SCI 발표논문

2018년 245편

2452018

제1저자 이경희 · 교신저자 유철규

, , , ,
Proteasome Inhibitor-Induced IκB/NF-κB Activation is Mediated by Nrf2-Dependent Light Chain 3B Induction in Lung Cancer Cells.
Mol Cells. 2018;41(12):1008-1015.

Abstract
IκB, a cytoplasmic inhibitor of nuclear factor-κB (NF-κB), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces IκBα degradation via an alternative pathway, lysosome, which results in NF-κB activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced IκBα degradation is necessary. Here, we demonstrated that PI upregulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for IκBα degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced IκBα degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent IκBα degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the IκB/NF-κB pathway, which attenuates the anti-tumor efficacy of PIs.
PubMed IF 8.2 호흡기내과
2442018

제1저자 이의재 · 교신저자 최의근

, , , , , , , , ,
Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study.
PLoS One. 2018;13(12):e0209687.

Abstract
BACKGROUND Patients with atrial fibrillation are known to have a high risk of mortality. There is a paucity of population-based studies about the impact of atrial fibrillation on the mortality risk stratified by age, sex, and detailed causes of death.
METHODS A total of 15,411 patients with atrial fibrillation from the Korean National Health Insurance Service-National Sample Cohort were enrolled, and causes of death were identified according to codes of the 10th revision of the International Classification of Diseases.
RESULTS From 2002 to 2013, a total of 4,479 (29%) deaths were confirmed, and the crude mortality rate for all-cause death was 63.3 per 1,000 patient-years. Patients with atrial fibrillation had a 3.7-fold increased risk of all-cause death compared with the general population. The standardized mortality ratio for all-cause death was the highest in young patients and decreased with increasing age (standardized mortality ratio 21.93, 95% confidence interval 7.60-26.26 in patients aged <20 years; standardized mortality ratio 2.77, 95% confidence interval 2.63-2.91 in patients aged ≥80 years). Women with atrial fibrillation exhibited a greater excess mortality risk than men (standardized mortality ratio 3.81, 95% confidence interval 3.65-3.98 in women; standardized mortality ratio 3.35, 95% confidence interval 3.21-3.48 in men). Cardiovascular disease was the leading cause of death (38.5%), and cerebral infarction was the most common specific disease. Patients with atrial fibrillation had an about 5 times increased risk of death due to cardiovascular disease compared with the general population.
CONCLUSIONS Patients with atrial fibrillation had a 4 times increased risk of mortality compared with the general population. However, the impact of atrial fibrillation on mortality decreased with age and in men. Cerebral infarction was the most common cause of death, and more attention should be paid to reducing the risk of stroke.
PubMed IF 2.8 순환기내과
2432018

제1저자 이태민 · 교신저자 박경우

, , , , , , , ,
Dual Antiplatelet Therapy Duration Determines Outcome After 2- But Not 1-Stent Strategy in Left Main Bifurcation Percutaneous Coronary Intervention.
JACC Cardiovasc Interv. 2018;11(24):2453-2463.

Abstract
OBJECTIVES The aim of this study was to investigate clinical outcomes after left main coronary artery (LM) bifurcation percutaneous coronary intervention (PCI) and the impact of the duration of dual antiplatelet therapy (DAPT) according to treatment strategy.
BACKGROUND There are limited data regarding the optimal PCI strategy for LM bifurcation lesions with new-generation drug-eluting stents.
METHODS A patient-level pooled analysis of 5 nationwide multicenter registries was performed. Rates of target lesion failure, thrombotic adverse cardiovascular events, and their individual components at 3-year were analyzed. Subgroup analysis according to DAPT duration was performed.
RESULTS From 13,172 patients undergoing PCI with new-generation drug-eluting stents, a total of 700 patients were treated for LM bifurcation lesions, 567 with a 1-stent strategy and 133 with a 2-stent strategy. Rates of target lesion failure and target lesion revascularization were higher in the 2-stent group, driven mainly by complex lesion profiles. Risks for thrombotic adverse cardiovascular events and its components were comparable between the 2 strategies. Subgroup analysis showed that risks for target lesion failure and thrombotic adverse cardiovascular events in the 2-stent group were significantly higher than in the 1-stent group in those with DAPT interruption <1 year, while they were similar in those receiving DAPT maintenance ≥1 year.
CONCLUSIONS Up to 20% of patients who underwent LM bifurcation PCI eventually required a 2-stent strategy, which was as safe as a 1-stent strategy with the use of new-generation drug-eluting stents. Careful pre-emptive case selection as well as prolonged DAPT may be necessary when considering a 2-stent strategy in LM PCI given its higher rate of repeat revascularization and lesion failure than the 1-stent approach.
PubMed IF 12.7 순환기내과
2422018

제1저자 조유리,박연수 · 교신저자 김원,이헌주,김동준

, , , , ,
Efficacy of granulocyte colony stimulating factor in patients with severe alcoholic hepatitis with partial or null response to steroid (GRACIAH trial): study protocol for a randomized controlled trial.
Trials. 2018;19(1):696.

Abstract
BACKGROUND Alcoholic hepatitis (AH) has the most severe presentation among alcohol-related liver diseases. Corticosteroids are the most widely recommended treatment for severe AH. However, more innovative, refined treatment measures are required because of its high mortality despite corticosteroid treatment. This study aims to determine whether granulocyte colony stimulating factor (G-CSF) treatment increases short-term survival in patients with severe AH refractory to corticosteroid treatment.
METHODS/DESIGN Patients with severe AH whose Maddrey's discriminant function (MDF) score is ≥ 32 and who will be treated with prednisolone (40 mg/day) for 1 week will be screened. Among them, 190 subjects with a partial response (PR) (Lille score 0.16-0.56), and 78 subjects with a null response (NR) (Lille score ≥ 0.56) will be enrolled. Subjects with PR will be randomized to steroid plus placebo or steroid plus 12 G-CSF injections (5 μg/kg/day for 5 days followed by every 3 days) at a ratio of 1:1. Subjects with a NR will be randomized to the placebo or G-CSF group (1:1). Study subjects in the PR group will be treated with prednisolone for 28 days followed by dose tapering for an additional 2 weeks. The primary endpoint is the 2-month survival rate in the NR group and the 6-month survival rate in the PR group. Child-Turcotte-Pugh, model for end-stage liver disease score, and the change in the proportion of peripheral circulating CD34-positive cells will be analyzed as risk factors for mortality. Preliminary safety data for the initial 10 study subjects enrolled in the PR study will be assessed to determine whether the PR study would be continued, according to the G-CSF-mobilized, peripheral-blood stem cell donor assessment protocol of the National Marrow Donor Program.
DISCUSSION We hypothesized that G-CSF would prolong short-term survival of patients with severe AH refractory to corticosteroid treatment. This is a proof-of-concept trial designed to assess the efficacy of Lille-score-guided G-CSF treatment. This trial is also designed to identify a special subgroup in whom G-CSF rescue treatment would improve liver function and prolong survival.
TRIAL REGISTRATION ClinicalTrials.gov, NCT02442180 . Prospectively registered on 13 May 2015.
PubMed IF 2.1 소화기내과
2412018

