secretion in BJAB cells but not in Namalwa cells. A blockade of ERK signaling with trametinib suppressed the combination treatment-induced ERK activation, reduced IL-6 mRNA expression, and downregulated IL-6R mRNA expression, resulting in an improvement in the antitumor effect. We stepwise treated Namalwa cells with both inhibitors using on-and-off treatment cycles and found that Namalwa cells gained chemoresistance by activating the ERK/IL-6 feedback loop, suggesting that the ERK-dependent IL-6 positive feedback loop can compensate for AKT inactivation and is closely associated with adaptive resistance and relapse.
PubMed IF 2.1 혈액종양내과
29062019

제1저자 강은정 · 교신저자 오국환

, , , , , , , , ,
Association Between High-Sensitivity Cardiac Troponin T and Echocardiographic Parameters in Chronic Kidney Disease: Results From the KNOW-CKD Cohort Study.
J Am Heart Assoc. 2019;8(18):e013357.

Abstract
Background It is unclear whether high-sensitivity troponin T (hs-TnT) is associated with subclinical cardiac changes in chronic kidney disease (CKD). We evaluated the relationship between hs-TnT and left ventricular structure and function in a CKD population, according to estimated glomerular filtration rate. Methods and Results We analyzed 2017 patients with CKD stages 1 to 5 (predialysis) in the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) cohort. The predictor was hs-TnT level measured at baseline, and the outcomes were left ventricular hypertrophy (LVH) and systolic and diastolic dysfunction shown by echocardiography at baseline and after 4 years. Participants were categorized into quartiles according to hs-TnT levels. The associations between quartiles of hs-TnT and outcomes were assessed using multivariable logistic regression analysis with confounders including demographics, medical history, and laboratory findings. A receiver operating characteristic curve was used to assess the diagnostic power of hs-TnT for the outcomes as a continuous variable. For subgroup analysis, patients were stratified based on an estimated glomerular filtration rate of 60 mL/min per 1.73 m². Elevated hs-TnT was associated with LVH and diastolic dysfunction at baseline in an adjusted model but was not associated with systolic dysfunction. These associations remained significant for both estimated glomerular filtration rate subgroups. Receiver operating characteristic curve analysis showed that hs-TnT as a continuous variable exhibited fair significance for detection of LVH (area under the curve: 0.689) and diastolic dysfunction (area under the curve: 0.744). Multivariable analysis showed that higher hs-TnT levels at baseline were related to development of LVH but not diastolic dysfunction (n=864). Conclusions In CKD patients, hs-TnT is strongly associated with alterations of left ventricular structure and diastolic dysfunction for both estimated glomerular filtration rate strata. Baseline hs-TnT levels are predictive of new LVH on follow-up.
PubMed IF 6 신장내과
29052019

제1저자 김용철, 이정훈 · 교신저자 양승희, 이정표

, , , , , , , , , , , , , , ,
Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis.
Sci Rep. 2019;9(1):13495.

Abstract
Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.
PubMed IF 4.9 신장내과
29042019

제1저자 이소령, 이태민 · 교신저자 오세일, 그레고리 립

, , , , ,
Meta-Analysis of Oral Anticoagulant Monotherapy as an Antithrombotic Strategy in Patients With Stable Coronary Artery Disease and Nonvalvular Atrial Fibrillation.
Am J Cardiol. 2019;124(6):879-885.

Abstract
Guidelines recommend oral anticoagulant (OAC) monotherapy without antiplatelet therapy (APT) in patients with nonvalvular atrial fibrillation (AF) with stable coronary artery disease (CAD) of >1 year after myocardial infarction or percutaneous coronary intervention. More evidences are required for the safety and efficacy of OAC monotherapy compared with OAC plus APT. PubMed, EMBASE, and Cochrane Database of Systematic Reviews were systematically searched up to February 2019. Nonrandomized studies and randomized clinical trials comparing OAC monotherapy with OAC plus single APT (SAPT) for patients with stable CAD and nonvalvular AF. The primary end point was major adverse cardiovascular events (composite of ischemic or thrombotic events) and secondary outcomes included major bleeding, stroke, all-cause death, and net adverse events (composite of ischemic, thrombotic, or bleeding events). From 6 trials, 8,855 patients were included. There was no significant difference in major adverse cardiovascular event in patients with AF treated using OAC plus SAPT compared with those treated with OAC monotherapy (hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.92 to 1.29). OAC plus SAPT was associated with a significantly higher risk of major bleeding compared with OAC monotherapy (HR 1.61; 95% CI 1.38 to 1.87), as well as in terms of net adverse event (HR 1.21; 95% CI 1.02 to 1.43). There were no significant differences in rates of stroke and all-cause death. In conclusion, in this meta-analysis, OAC monotherapy and OAC plus SAPT treatment showed similar effectiveness, but OAC monotherapy was significantly associated with a lower risk of bleeding compared with OAC plus SAPT in patients with nonvalvular AF and stable CAD.
PubMed IF 2.5 순환기내과
29032019

제1저자 최진호 · 교신저자 이상협

, , , , , , , , ,
Step-wise endoscopic approach to palliative bilateral biliary drainage for unresectable advanced malignant hilar obstruction.
Sci Rep. 2019;9(1):13207.

Abstract
The ideal type of stent utilized at index endoscopic retrograde cholangiopancreatography (ERCP) in management of malignant hilar obstruction (MHO) remains unclear. We aimed to determine the ideal stent choice in patients with MHO. In this retrospective study, patients with unresectable MHO were separated into the plastic stent (PS) group and the self-expandable metal stent (SEMS) group. The primary outcome was the risk and rate of rescue percutaneous transhepatic biliary drainage (PTBD). The secondary outcomes were the progression-free survival, the overall survival and the PTBD-free period (days). Thirty-six patients in the PS group and 38 patients in the SEMS group were enrolled. The risk for PTBD was higher in SEMS group (HR = 2.205, 95% C.I. 0.977-4.977, P = 0.057). The rate of PTBD was significantly lower in the PS group. (22.2% vs 50.0%, P = 0.017) There were no differences in overall survival and progression-free survival (410 and 269 in the PS group, 395 and 266 in the SEMS group, P = 0.663 and P = 0.757). The PTBD-free period was significantly longer in the PS group. (836.43 vs 586.40, P = 0.039) Although comparable in clinical efficacy, utilization of PS at index ERCP may reduce patient's discomfort by avoiding PTBD and prolonging PTBD-free period in patients with MHO.
PubMed IF 4.9 소화기내과
29022019

제1저자 이현정, 김학령 · 교신저자 김명아

, , , , , ,
Subclinical alterations in left ventricular structure and function according to obesity and metabolic health status.
PLoS One. 2019;14(9):e0222118.

Abstract
BACKGROUND Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) structure and function in subjects without overt heart disease.
METHODS In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy).
RESULTS LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e' (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group.
CONCLUSIONS Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease.
PubMed IF 2.8 순환기내과
29012019

제1저자 박세훈, 백충희 · 교신저자 이하정

, , , , , , , , , , ,
Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: a retrospective cohort study.
BMC Nephrol. 2019;20(1):354.

Abstract
BACKGROUND Although immunoglobulin A nephropathy (IgAN) is associated with an increased risk of renal allograft failure, evidences for its treatment, including renin-angiotensin-aldosterone system blockade (RAASB) usage, remain limited.
METHODS In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types, albuminuria changes, and risk of 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used.
RESULTS A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft IgAN diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 [1.09-6.98]; P = 0.03).
CONCLUSIONS In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted.
PubMed IF 2.9 신장내과
29002019

제1저자 정미향, 김학령 · 교신저자 김응주

, , , , , , , , ,
Heart failure awareness in the Korean general population: Results from the nationwide survey.
PLoS One. 2019;14(9):e0222264.

Abstract
BACKGROUND For a better heart failure outcome, it is fundamental to improve the awareness of heart failure at the general population level. We conducted this study to identify the current status of awareness of heart failure in the Korean general population.
METHODS This cross-sectional nationwide survey recruited a total of 1,032 participants aged 30 years or older, based on a stratification systematic sampling method. A 23-item questionnaire was surveyed through telephone interviews.
RESULTS Although 80% of the participants had heard of heart failure, 47% exactly defined what heart failure is. A minority of participants correctly recognized the lifetime risk of developing heart failure (21%) as well as the mortality (16%) and readmission risk (18%) of heart failure and the cost burden of heart failure admission (28%). Regarding preferred treatment options, 71% of the participants chose a treatment option that could improve the quality of life. Approximately two-thirds of the participants agreed that current medical treatment could reduce mortality and improve the quality of life. More than half of the participants (59%) thought that heart failure patients should live quietly and reduce all physical activities. Across survey items, we found a lower awareness state in the elderly groups and people at lower income and educational levels.
CONCLUSIONS The current awareness status of heart failure in the Korean general population is still low. Proactive educational efforts should be made to improve public awareness with special attention to individuals with lower disease awareness.
PubMed IF 2.8 순환기내과
28992019

제1저자 장영, 조유리 · 교신저자 이정훈

, , , , , , , , , , , , , , , ,
Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study.
Cancers (Basel). 2019;11(9):cancers11091295.