제1저자 김재환 · 교신저자 김용태

, , , , , , , ,
Human equilibrative nucleoside transporter 1 (hENT1) expression as a predictive biomarker for gemcitabine chemotherapy in biliary tract cancer.
PLoS One. 2018;13(12):e0209104.

Abstract
Gemcitabine is a principal chemotherapeutic agent for biliary tract cancer (BTC). Expression of human equilibrative nucleoside transporter 1 (hENT1) is regarded as a potential predictive biomarker for a gemcitabine response in some cancers. This study was conducted to investigate the association between hENT1 expression and the effects of gemcitabine on BTC cell lines and on patients with advanced BTC receiving gemcitabine-based chemotherapy. A total of four BTC cell lines, HuCCT1, SNU-478, SNU-1079, and SNU-1196, were tested. mRNA and protein expression levels of hENT1 were measured by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability after gemcitabine treatment was measured in a chemosensitivity assay. For clinical assessment, 40 patients with unresectable or recurrent BTC who were treated with gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) between June 2012 and May 2014 were enrolled. Among the four cell lines, SNU1196 showed the highest mRNA and protein levels of hENT1. Expression of hENT1 showed a linear correlation with the log value of the half-maximal inhibitory concentration of gemcitabine. During incubation with gemcitabine, pretreatment with hENT1-specific small interfering RNA (siRNA) resulted in higher cell viability than that in samples pretreated with control siRNA. In a clinical evaluation, the median progression-free survival was 24 and 11 weeks among patients with strong and weak intratumoral hENT1 immunohistochemical staining (P = 0.05), and the median overall survival was 52 and 26 weeks (P = 0.15), respectively. In conclusion, this study showed that increased hENT1 expression is associated with a stronger toxic effect of gemcitabine on BTC cell lines. The clinical outcomes in this study suggest that increased intratumoral hENT1 immunohistochemical staining is a possible biomarker predicting better therapeutic effects of gemcitabine on patients with advanced BTC. Further studies are needed to determine the precise role of hENT1 in BTC.
PubMed IF 2.8
2402018

제1저자 정성원 · 교신저자 김윤준

, , , , , , ,
Is Combination Antiviral Therapy Mandatory for Maintenance Therapy in Fully Suppressed Multidrug-Resistant Hepatitis B Patients?
Gastroenterol Res Pract. 2018;2018:6948235.

Abstract
AIM The efficacy of tenofovir disoproxil fumarate (TDF) monotherapy as maintenance therapy in multidrug-resistant (MDR) hepatitis B virus (HBV) patients after complete virologic suppression (CVS) has not been well evaluated. We evaluated the efficacy of maintenance TDF monotherapy compared with conventional TDF plus entecavir combination therapy after CVS of MDR HBV.
METHODS In this single-center retrospective study, patients with MDR HBV who were previously treated with entecavir plus TDF combination therapy and achieved CVS were included. Patients were either maintained on entecavir plus TDF combination therapy or switched to TDF monotherapy after CVS. The primary endpoint was the virologic breakthrough, and secondary outcomes were liver cirrhosis (LC) or hepatocellular carcinoma (HCC) development. To overcome immortal time bias, time-varying Cox proportional hazard regression analysis was performed.
RESULTS A total of 201 patients were included, and 153 patients were maintained on entecavir plus TDF combination therapy (combination group); 48 patients were converted from combination therapy to TDF monotherapy (single group) after CVS. Five patients experienced a virologic breakthrough, one patient in the single group owing to poor transient compliance and four patients in the combination group (P = 0.51). One new case of LC developed in the single group; five cases of LC developed in the combination group (P = 0.35). No new HCC development occurred in the single group, while seven cases of HCC developments were noted in the combination group. However, these results were not statistically significant (P = 0.54).
CONCLUSIONS For patients with suppressed HBV DNA, the efficacy of TDF monotherapy as maintenance therapy is comparable to that of entecavir plus TDF combination therapy.
PubMed IF 1.6 소화기내과
2392018

제1저자 정문재,강화평 · 교신저자 이상협,방승민

, , , , , , , , , ,
Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer.
World J Gastrointest Oncol. 2018;10(12):505-515.

Abstract
AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine (GEM)-refractory unresectable pancreatic cancer (PC).
METHODS This study was a prospective, multicenter, one-arm, open-label, phase II trial. Patients with unresectable PC, who showed disease progression during GEM-based chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin (RIO; irinotecan 120 mg/m² and oxaliplatin 60 mg/m²), which was set according to the phase I study of FOLFIRINOX. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events were evaluated. Additionally, changes in quality of life (QoL) were assessed using a questionnaire on QoL.
RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval (CI): 3.7-7.9] and median OS was 9.0 mo (95%CI: 6.4-11.6). Neutropenia (64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia (16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment (45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).
CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.
PubMed IF 2.7 소화기내과
2382018

제1저자 최유정 · 교신저자 최의근

, , , , , , , , , ,
Temporal trends of the prevalence and incidence of atrial fibrillation and stroke among Asian patients with hypertrophic cardiomyopathy: A nationwide population-based study.
Int J Cardiol. 2018;273:130-135.