Abstract
BACKGROUND AND AIMS Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries.
METHODS This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model.
RESULTS The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts.
CONCLUSIONS The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.
PubMed IF 4.8 소화기내과
28982019

제1저자 공성혜, 김정희 · 교신저자 조남한

, , , , ,
Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults.
Calcif Tissue Int. 2019;105(3):285-293.

Abstract
The study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men > 60 years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength < 26 kg for men and < 18 kg for women, whereas degraded bone microarchitecture was defined as a TBS ≤ 1.2. The mean age was 70.2 ± 6.8 years for men and 71.2 ± 6.7 years for women. Participants within higher dehydroepiandrosterone sulfate (DHEAS) and free testosterone (FT) tertiles were likely to be younger, have greater muscle mass, and have stronger hand grip strength. Based on logistic regression models, men within the lowest FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted odds ratio [OR] 2.28; 95% confidence interval [CI] 1.33-3.91). Women within the lowest DHEAS and FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted OR for DHEAS 1.42; 95% CI 1.02-1.99; adjusted OR for FT 1.77, 95% CI 1.26-2.48). Moreover, men within the lowest FT tertile exhibited degraded bone microarchitecture compared to those in the highest tertile (adjusted OR 2.57, 95% CI 1.46-4.51). However, estradiol was not related to muscle strength or bone microarchitecture in both sexes. In conclusion, in aged men, serum FT was closely associated with muscle strength and bone microarchitecture and in postmenopausal women, serum DHEAS and FT were related to muscle strength.
PubMed IF 3.5 내분비대사내과
28972019

제1저자 김동완 · 교신저자 김동완

, , , , , , , , , , , , , , , , , , , ,
Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial.
Lung Cancer. 2019;135:66-72.

Abstract
OBJECTIVES The aim of this phase 1/2 study was to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of olmutinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who had failed ≥ 1 previous line of EGFR-tyrosine kinase inhibitor (TKI) therapy.
MATERIALS AND METHODS Phase 1 consisted of dose-escalation and four dose-expansion parts (1: olmutinib 300 mg once daily; 2A: 800 mg once daily [EGFR T790 M mutation-positive patients]; 2B: 500 mg twice daily [EGFR T790 M mutation-positive]; 3: 800 mg once daily [EGFR T790 M mutation-negative]). In phase 2, EGFR T790 M mutation-positive patients received olmutinib 800 mg once daily. Data from expansion part 2A and phase 2 were integrated (`pooled phase 2'). Each olmutinib cycle was 21 days. Outcomes included: tumor response, treatment-emergent adverse events (TEAEs), pharmacokinetic parameters.
RESULTS Overall, 272 patients received at least one olmutinib dose: dose-escalation (n = 66), expansion parts (n = 165), phase 2 (n = 41). In pooled phase 2, the overall objective response rate, confirmed by independent review, was 55.1% (38/69 evaluable patients; 95% CI, 42.6-67.1). All responses were partial responses; 23 patients had stable disease. Estimated median progression-free survival was 6.9 (95% CI, 5.6-9.7) months; estimated median overall survival was not reached. The most frequent treatment-related AEs were diarrhea (59.2% of patients), pruritus (42.1%), rash (40.8%), and nausea (39.5%).
CONCLUSION Olmutinib showed effective clinical activity with a manageable safety profile, indicating therapeutic potential for T790M-positive NSCLC patients who have failed ≥ 1 previous line of EGFR-TKI therapy.
PubMed IF 5.3 혈액종양내과
28962019

제1저자 이유수 · 교신저자 김태민

, , , , , , ,
Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations.
J Thorac Oncol. 2019;14(9):1556-1566.