Abstract
BACKGROUND Atrial fibrillation (AF) and stroke are common in hypertrophic cardiomyopathy (HCM). We aimed to determine the prevalence and incidence of AF and stroke in patients with HCM during a 10-year period.
METHODS Using the Korean National Health Insurance Services database, we identified patients diagnosed with HCM from the entire Korean population between 2005 and 2015. The annual prevalence and incidence of AF and stroke in HCM patients were estimated.
RESULTS The prevalence of AF in HCM patients has gradually increased to 1.6-fold from 13.4% in 2005 to 20.9% in 2015. The incidence of AF ranged from 4.1 to 5.5%, a similar trend was observed for each year in HCM patients. The prevalence of stroke in HCM patients was approximately 10%, while that in HCM patients with AF was about 20%. During 8741 person-years, AF-related stroke occurred in 257 subjects among 2309 HCM patients with new-onset AF. The overall incidence rate of AF-associated stroke was 2.94 per 100 person-years. In subgroup analysis, the incidence rate of AF-associated stroke was 1.49 per 100 person-years in the under 45 year-old group and 1.48 per 100 person-years in the group with CHA₂DS₂-VASc score of 0 or 1 point in HCM patients.
CONCLUSIONS The prevalence of AF in HCM patients gradually increased over 10 years. The annual risk of AF-associated stroke in HCM was over 1% even in younger patients and those with CHA₂DS₂-VASc score of 0 or 1 point, which provide evidence to support the prevention of stroke in HCM patients with AF.
PubMed IF 3.3 순환기내과
2372018

제1저자 오세일 · 교신저자 김영훈

, , , , , , , , , , , , , , , , , , , , , , ,
Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.
J Korean Med Sci. 2018;33(49):e323.

Abstract
BACKGROUND Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction.
METHODS We conducted a multicenter, prospective, non-interventional study. Patients with CHADS₂ ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up.
RESULTS A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS₂ ≥ 2 and 83.6% had CHA₂DS₂-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain.
CONCLUSION INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.
PubMed IF 3.2 순환기내과
2362018

제1저자 유미연,유병철 · 교신저자 이하정

, , , , , , , , , , ,
Trend, not severity, of acute kidney injury affects graft outcome in deceased donor kidney transplantation.
Clin Transplant. 2018;32(12):e13431.

Abstract
Deceased donor kidneys (DDKs) with acute kidney injury (AKI) are difficult to allocate for fear of the expected graft outcome. We aimed to evaluate the impact of donors' AKI severity and trend on graft outcomes in DDK transplantation. This was a retrospective study of DDK transplantation performed from 2005 to 2014. Based on maximum and terminal serum creatinine values before transplantation, the AKI trends were categorized as improving or worsening. Of 413 DDKs, 275 developed AKI: 177 stage 1, 52 stage 2, and 46 stage 3. DDKs with AKI had 212 improving AKI and 63 worsening AKI. Graft outcomes were similar based on AKI stage. Worsening AKI did not affect delayed graft function development; however, it significantly elevated graft failure risk even after adjusting for AKI stage and Kidney Donor Risk Index. Graft survival of the improving group was similar to DDKs with no AKI. This study showed that AKI severity of DDKs did not affect overall graft outcomes. Notably, DDKs with improving AKI showed a similar graft survival rate to DDKs without AKI, although worsening AKI had a worse prognosis. Consideration of the AKI trend, rather than its severity, is needed when DDKs with AKI are allocated.
PubMed IF 1.8 신장내과
2352018

제1저자 황보율 · 교신저자 박영주,조남한

, , , , , , , , , , , , ,
Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer.
J Clin Endocrinol Metab. 2018;103(12):4384-4394.

Abstract
CONTEXT Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.
OBJECTIVE To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
DESIGN AND SETTING We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
RESULTS The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
CONCLUSIONS To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.
PubMed IF 5.4 내분비대사내과
2342018

제1저자 공성혜 · 교신저자 박영주,임청

, , , , , , ,
Subclinical Hypothyroidism and Coronary Revascularization After Coronary Artery Bypass Grafting.
Am J Cardiol. 2018;122(11):1862-1870.

Abstract
We aimed to investigate long-term cardiovascular sequelae after coronary artery bypass grafting (CABG) in patients with subclinical hypothyroidism (SCH). All-cause and cardiovascular-related mortality, and cardiovascular events were retrospectively reviewed in 222 euthyroid and 36 SCH patients who underwent CABG. During a mean follow-up period of 8.2 ± 4.1 years, there were 90 incidents of all-cause deaths, 20 cardiovascular-related deaths, 70 major cardiovascular adverse events, 6 myocardial infarctions, 12 unstable anginas, 31 strokes, 23 hospitalizations due to heart failure, 15 atrial fibrillation (AF) events, and 27 coronary revascularizations. The incidence rate of coronary revascularization was significantly higher in patients with SCH (n = 6, 16.6%) than in euthyroid patients (n = 20, 9.0%), with a hazard ratio (HR) of 3.179 (95% confidence interval [CI] 1.174, 8.605; p = 0.023) after adjustment. In subgroup analysis, SCH patients who experienced postoperative AF within 3 months after CABG surgery had a significantly higher risk of coronary revascularization (n = 4, 25.0%) than euthyroid patients without AF (n = 14, 8.9%) after adjustment (HR 11.759, 95% CI 2.747, 50.343, p = 0.001). The frequency of fatal or nonfatal unstable angina was also higher in patients with SCH (n = 2, 12.5%) than in euthyroid patients (n = 4, 2.5%) (HR 16.999, 95% CI 2.242, 128.860, p = 0.006). In conclusion, preoperative SCH is associated with less favorable cardiovascular outcomes, especially coronary revascularization after CABG. Moreover, SCH patients who develop postoperative AF exhibit significantly increased risks of unstable angina and coronary revascularization. Preoperative evaluation of thyroid function may be helpful for predicting long-term outcomes after CABG.
PubMed IF 2.5 내분비대사내과
2332018

제1저자 김정연 · 교신저자 송영욱

, , , , , , , , , , , ,
Pyruvate Protects against Cellular Senescence through the Control of Mitochondrial and Lysosomal Function in Dermal Fibroblasts.
J Invest Dermatol. 2018;138(12):2522-2530.

Abstract
Mitochondrial dysfunction can drive cellular senescence, which is accompanied by changes in metabolism and increases in senescence-associated secretory phenotypes. Although pyruvate, a key metabolite for numerous aspects of metabolism, has been used as general supplement in synthetic media, the physiological function of pyruvate underlying its protective role against cellular senescence under normal conditions has remained unknown. Here, we show that extracellular pyruvate prevents senescence in normal human dermal fibroblasts through increasing the generation of oxidized nicotinamide adenine dinucleotide (NAD⁺) during the conversion to lactate. Acetylated peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), vacuolar-type H⁺-ATPaseV0A1 (v-ATPaseV0A1), NF-κB p65 subunit (RelA), and histone H3 accumulate under pyruvate deprivation conditions, resulting in the onset of senescence in normal human dermal fibroblasts through the accumulation of abnormal mitochondria generated by lysosomal inactivation-induced mitophagy defects, and through an increase in senescence-associated secretory phenotypes. Furthermore, pyruvate showed a protective effect against aging phenotypes in skin equivalents, which consist of a dermis and epidermis that act similarly to in vivo skin tissues. Our findings reveal a connection between pyruvate and mitochondrial dysfunction in the progression of senescence that is, to our knowledge, previously unreported. These results suggest that the pyruvate deprivation-induced senescence model can be used to study the connection between metabolism and senescence under normal conditions.
PubMed IF 7 류마티스내과
2322018

제1저자 이종찬 · 교신저자 김재환

, , , , , , ,
It is necessary to exam bottom and top slide smears of EUS-FNA for pancreatic cancer.
Hepatobiliary Pancreat Dis Int. 2018;17(6):553-558.

Abstract
BACKGROUND Despite many reports on the diagnostic yield of cytology from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), inter-slide differences are unknown. This prospective study aimed to compare diagnostic yield and cellular characteristics of bottom slides (BS) and top slides (TS) from EUS-FNA cytology performed without an on-site cytopathologist.
METHODS In patients with suspected pancreatic cancer on previous imaging explorations, a single endoscopist performed EUS-FNA and obtained 2 sets of cytology slide (8 BS and 8 TS), 1 cellblock slide, and 1 biopsy slide. Both slide sets were randomly assigned. A cytopathologist with more than 10 years of expertise in pancreatic cytopathology blindly inspected and compared two slide sets.
RESULTS In total, 73 specimens [42 head (57.5%), 16 body (21.9%), and 15 tail (20.5%)] were acquired for final analysis. Seventy-one cases were finally diagnosed with pancreatic cancer. The sensitivity and specificity of BS were 80.3% and 100.0%; and of TS 78.9% and 100.0%, respectively. In analyzing inter-slide difference, 66 cases (90.4%) showed consistent results between BS and TS. However, seven (9.6%) were positive only in one slide sets (4 BS and 3 TS). The proportions of specimens more than moderate and high cellularity were 75.3% and 60.3% in both slide sets (P> 0.99), and the proportion of artifact-free sets were 50.7%, and 52.1% for the BS and TS, respectively (P= 0.869).
CONCLUSIONS Although BS and TS exhibited highly consistent diagnostic yields in cytologic smears from EUS-FNA, the proportion of inter-slide discordance is clinically considerable. Both slide sets need to be examined if there is no on-site cytopathologist.
PubMed IF 3.9 소화기내과
2312018

제1저자 공민규,김학령 · 교신저자 김명아

, , , , , , , , ,
Relationships between blood pressure measurements and target organ damage: Data from the Korea women's chest pain registry.
J Clin Hypertens (Greenwich). 2018;20(12):1724-1730.

Abstract
This study was performed to investigate the association between four BP measurements (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], and pulse pressure [PP]) and four TOD parameters (left ventricular mass index [LVMI], E/e', estimated glomerular filtration rate [eGFR], and obstructive coronary artery disease [CAD]). Data were obtained from a nation-wide registry, composed of 652 patients (471 women, 58.4 ± 10.5 years) with suspected CAD who underwent elective invasive coronary angiography (CAG). A total of 217 patients (33.2%) had obstructive CAD (≥50%). In multivariable analyses, E/e' was associated with SBP, MAP and PP, and CAD was associated with SBP and PP (P < 0.05 for each). All four BP measurements were not associated with LVMI and eGFR (P > 0.05 for each). In patients undergoing elective invasive CAG, SBP, and PP had stronger relationships with E/e' and CAD than DBP and MAP.
PubMed IF 2.9 순환기내과
2302018

제1저자 윤창용 · 교신저자 김나영

, , , , , , , , , ,
Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors.
Helicobacter. 2018;23(6):e12542.

Abstract
BACKGROUND The operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages have been suggested for risk estimation of gastric cancer (GC). However, usefulness of OLGA/OLGIM systems in diffuse type of GC was not investigated so far. The aims of this study were to evaluate the OLGA/OLGIM systems in estimating the GC risk according to Lauren's classification and to investigate the interaction among the risk factors.
MATERIALS AND METHODS The OLGA/OLGIM stages were evaluated in 1398 (765 control and 633 GC patients) who were prospectively enrolled in the Seoul National University Bundang Hospital. Synergistic interaction among the risk factors for GC was calculated using an additive model.
RESULTS Among 387 intestinal-type GC patients, 71 (18.3%) were high-risk OLGA stages (III, IV) and 113 (29.2%) were high-risk OLGIM stages (III, IV). Of the 246 patients with diffuse-type GC, 36 (14.6%) were high-risk OLGA stages and 39 (15.9%) were high-risk OLGIM stages. Multivariable analysis revealed family history of GC, Helicobacter pylori infection, high-risk OLGA stages, and high-risk OLGIM stages as independent risk factors for GC regardless of histologic type (odds ratios [ORs] 1.78, 1.94, 2.63, and 3.18, respectively). There was no significant risk modification among the H. pylori infection, family history of GC, and high-risk OLGA/OLGIM stages.
CONCLUSION High-risk OLGA/OLGIM stages are important prediction markers for GC regardless of H. pylori infection or family history of GC not only for the intestinal type but also for diffuse-type GC.
PubMed IF 4.6 소화기내과
2292018

제1저자 민세희 · 교신저자 정혜승

, , , , , , , , , , ,
Transplantation of human mobilized mononuclear cells improved diabetic neuropathy.
J Endocrinol. 2018;239(3):277-287.