Abstract
INTRODUCTION NSCLC with EGFR exon 20 insertion mutations is the third most common type of EGFR-mutant NSCLC and is resistant to EGFR tyrosine kinase inhibitors (TKIs). This study was conducted to evaluate the efficacies of first- to third-generation EGFR TKIs against NSCLC cells harboring EGFR exon 20 insertion mutations.
METHODS We developed seven EGFR exon 20 insertion-mutant Ba/F3 models and one patient-derived NSCLC (SNU-3173) of subtypes A763insFQEA, V769insASV, D770insSVD, D770insNPG, P772insPR, H773insH, H773insNPH, and H773insAH. Cell viability assays, immunoblotting, and N-ethyl-N-nitrosourea mutagenesis screenings were performed. EGFR exon 20 insertion-mutant structures and couplings with osimertinib, a third-generation EGFR TKI, were modeled and compared.
RESULTS EGFR exon 20 insertion-mutant NSCLC cells, excluding EGFR A763insFQEA, were resistant to first-generation EGFR TKIs (concentration that inhibits 50% [IC₅₀], 1.1 ± 0.067 to 5.4 ± 0.115 μM). Mutants were sensitive to second-generation EGFR TKIs (IC₅₀, 0.02 ± 0.0002 to 161.8 ± 18.7nM), except EGFR H773insH (IC₅₀, 46.3 ± 8.0 to 352.5 ± 22.7nM). The IC₅₀ ratios for mutant to wild-type cells were higher than those for third-generation EGFR TKIs. Third-generation EGFR TKI osimertinib was highly potent against EGFR exon 20 insertion-mutant cells (IC₅₀, 14.7-62.7 nM), including EGFR H773insH, and spared wild-type EGFR cells. N-ethyl-N-nitrosourea mutagenesis screening of EGFR exon 20 insertion-mutant Ba/F3 cells showed various second sites for EGFR mutations, mostly at exons 20 and 21, including E762K, P794S, and G796D. In addition, osimertinib-resistant cells were established by stepwise exposure to osimertinib and harbored EGFR E762K mutation.
CONCLUSIONS Osimertinib is active against EGFR exon 20 insertion-mutant NSCLC and flexibly binds within drug-binding pockets in preclinical models.
PubMed IF 23.3 혈액종양내과
28952019

제1저자 김영찬, 이상언, 김솜이, 장현덕 · 교신저자 김효수

, , , , , , , ,
Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation.
Nat Chem Biol. 2019;15(9):907-916.

Abstract
Toll-like receptor (TLR)/myeloid differentiation primary response protein (MYD88) signaling aggravates sepsis by impairing neutrophil migration to infection sites. However, the role of intracellular fatty acids in TLR/MYD88 signaling is unclear. Here, inhibition of fatty acid synthase by C75 improved neutrophil chemotaxis and increased the survival of mice with sepsis in cecal ligation puncture and lipopolysaccharide-induced septic shock models. C75 specifically blocked TLR/MYD88 signaling in neutrophils. Treatment with GSK2194069 that targets a different domain of fatty acid synthase, did not block TLR signaling or MYD88 palmitoylation. De novo fatty acid synthesis and CD36-mediated exogenous fatty acid incorporation contributed to MYD88 palmitoylation. The binding of IRAK4 to the MYD88 intermediate domain and downstream signal activation required MYD88 palmitoylation at cysteine 113. MYD88 was palmitoylated by ZDHHC6, and ZDHHC6 knockdown decreased MYD88 palmitoylation and TLR/MYD88 activation upon lipopolysaccharide stimulus. Thus, intracellular saturated fatty acid-dependent palmitoylation of MYD88 by ZDHHC6 is a therapeutic target of sepsis.
PubMed IF 15.8 순환기내과
28942019

제1저자 김률 · 교신저자 김범석

, , , , , , ,
First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non-small-cell Lung Cancer: A Systematic Review and Network Meta-analysis.
Clin Lung Cancer. 2019;20(5):331-338.e4.

Abstract
BACKGROUND This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non-small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone.
MATERIALS AND METHODS A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy.
RESULTS A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%.
CONCLUSIONS For patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted.
PubMed IF 3.9 혈액종양내과
28932019

제1저자 박지은, 김미화 · 교신저자 오도연

, , , , , , ,
GC1118, a novel anti-EGFR antibody, has potent KRAS mutation-independent antitumor activity compared with cetuximab in gastric cancer.
Gastric Cancer. 2019;22(5):932-940.