Abstract
Rodent stem cells demonstrated regenerative effects in diabetic neuropathy via improvement in nerve perfusion. As a pre-clinical step, we explored if human mobilized mononuclear cells (hMNC) would have the same effects in rats. hMNC were injected into Rt. hind-limb muscles of streptozotocin-induced diabetic nude rats, and the grafts were monitored using with MRI. After 4 weeks, the effects were compared with those in the vehicle-injected Lt. hind limbs. Nerve conduction, muscle perfusion and gene expression of sciatic nerves were assessed. Induction of diabetes decreased nerve function and expression of Mpz and Met in the sciatic nerves, which are related with myelination. hMNC injection significantly improved the amplitude of compound muscle action potentials along with muscle perfusion and sciatic nerve Mpz expression. On MRI, hypointense signals were observed for 4 weeks at the graft site, but their correlation with the presence of hMNC was detectable for only 1 week. To evaluate paracrine effects of hMNC, IMS32 cells were tested with hepatocyte growth factor (HGF), which had been reported as a myelination-related factor from stem cells. We could observe that HGF enhanced Mpz expression in the IMS32 cells. Because hMNC secreted HGF, IMS32 cells were co-cultured with hMNC, and the expression of Mpz increased along with morphologic maturation. The hMNC-induced Mpz expression was abrogated by treatment of anti-HGF. These results suggest that hMNC could improve diabetic neuropathy, possibly through enhancement of myelination as well as perfusion. According to in vitro studies, HGF was involved in the hMNC-induced myelination activity, at least in part.
PubMed IF 5.7 내분비대사내과
2282018

제1저자 이종찬 · 교신저자 황진혁

, , , , , ,
Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience.
Medicine (Baltimore). 2018;97(50):e13592.

Abstract
Systemic chemotherapy or chemoradiotherapy is the initial primary option for patients with locally advanced pancreatic cancer (LAPC). This study analyzed the effect of FOLFIRINOX and assessed the factors influencing conversion to surgical resectability for LAPC.Sixty-four patients with LAPC who received FOLFIRINOX as initial chemotherapy were enrolled retrospectively. Demographic characteristics, tumor status, interval/dosage/cumulative relative dose intensity (cRDI) of FOLFIRINOX, conversion to resection, and clinical outcomes were reviewed and factors associated with conversion to resectability after FOLFIRINOX were analyzed.After administration of FOLFIRINOX (median 9 cycles, 70% of cRDI), the median patient overall survival (OS) was 17.0 months. Fifteen of 64 patients underwent surgery and R0 resection was achieved in 11 patients. During a median follow-up time of 9.4 months after resection, cumulative recurrence rate was 28.5% at 18 months after resection. The estimated median OS was significantly longer for the resected group (>40 months vs 13 months). There were no statistical differences between the resected and non-resected groups in terms of baseline characteristics, tumor status and hematologic adverse effects. The patients who received standard dose of FOLFIRINOX had higher probability of subsequent resection compared with patients who received reduced dose, although cRDIs did not differ between groups.FOLFIRINOX is an active regimen in patients with LAPC, given acceptable resection rates and promising R0 resection rates. Additionally, our data demonstrate it is advantageous for obtaining resectability to administer FOLFIRINOX without dose reduction.
PubMed IF 2 소화기내과
2272018

제1저자 유정주,장영 · 교신저자 조은주

, , , , , , , , , ,
Timing of upper gastrointestinal endoscopy does not influence short-term outcomes in patients with acute variceal bleeding.
World J Gastroenterol. 2018;24(44):5025-5033.

Abstract
AIM To examine the association between the timing of endoscopy and the short-term outcomes of acute variceal bleeding in cirrhotic patients.
METHODS This retrospective study included 274 consecutive patients admitted with acute esophageal variceal bleeding of two tertiary hospitals in Korea. We adjusted confounding factors using the Cox proportional hazards model and the inverse probability weighting (IPW) method. The primary outcome was the mortality of patients within 6 wk.
RESULTS A total of 173 patients received urgent endoscopy (i.e., ≤ 12 h after admission), and 101 patients received non-urgent endoscopy (> 12 h after admission). The 6-wk mortality rate was 22.5% in the urgent endoscopy group and 29.7% in the non-urgent endoscopy group, and there was no significant difference between the two groups before (P = 0.266) and after IPW (P = 0.639). The length of hospital stay was statistically different between the urgent group and non-urgent group (P = 0.033); however, there was no significant difference in the in-hospital mortality rate between the two groups (8.1% vs 7.9%, P = 0.960). In multivariate analyses, timing of endoscopy was not associated with 6-wk mortality (hazard ratio, 1.297; 95% confidence interval, 0.806-2.089; P = 0.284).
CONCLUSION In cirrhotic patients with acute variceal bleeding, the timing of endoscopy may be independent of short-term mortality.
PubMed IF 7.7 소화기내과
2262018

제1저자 최윤진 · 교신저자 이동호

, , , , , , ,
Optimal Starting Age for Colorectal Cancer Screening in an Era of Increased Metabolic Unhealthiness: A Nationwide Korean Cross-Sectional Study.
Gut Liver. 2018;12(6):655-663.