Abstract
BACKGROUND EGFR overexpression in gastric cancer (GC) has been reported in about 30% of patients. However, the anti-EGFR antibodies cetuximab and panitumumab have failed to improve overall survival of GC patients in combination with cytotoxic chemotherapy compared with chemotherapy alone. GC1118, a novel anti-EGFR antibody with a distinct binding epitope compared with cetuximab or panitumumab, has not been tested in GC.
METHODS GC cell lines, SNU-1, SNU-5, SNU-16, SNU-216, SNU-484, SNU-601, SNU-620, SNU-638, SNU-668, SNU-719, AGS, MKN-45, NCI-N87, and KATO-III, were employed to test the effect of cetuximab or GC1118 alone, and combined with the cytotoxic agent cisplatin or 5-fluorouracil (5-FU). Cells were also treat with or without high-affinity ligands EGF 20 ng/ml or HB-EGF 100 ng/ml.
RESULTS GC1118 exhibited a more potent growth inhibition effect in the majority of cell lines than cetuximab in MTT assay, regardless of the KRAS mutation status of cell lines. Co-treatment of GC1118 and cisplatin or 5-FU inhibited colony formation and migration to a greater extent, even following EGFR ligand stimulation. Ligand-induced p-AKT and p-ERK upregulation were more potently inhibited by combination treatment with GC1118 and chemotherapeutic agents compared with cetuximab plus chemotherapeutic agents. GC1118 also showed more potent anti-tumor effects compared with cetuximab in a mouse xenograft model.
CONCLUSION Taken together, GC1118 alone or in combination with cytotoxic chemotherapeutic agents exerted more potent anti-tumor effects than cetuximab in GC cells, regardless of KRAS status. These findings support the further clinical development of GC1118 for the treatment of GC.
PubMed IF 6.1 혈액종양내과
28922019

제1저자 변자민 · 교신저자 윤성수

, , , , , , ,
Daratumumab Monotherapy in Heavily Pretreated Asian Patients With Relapsed and Refractory Multiple Myeloma: A Real-world Experience.
Anticancer Res. 2019;39(9):5165-5170.

Abstract
BACKGROUND/AIM Daratumumab is a promising novel agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its efficacy and toxicity profiles in real-world patients, especially in the Asian population.
PATIENTS AND METHODS This was a multicenter, retrospective, longitudinal cohort study set between January 2017 and April 2019. We collected and analyzed clinical and survival data of 21 patients treated with daratumumab monotherapy. All patients were previously exposed to proteasome inhibitors and immunomodulatory drugs.
RESULTS The overall response rate was 42.1%, including one complete remission (4.8%) and three very good partial responses (14.3%). The cycles of daratumumab delivered were three (range=1-10 cycles) and the median progression-free survival was 6 months, while the overall survival was not reached. Infusion reaction was observed in nine patients (42.9%), and one discontinued permanently. Fatigue was the most common adverse event (52.4%), and there were five cases of documented infection during daratumumab treatment, two of them leading to the death of the patient.
CONCLUSION Daratumumab monotherapy showed fairly promising activity with modest tolerance in heavily treated Asian RRMM patients.
PubMed IF 1.8 혈액종양내과
28912019

제1저자 조유리, 임수경 · 교신저자 김원

, , , , , , , , , , , , ,
Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm.
Liver Int. 2019;39(9):1722-1731.

Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy-proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence-based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm.
METHODS This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy-evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high-grade dysplasia or adenocarcinoma.
RESULTS Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy-proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low-grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12-3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01-7.87; P = 0.049).
CONCLUSIONS The presence of biopsy-proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early.
PubMed IF 6.2 소화기내과
28902019

제1저자 정성원 · 교신저자 이정훈

, , , , , , , , , , , , ,
Additional fibrate treatment in UDCA-refractory PBC patients.
Liver Int. 2019;39(9):1776-1785.

Abstract
BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC.
METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method.
RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04).
CONCLUSIONS In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.
PubMed IF 6.2 소화기내과
28892019

제1저자 조준연 · 교신저자 이연주

, , , , , , , , , ,
Factors Associated With Quality of Death in Korean ICUs As Perceived by Medical Staff: A Multicenter Cross-Sectional Survey.
Crit Care Med. 2019;47(9):1208-1215.

Abstract
OBJECTIVES Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the "well-dying" law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death.
DESIGN A multicenter cross-sectional survey study.
SETTING Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals.
PATIENTS Deceased patients from June 2016 to May 2017.
INTERVENTIONS Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient's death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death.
MEASUREMENTS AND MAIN RESULTS A total of 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death.
CONCLUSIONS The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients' families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs.
PubMed IF 7.5 호흡기내과
28882019

제1저자 이지현, 이소령 · 교신저자 최의근

, , , , , , ,
Temporal Trends of Cardiac Implantable Electronic Device Implantations: a Nationwide Population-based Study.
Korean Circ J. 2019;49(9):841-852.

Abstract
BACKGROUND AND OBJECTIVES Implantation of cardiac implantable electronic devices (CIED), including permanent pacemakers (PM), implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices, has increased significantly over the past several years. However, limited data exists regarding temporal trends of CIED implantations in Asian population. This study aimed to investigate temporal trends of CIED treatment in Korea.
METHODS Using the National Health Insurance Service database of the entire Korean adult population, temporal trends of CIED procedures between 2009 and 2016 were evaluated. Additionally, temporal changes in the prevalence of patients' comorbidities were evaluated.
RESULTS A total of 35,421 CIED procedures (new implantations: 27,771, replacements: 7,650) were performed during the study period. The mean age of new CIED recipients and the prevalence of comorbidities, including hypertension, diabetes mellitus, heart failure, stroke, and atrial fibrillation, increased substantially with time. Compared to 2009, the number of new implantations of PM, ICD, and CRT devices increased by 2.0 (1,977 to 3,910), 3.6 (230 to 822), and 4.9 (44 to 217) times in 2016, respectively. The annual new implantation rate of CIED also increased accordingly (5.1 to 9.3 for PM, 0.6 to 1.9 for ICD, and 0.1 to 0.5 for CRT devices, per 100,000 persons).
CONCLUSIONS The number of CIED implantation increased substantially from 2009 to 2016 in Korea. Also, the patients with CIED have been changed to be older and have more comorbidities. Therefore, the burden of health care cost in patients with CIED would be expected to increase in the future.
PubMed IF 3.4 순환기내과
28872019

제1저자 이현정 · 교신저자 김형관

, , , , , , , ,
Novel Oral Anticoagulants for Primary Stroke Prevention in Hypertrophic Cardiomyopathy Patients With Atrial Fibrillation.
Stroke. 2019;50(9):2582-2586.

Abstract
Background and Purpose- Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods- Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results- During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32-0.68), ICH (HR, 0.31; 95% CI, 0.14-0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40-0.96), death (HR, 0.45; 95% CI, 0.31-0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38-0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions- NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.
PubMed IF 11.1 순환기내과
28862019

제1저자 박진균 · 교신저자 이은봉

, , , ,
Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial.
Ann Rheum Dis. 2019;78(9):1283-1284.

PubMed IF 24 류마티스내과
28852019

제1저자 황도연 · 교신저자 구본권

, , , , , , , , , , , ,
Influence of target vessel on prognostic relevance of fractional flow reserve after coronary stenting.
EuroIntervention. 2019;15(5):457-464.

Abstract
AIMS We sought to investigate the influence of the target vessel on the prognostic relevance of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI).
METHODS AND RESULTS A total of 835 patients with available FFR after second-generation drug-eluting stent (DES) implantation were included in this study. The primary outcome was target-vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularisation. The target vessel was the left anterior descending artery (LAD) in 603 patients (72.2%) and non-LAD in 232 patients (27.8%). The distribution pattern of post-PCI FFR values was different between the LAD and non-LAD (p<0.001). The optimal cut-off values of post-PCI FFR for predicting TVF were 0.82 and 0.88 in the LAD and non-LAD, respectively. The cumulative incidence of TVF was significantly higher in patients with lower post-PCI FFR than each cut-off value (10.9% vs. 2.5%, hazard ratio [HR] 4.08, 95% confidence interval [CI]: 2.63-6.34, p<0.001 in LAD; 8.0% vs. 1.9%, HR 6.00, 95% CI: 1.78-20.26, p=0.004 in non-LAD).
CONCLUSIONS Higher post-PCI FFR after second-generation DES implantation was associated with better clinical outcomes. Different cut-off values of post-PCI FFR need to be applied according to the target vessel. ClinicalTrials Identifier: NCT01873560.
PubMed IF 9.2 순환기내과
28842019

제1저자 조재영 · 교신저자 이창훈

, , , , , , , , , ,
Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients.
Respiration. 2019;98(4):312-320.

Abstract
BACKGROUND The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD).
OBJECTIVE The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms.
METHODS We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George's Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed.
RESULTS After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference -4.7 [95% CI -7.9 to -1.6] and -4.8 [95% CI -7.9 to -1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference -5.0 [95% CI -8.6 to -1.4]) compared to no regular treatment at 12 months of follow-up.
CONCLUSIONS Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.
PubMed IF 2.6 호흡기내과
28832019

제1저자 이인준, 이정훈 · 교신저자 정진욱

, , , , , , , , , ,
Effectiveness of drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization for small hepatocellular carcinoma in Child-Pugh class A patients.
Ther Adv Med Oncol. 2019;11:1758835919866072.