Abstract
BACKGROUND/AIMS The association between metabolic syndrome and colorectal cancer (CRC) has been suggested as one of causes for the increasing incidence of CRC, particularly in younger age groups. The present study examined whether the current age threshold (50 years) for CRC screening in Korea requires modification when considering increased metabolic syndrome.
METHODS We analyzed data from the National Health Insurance Corporation database, which covers ~97% of the population in Korea. CRC risk was evaluated with stratification based on age and the presence/absence of relevant metabolic syndrome components (diabetes, dyslipidemia, and hypertension).
RESULTS A total of 51,612,316 subjects enrolled during 2014 to 2015 were analyzed. Among them, 19.3% had diabetes, hypertension, dyslipidemia, or some combination thereof. This population had a higher incidence of CRC than did those without these conditions, and this was more prominent in subjects ＜40 years of age. The optimal cutoff age for detecting CRC, based on the highest Youden index, was 45 years among individuals without diabetes, dyslipidemia, and hypertension. Individuals with at least one of these components of metabolic syndrome had the highest Youden index at 62 years old, but the value was only 0.2. Resetting the cutoff age from 50 years to 45 years achieved a 6% increase in sensitivity for CRC detection among the total population.
CONCLUSIONS Starting CRC screening earlier, namely, at 45 rather than at 50 years of age, may improve secondary prevention of CRC in Korea.
PubMed IF 4.1 소화기내과
2252018

제1저자 유민수 · 교신저자 류지곤

, , , , , , ,
Efficacy of Nab-Paclitaxel Plus Gemcitabine and Prognostic Value of Peripheral Neuropathy in Patients with Metastatic Pancreatic Cancer.
Gut Liver. 2018;12(6):728-735.

Abstract
BACKGROUND/AIMS The combination of nab-paclitaxel and gemcitabine (nab-P/Gem) is widely used for treating metastatic pancreatic cancer (MPC). We aimed to evaluate the therapeutic outcomes and prognostic role of treatment-related peripheral neuropathy in patients with MPC treated with nab-P/Gem in clinical practice.
METHODS MPC patients treated with nab-P/Gem as the first-line chemotherapy were included. All 88 Korean patients underwent at least two cycles of nab-P/Gem combination chemotherapy (125 and 1,000 mg/m², respectively). Treatment-related adverse events were monitored through periodic follow-ups. Overall survival and progression-free survival were estimated by the Kaplan-Meier method, and the Cox proportional hazards regression linear model was applied to assess prognostic factors. To evaluate the prognostic value of treatment-related peripheral neuropathy, the landmark point analysis was used.
RESULTS Patients underwent a mean of 6.7±4.2 cycles during 6.3±4.4 months. The median overall survival and progression-free survival rates were 14.2 months (95% confidence interval [CI], 11.8 to 20.3 months) and 8.4 months (95% CI, 7.1 to 13.2 months), respectively. The disease control rate was 84.1%; a partial response and stable disease were achieved in 30 (34.1%) and 44 (50.0%) patients, respectively. Treatment-related peripheral neuropathy developed in 52 patients (59.1%), and 13 (14.8%) and 16 (18.2%) patients experienced grades 2 and 3 neuropathy, respectively. In the landmark model, at 6 months, treatment-related peripheral neuropathy did not have a significant correlation with survival (p=0.089).
CONCLUSIONS Nab-P/Gem is a reasonable choice for treating MPC, as it shows a considerable disease control rate while the treatment-related peripheral neuropathy was tolerable. The prognostic role of treatment-related neuropathy was limited.
PubMed IF 4.1 소화기내과
2242018

제1저자 김근우 · 교신저자 김윤준

, , , , , , , ,
Balloon-Occluded Retrograde Transvenous Obliteration versus Transjugular Intrahepatic Portosystemic Shunt for the Management of Gastric Variceal Bleeding.
Gut Liver. 2018;12(6):704-713.

Abstract
BACKGROUND/AIMS Gastric varices (GVs) are a major cause of upper gastrointestinal bleeding in patients with liver cirrhosis. The current treatments of choice are balloon-occluded retrograde transvenous obliteration (BRTO) and the placement of a transjugular intrahepatic portosystemic shunt (TIPS). We aimed to compare the efficacy and outcomes of these two methods for the management of GV bleeding.
METHODS This retrospective study included consecutive patients who received BRTO (n=157) or TIPS (n=19) to control GV bleeding from January 2005 to December 2014 at a single tertiary hospital in Korea. The overall survival (OS), immediate bleeding control rate, rebleeding rate and complication rate were compared between patients in the BRTO and TIPS groups.
RESULTS Patients in the BRTO group showed higher immediate bleeding control rates (p=0.059, odds ratio [OR]=4.72) and lower cumulative rebleeding rates (log-rank p=0.060) than those in the TIPS group, although the difference failed to reach statistical significance. There were no significant differences in the rates of complications, including pleural effusion, aggravation of esophageal varices, portal hypertensive gastropathy, and portosystemic encephalopathy, although the rate of the progression of ascites was significantly higher in the BRTO group (p=0.02, OR=7.93). After adjusting for several confounding factors using a multivariate Cox analysis, the BRTO group had a significantly longer OS (adjusted hazard ratio [aHR]=0.44, p=0.01) and a longer rebleeding-free survival (aHR=0.34, p=0.001) than the TIPS group.
CONCLUSIONS BRTO provides better bleeding control, rebleeding-free survival, and OS than TIPS for patients with GV bleeding.
PubMed IF 4.1 소화기내과
2232018

제1저자 박선아 · 교신저자 김주성

, , , , , , , , ,
Increased end-stage renal disease risk in patients with inflammatory bowel disease: A nationwide population-based study.
World J Gastroenterol. 2018;24(42):4798-4808.

Abstract
AIM To estimate the risk of end-stage renal disease (ESRD) in patients with inflammatory bowel disease (IBD).
METHODS From January 2010 to December 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified, based on both the International Classification of Diseases, 10^th revision (ICD-10) and the rare, intractable disease registration program codes from the National Health Insurance (NHI) database in South Korea. We compared 38812 patients with IBD to age- and sex-matched non-IBD controls with a ratio of 1:3. Patients newly diagnosed with ESRD were identified with the ICD-10 code.
RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79 (0.2%) patients with IBD and 166 (0.1%) controls. The incidence of ESRD in patients with IBD was 0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio (HR) = 3.03; 95% confidence interval (CI): 1.77-5.20; P < 0.001]. The incidences (per 1000 person-years) of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively (adjusted HR = 6.33; 95%CI: 2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups (0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01; 95%CI: 0.90-4.51; P = 0.089).
CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.
PubMed IF 7.7 소화기내과
2222018

제1저자 김민정, 안은영 · 교신저자 박진균

, , , , , , ,
Association between fever pattern and clinical manifestations of adult-onset Still's disease: unbiased analysis using hierarchical clustering.
Clin Exp Rheumatol. 2018;36(6 Suppl 115):74-79.

Abstract
OBJECTIVES To perform unbiased analysis of fever patterns and to investigate their association with clinical manifestations and outcome of patients with adult-onset Still's disease (AOSD).
METHODS AOSD patients who were treated as in-patients from 2004 through 2015 were grouped according to 24-hour body temperature (BT) by hierarchical clustering using a Euclidean distance metric with complete linkage. The clinical and laboratory characteristics of the groups were then examined.
RESULTS Hierarchical clustering partitioned 70 AOSD patients into three distinct groups. Group 1 (n=14) had the highest mean BT (38.1± 0.4°C) and the widest variation in BT (2.7±0.9°C). Group 2 (n=35) had a lower mean BT (37.4±0.3°C) and a smaller variation (2.1±0.7°C). Group 3 (n=21) had the lowest mean BT (36.7±0.3°C) and the smallest variation (1.5±0.6°C). Clinical features and extent of organ involvement did not differ significantly between groups. However, Group 1 had lower platelet counts and higher lactate dehydrogenase, ferritin levels, and prothrombin time than the other groups. In addition, Group 1 exhibited higher risk of having a macrophage activation syndrome (MAS) and tended to require more intense treatment with corticosteroids and immunosuppressant to achieve clinical remission as compared to other groups.
CONCLUSIONS Hierarchical clustering identified three distinct fever patterns in patients with AOSD. Higher BT was associated with wider variations in diurnal temperature, higher risk of developing MAS, more intense treatment, and longer time to clinical remission, suggesting that fever pattern is a prognostic factor for AOSD.
PubMed IF 3.2 류마티스내과
2212018

제1저자 조준연 · 교신저자 박종선

, , , , , , , , , ,
Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.
Lung Cancer. 2018;125:150-156.

Abstract
OBJECTIVES Immune checkpoint inhibitors (ICIs) can cause pneumonitis in lung cancer patients. We aimed to identify the clinical and radiologic characteristics, incidence, and risk factors of ICI-related pneumonitis in patients with non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS Medical records and chest computed tomography scans of NSCLC patients treated with an ICI over a 5-year period at a tertiary hospital were retrospectively analyzed. Clinical characteristics were compared between patients with and without ICI-related pneumonitis to identify risk factors.
RESULTS Data from 167 eligible patients were analyzed. The incidences of all-grade and grade 3-4 pneumonitis were 13.2% and 4.2%, respectively. The presence of preexisting interstitial lung disease [odd ratio (OR), 6.03; 95% confidence interval (CI), 1.19-30.45; P = 0.030] was associated with a higher incidence of ICI-related pneumonitis. The presence of extrathoracic metastasis [OR, 0.34; 95% CI, 0.13-0.92; P = 0.034] was associated with a lower incidence of ICI-related pneumonitis. The dominant radiologic pattern (72.7%) of ICI-related pneumonitis was organizing pneumonia. Half of the patients with pneumonitis completely recovered or improved; however, the mortality rate was 18.2%.
CONCLUSION ICIs should be used with caution when treating lung cancer patients who have underlying chronic lung disease, especially interstitial lung disease.
PubMed IF 5.3 호흡기내과
2202018

제1저자 최정연 · 교신저자 김광일

, , , , ,
Impact of frailty on do-not-resuscitate orders and healthcare transitions among elderly Koreans with pneumonia.
Clin Interv Aging. 2018;13:2237-2245.

Abstract
PURPOSE Pneumonia poses a significant health risk in aging societies. We aimed to elucidate the determinative value of frailty for do-not-resuscitate (DNR) orders in pneumonia patients.
PATIENTS AND METHODS This was a retrospective cohort study conducted at the Seoul National University Bundang Hospital (SNUBH) in Korea. Medical records of 431 pneumonia patients, aged 65 years and older, who were admitted between June 2014 and May 2015 were analyzed. Patients were categorized into DNR and no-DNR groups.
RESULTS Among the 65 patients (15.1% of pneumonia patients) who completed DNR documents, 24 patients were survived, and 21 patients decided imminent to death (<24 hours before death), with all decisions determined by surrogates. The DNR group tended to be older and frail, with higher rates of renal impairment and malnutrition, and had a lower microbiology detection effort than the no-DNR group. The DNR group used a high number of broad-spectrum antibiotics, experienced high levels of in-hospital (63.1% vs 5.7%, P<0.001) and 30-day (64.6% vs 9.6%, P<0.001) mortality rates, and had prolonged hospital stays (median length of hospital stay, 12 vs 9 days, P=0.020). Frailty was independently associated with DNR status even after adjustment for sepsis, septic shock, and the pneumonia severity index (PSI) score. Frailty also significantly influenced healthcare setting transitions after adjustment for sepsis, septic shock, and the PSI.
CONCLUSION We identified the factors associated with DNR orders and their prognoses among elderly Koreans with pneumonia. Frailty was significantly associated with DNR decision and healthcare setting transitions in pneumonia patients.
PubMed IF 4.1 노인병내과
2192018

제1저자 송영신,원재경 · 교신저자 박영주

, , , , , , , , , ,
Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma.
Thyroid. 2018;28(11):1468-1478.