Abstract
BACKGROUND This study aimed to compare the therapeutic effectiveness including progression-free survival (PFS), overall survival (OS), and safety of conventional transarterial chemoembolization (cTACE) and drug-eluting bead transarterial chemoembolization (DEB-TACE) in a superselective fashion for the patients with nodular hepatocellular carcinoma (HCC) (n ⩽ 5) and Child-Pugh class A.
METHODS A total of 198 consecutive patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A liver function who were initially treated with cTACE (n = 125) or DEB-TACE (n = 57) were included retrospectively. The primary endpoint was PFS. Secondary endpoints included time-to-target lesion progression (TTTLP), OS, and safety.
RESULTS The median follow up was 62 months (range, 1-87 months). The PFS was significantly longer in the cTACE group than in the DEB-TACE group (median, 18 months versus 7 months; hazard ratio [HR] = 0.658, log-rank p = 0.031), whereas OS was comparable (log-rank p = 0.299). TTTLP was significantly longer in the cTACE group than in the DEB-TACE group (median, 34 months versus 11 months; log-rank p < 0.001). In the stratification analysis based on tumor size, the cTACE group showed significantly longer TTTLP than the DEB-TACE group in the 1.0-2.0 cm and 2.1-3.0 cm subgroups (HR = 0.188, log-rank p < 0.001 and HR = 0.410, p = 0.015, respectively) but not in the 3.1-5.0 cm and 5.1-10.0 cm subgroups (all p > 0.05). Postembolization syndrome occurred more frequently in the cTACE group than in the DEB-TACE group (p = 0.006).
CONCLUSIONS DEB-TACE is followed by significantly shorter PFS than cTACE in patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A, although OS is comparable. Postembolization syndrome occurs more frequently in cTACE than in DEB-TACE.
PubMed IF 4.1 소화기내과
28822019

제1저자 김경진 · 교신저자 손대원

, , ,
Postoperative persistent diastolic dyssynchronous expansion in patients with Ebstein's anomaly.
PLoS One. 2019;14(8):e0220890.

Abstract
In Ebstein's anomaly, maximal expansion in the atrialized right ventricle (RV) occurs during early diastole, whereas that of the functional RV occurs in late diastole, resulting in diastolic dyssynchronous expansion (DSE). We quantitatively assessed DSE and identified preoperative factors correlated with persistent DSE after surgery. Seventeen patients diagnosed with Ebstein's anomaly in whom transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) images available were retrospectively analyzed for quantitative DSE assessment and 10 patients who underwent surgery and postoperative TTE available were additionally analyzed for postoperative DSE. Severity of DSE was assessed by the time difference of maximal expansion between the atrialized and functional RV divided by the cardiac cycle length × 100 ("DSE index"). Relations between DSE and, clinical, electrophysiologic parameters and the severity of tricuspid valve (TV) tethering (the RV length / tethering height during diastole: "Tethering index") were assessed. In total patients, median DSE index and tethering index were 30.3 and 2.1 respectively, and the DSE index was correlated with tethering index (rs = 0.664, P = 0.004). In 10 patients who underwent surgery, this association remained after surgery and at 2-year follow up. Tethering index ≥2.5 separated patients with and without persistent DSE. In conclusion, DSE exists in Ebstein's anomaly. DSE index is related to the tethering index and DSE persists postoperatively if tethering index ≥ 2.5. As the persistent DSE might possibly impede the optimal recovery of RV function after surgery, severity of TV tethering should take into account in considering surgery.
PubMed IF 2.8 순환기내과
28812019

제1저자 임선희 · 교신저자 김나영

, , , , , , , , , , , , , ,
Positive Association Between Helicobacter pylori Infection and Metabolic Syndrome in a Korean Population: A Multicenter Nationwide Study.
Dig Dis Sci. 2019;64(8):2219-2230.

Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection causes extra-gastrointestinal as well as gastric diseases. This analytical cross-sectional study was performed to investigate the association between H. pylori infection and metabolic syndrome in a Korean population.
METHODS Anthropometric and metabolic data, as well as anti-H. pylori IgG antibodies, were measured in 21,106 subjects who participated in a health checkup between January 2016 and June 2017. The classification of metabolic syndrome followed the revised National Cholesterol Education Program criteria.
RESULTS After excluding subjects with a history of H. pylori eradication therapy, or gastric symptoms, the seropositivity of H. pylori was 43.2% in 15,195 subjects. H. pylori-positive participants had significantly higher body mass index (BMI), waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein (HDL-C) than did seronegative participants (P < 0.05). After adjusting for confounders, high TC, low HDL-C, and high LDL-C were associated with H. pylori seropositivity. Finally, the prevalence of metabolic syndrome was higher in H. pylori-seropositive subjects than in negative ones (27.2% vs. 21.0%, P < 0.05), and H. pylori seropositivity increased the likelihood of metabolic syndrome (OR 1.19, 95% CI 1.09-1.31, P < 0.001) after adjusting for sex, age, BMI, smoking, residence, household income, and education level. However, the association between H. pylori seropositivity and metabolic syndrome disappeared in those ≥ 65 years old.
CONCLUSIONS H. pylori infection plays an independent role in the pathogenesis of metabolic syndrome in Koreans under 65 years old.
PubMed IF 2.8 소화기내과
28802019