Abstract
BACKGROUND Among subtypes of follicular variant of papillary thyroid carcinoma (FVPTC), encapsulated FVPTC (EFVPTC) shows more indolent behavior than infiltrative FVPTC (IFVPTC). In particular, noninvasive EFVPTC, now designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), tends to have an excellent prognosis. However, it remains unclear whether the molecular pathogenesis or signature of the various forms of FVPTC is different. By massively parallel sequencing analysis, this study comprehensively characterized the transcriptional and mutational landscape of FVPTC and established correlations with phenotypic subtypes.
METHODS This study included 48 FVPTCs: 17 NIFTPs, 13 invasive EFVPTCs (I-EFVPTCs), and 18 IFVPTCs. For comparison, 55 classical papillary thyroid carcinomas (cPTCs) harboring a BRAF^V600E mutation, six follicular adenomas (FAs), and 15 minimally invasive follicular thyroid carcinomas (miFTCs) with RAS mutations were also included.
RESULTS In NIFTP, the BRAF^V600E mutation was not found, but RAS and other alterations were present in 64.7% and 17.6% of cases, respectively. However, in I-EFVPTC and IFVPTC, the proportions of BRAF^V600E mutation (38.5% and 38.9%, respectively) and of RAS mutations (38.5% and 38.9%, respectively) or other alterations (15.4% and 16.7%, respectively) were similar. On a molecular level, RAS-mutated FVPTCs were all RAS-like except for one IFVPTC case. Transcriptomic profiles of NIFTP, I-EFVPTC, and FA/miFTC were comparable, although the profile of RAS-mutated IFVPTC was altered to activate molecular pathways involved in cell adhesion and invasion. Interestingly, 80% of BRAF^V600E-mutated I-EFVPTCs were also classified as RAS-like, whereas all BRAF^V600E-mutated IFVPTCs were BRAF-like and indistinguishable from cPTC. Molecular pathways associated with cell adhesion and invasion were also differentially activated in BRAF^V600E-mutated IFVPTC.
CONCLUSIONS Molecular profiles of NIFTP and I-EFVPTC may be shared with FA/miFTC, while IFVPTC seems to be associated with a similar profile as cPTC. Activation of cell adhesion and invasion pathways may play a key role in the development of invasive phenotypes of FVPTC.
PubMed IF 6.6 내분비대사내과
2182018

제1저자 최윤진 · 교신저자 이동호

, , , ,
Abdominal obesity, glucose intolerance and decreased high-density lipoprotein cholesterol as components of the metabolic syndrome are associated with the development of colorectal cancer.
Eur J Epidemiol. 2018;33(11):1077-1085.

Abstract
Metabolic syndrome (MetS) and its components has been thought to be involved in the development of colorectal cancer (CRC). However, the results is often inconsistent according to gender or anatomical location of tumor. This study aimed to investigate the association between MetS and its components and CRC development by gender and tumor location. We evaluated the data of 22,809,722 Korean individuals of the National semi-compulsive cohort who underwent regular health check-ups between 2009 and 2012. Compared to subjects without MetS components, the hazard ratio for CRC development in patients with MetS was 1.22 (95% Confidence Interval [CI] 1.20-1.24) and this association was more prominent in men than in women (HR 1.41 95% CI 1.37-1.44 vs. HR 1.23 95% CI 1.20-1.27, P for interaction < 0.001). Left-sided colon cancers were more associated with MetS among men compared to women (HR 1.70, 95% CI 1.61-1.80 vs. HR 1.43, 95% CI 1.33-1.54), while right colon cancers showed a stronger association with MetS among women than men (HR 1.63, 95% CI 1.49-1.78 vs. HR 1.34, 95% CI 1.24-1.44) (all P for interaction < 0.001, respectively). Having two MetS components was still associated with CRC development and the association was the highest when two of glucose intolerance, abdominal obesity and low high-density lipoprotein cholesterol (HDL-C) combined. Individuals with glucose intolerance, abdominal obesity or low HDL-C levels, may need to undergo thorough screening for CRC even if they do not meet the diagnostic MetS criteria.
PubMed IF 6.6 소화기내과
2172018

제1저자 이창훈 · 교신저자 곽민선

, , , ,
Nonalcoholic fatty liver disease is associated with decreased lung function.
Liver Int. 2018;38(11):2091-2100.

Abstract
BACKGROUND & AIMS The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross-sectional and longitudinal analysis.
METHODS Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3 years' follow-up were included. In cross-sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching.
RESULTS Of 11 892 eligible participants (mean age, 47.7 years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross-sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1-second (men, 3.52 vs 3.44 L, P < .001; women, 2.62 vs 2.45 L, P < .001) and forced vital capacity (men, 4.33 vs 4.24 L, P < .001; women, 3.11 vs 2.97 L, P < .001) than the control group. In longitudinal analysis, during the mean follow-up period of 6.6 years, there were no significant differences in forced expiratory volume in 1-second or forced vital capacity decline rates between two groups in the propensity score-matched cohorts (n = 4558). However, those with high nonalcoholic fatty liver disease fibrosis score and fibrosis-4 (men, -21.7 vs -27.4 mL/y, P = .001; women, -22.4 vs -27.9 mL/y, P = .016) showed significantly faster decline in forced vital capacity compared to those with low scores.
CONCLUSIONS Nonalcoholic fatty liver disease was associated with decreased lung function at baseline but was not associated with accelerated lung function decline in the propensity score-matched cohort. However, hepatic fibrosis was significantly associated with rapid forced vital capacity decline.
PubMed IF 6.2 소화기내과
2162018

제1저자 이슬기 · 교신저자 김윤준

, , , , , ,
Synergistic effect of ursodeoxycholic acid on the antitumor activity of sorafenib in hepatocellular carcinoma cells via modulation of STAT3 and ERK.
Int J Mol Med. 2018;42(5):2551-2559.

Abstract
Sorafenib has been approved for the treatment of advanced stage hepatocellular carcinoma but has limited efficacy. Ursodeoxycholic acid exerts cytoprotective activities in hepatocytes and is believed to suppress tumorigenesis through cell cycle arrest and induction of apoptosis. The present study examined whether co‑treatment with ursodeoxycholic acid has a synergistic effect on the antitumor activity of sorafenib in hepatocellular carcinoma cells. Notably, co‑treatment with both agents more effectively inhibited cell proliferation than sorafenib or ursodeoxycholic acid alone. Furthermore, co‑treatment inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and activated extracellular signal‑regulated kinase (ERK), a mitogen‑activated protein kinase, accompanied by excessive intracellular reactive oxygen species generation in hepatocellular carcinoma cells. Thus, chemotherapy with sorafenib and ursodeoxycholic combination may be efficacious in hepatocellular carcinoma by inhibiting cell proliferation and inducing apoptosis through reactive oxygen species‑dependent activation of ERK and dephosphorylation of STAT3. The present findings may represent a promising therapeutic strategy for patients with advanced hepatocellular carcinoma.
PubMed IF 8.5 소화기내과

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