제1저자 황도연, 강지훈 · 교신저자 양한모

, , , , , , , ,
Better Prognosis After Complete Revascularization Using Contemporary Coronary Stents in Patients With Chronic Kidney Disease.
Circ Cardiovasc Interv. 2019;12(8):e007907.

Abstract
BACKGROUND The prognostic value of angiographic complete revascularization in patients with chronic kidney disease (CKD) has not been thoroughly investigated, especially for contemporary coronary stents. We compared the clinical outcomes of complete and incomplete revascularization with second-generation drug-eluting stent, according to the presence of CKD.
METHODS From the Grand Drug-Eluting Stent Registry (N=17 286) in Korea, we selected 8471 patients, who were treated with second-generation drug-eluting stent and had glomerular filtration rate and quantitative coronary angiography data (3014 [35.6%] patients with CKD and 5457 (64.4%) patients with preserved renal function). Angiographic complete revascularization was defined as a residual SYNTAX score (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) of 0. The primary outcome was the patient-oriented composite outcome at 3 years, including all-cause death, any myocardial infarction, and any revascularization.
RESULTS The patient-oriented composite outcome rate after complete revascularization was significantly lower than that after incomplete revascularization in patients with CKD (14.6% versus 21.8%; adjusted hazard ratio, 0.79; 95% CI, 0.64-0.96; P=0.020) and in patients with preserved renal function (8.0% versus 12.0%; adjusted hazard ratio 0.77; 95% CI, 0.63-0.94; P=0.011). The cutoff values of residual SYNTAX scores for predicting better patient-oriented composite outcomes were different according to the presence of CKD, that is, <3 and <8 in patients with CKD and with preserved renal function, respectively.
CONCLUSIONS Angiographic complete revascularization led to better clinical outcomes in patients with CKD and with preserved renal function. However, the residual SYNTAX score to achieve a better outcome was lower in patients with CKD than with preserved renal function, favoring more aggressive revascularization in patients with CKD.
PubMed IF 7.2 순환기내과
28792019

제1저자 김진원 · 교신저자 오도연

, , , , , , ,
Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: phase Ib study.
Br J Cancer. 2019;121(4):332-339.

Abstract
BACKGROUND A phase Ib study of binimetinib and capecitabine for gemcitabine-pretreated biliary tract cancer (BTC) patients was conducted.
METHODS Binimetinib and capecitabine were dosed twice daily on days 1-14, in 3-week cycles. In the dose-escalation (DE) part, three dose levels (DL) were tested (DL1: binimetinib/capecitabine, 15 mg/1000 mg/m²; DL2: 30 mg/1000 mg/m²; DL3: 30 mg/1250 mg/m²).
RESULTS In the DE part, nine patients were recruited and no dose-limiting toxicity was noted. Therefore, the recommended phase 2 dose was determined as DL3. In the expansion part, 25 patients were enrolled. In total, 34 patients, 25 (73.5%) and 9 patients (26.5%) were second-line and third-line settings, respectively. The 3-month progression-free survival (PFS) rate was 64.0%, and the median PFS and overall survival (OS) were 4.1 and 7.8 months. The objective response rate and disease control rate were 20.6% and 76.5%. In total, 68.4% of stable diseases were durable (> 12 weeks). Furthermore, patients with RAS/RAF/MEK/ERK pathway mutations (38.5%) showed significantly better tumour response (p = 0.028), PFS (5.4 vs. 3.5 months, p = 0.010) and OS (10.8 vs. 5.9 months, p = 0.160) than wild type. Most of the adverse events were grade 1/2 and manageable.
CONCLUSIONS A combination of binimetinib and capecitabine shows acceptable tolerability and promising antitumor efficacy for gemcitabine-pretreated BTC, especially in patients with RAS/RAF/MEK/ERK pathway mutations.
CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (Identifier: NCT02773459).
PubMed IF 7.8 혈액종양내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.