SCI 발표논문

2019년 297편

1472019

제1저자 김우진 · 교신저자 김태민, 박철기

, , , , , , , ,
Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma.
J Neurooncol. 2019;143(2):321-328.

Abstract
PURPOSE Lymphopenia in patients with glioblastoma (GBM) is related to treatment as well as disease progression. This retrospective study investigated the prevalence, influencing factors, recoverability, and clinical significance of lymphopenia in GBM patients treated with concomitant chemoradiotherapy (CCRT).
PATIENTS AND METHODS A total of 219 patients with newly diagnosed GBM who had received at least 3 cycles of adjuvant temozolomide (TMZ) followed by CCRT with TMZ were enrolled. Serial data on complete blood cell counts, including differential cell counts, were collected just before a new phase and before every treatment cycle of the regimen. Relationships between white blood cell (WBC) variable changes and treatment modalities as well as survival were analyzed. Lymphopenia was classified using the definition of the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS A total of 92 patients (42.0%) showed decreased levels of lymphocytes (< 1500/µL) at baseline. The WBC count, absolute neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio were all significantly decreased after RT/TMZ treatment and did not recover during the adjuvant TMZ period. However, these metrics all began to recover 3 months after the last TMZ cycle, except for the lymphocyte count. The proportion of lymphopenia patients (< 1500 lymphocytes/µL) increased to 74.8% after RT/TMZ and remained steady at approximately 71.5% (range 63.7-75.3%) throughout the management period. Moreover, the number of patients with grade 3 lymphopenia (< 500 lymphocytes/µL) also increased significantly after treatment to reach 2.9% (from 0.9% at baseline). Statistically, 75.7% of lymphopenia patients were predicted to recover in a median time of 240.3 days (95% confidence interval ± 104.7 days) after TMZ withdrawal. There were no dose-dependent relationships between RT or TMZ and lymphopenia. Grade 3 (< 500 lymphocytes/µL) lymphopenia measured at 1 month after RT/TMZ predicted significantly reduced survival (13.0 months vs. 19.5 months, p = 0.011).
CONCLUSION Lymphopenia is a frequent event during GBM disease progression and treatment. Treatment-related lymphopenia is profound and prolonged and can be used as a prognostic factor for GBM patients.
PubMed IF 3.4 혈액종양내과
1462019

제1저자 송진희 · 교신저자 김나영

, , , , , , , , ,
Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice.
Biochem Pharmacol. 2019;164:139-151.

Abstract
Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Clinical symptoms and histological severity of colitis and the levels of inflammatory mediators were evaluated in the colon of AOM/DSS-treated ovariectomized (OVX) mice. The levels of E2, myeloperoxidase (MPO), and NF-κB-dependent cytokines (interleukin (IL)-1β and IL-6) were measured by ELISA. Furthermore, quantitative real-time (qRT) PCR and Western blot analysis were performed. Ovariectomy did not aggravate AOM/DSS-induced colitis at 2 weeks. At weeks 10 and 16, ovariectomy significantly increased tumor number and incidence rate in only the proximal colon after AOM/DSS treatment (F_AOM/DSS vs OVX_AOM/DSS), and these increases were significantly reduced by E2 supplementation (OVX_AOM/DSS vs OVX_AOM/DSS/E2). However, ovariectomy did not affect CRC development in the distal colon (F_AOM/DSS vs OVX_AOM/DSS). At week 2, E2 administration to AOM/DSS-treated OVX mice attenuated the histological severity of colitis by decreasing the protein and/or mRNA levels of estrogen receptor alpha (ERα) and NF-κB-related mediators (i.e., COX-2, TNF-α, and IL-6) and by enhancing estrogen receptor beta (ERβ) and nuclear Nrf2 protein expression and the mRNA expression of related antioxidant enzyme genes (i.e., HO-1, GCLC, GCLM, and NQO1). Endogenous estrogen in females protects against the development of proximal colon cancer, and exogenous E2 replacement in OVX female mice showed protective effects against AOM/DSS-induced colitis and carcinogenesis. The mechanism could involve modulating ERs-, NF-κB- and Nrf2-mediated pathways.
PubMed IF 6.5 소화기내과
1452019

제1저자 박은숙, 이아람, 김두현, 이정훈 · 교신저자 이정훈, 김균환

, , , , , , , , , , , , , , , , , , , , , , , , ,
Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients.
J Hepatol. 2019;70(6):1093-1102.

Abstract
BACKGROUND & AIMS Tenofovir disoproxil fumarate (TDF) is one the most potent nucleot(s)ide analogues for treating chronic hepatitis B virus (HBV) infection. Phenotypic resistance caused by genotypic resistance to TDF has not been reported. This study aimed to characterize HBV mutations that confer tenofovir resistance.
METHODS Two patients with viral breakthrough during treatment with TDF-containing regimens were prospectively enrolled. The gene encoding HBV reverse transcriptase was sequenced. Eleven HBV clones harboring a series of mutations in the reverse transcriptase gene were constructed by site-directed mutagenesis. Drug susceptibility of each clone was determined by Southern blot analysis and real-time PCR. The relative frequency of mutants was evaluated by ultra-deep sequencing and clonal analysis.
RESULTS Five mutations (rtS106C [C], rtH126Y [Y], rtD134E [E], rtM204I/V, and rtL269I [I]) were commonly found in viral isolates from 2 patients. The novel mutations C, Y, and E were associated with drug resistance. In assays for drug susceptibility, the IC₅₀ value for wild-type HBV was 3.8 ± 0.6 µM, whereas the IC₅₀ values for CYE and CYEI mutants were 14.1 ± 1.8 and 58.1 ± 0.9 µM, respectively. The IC₉₀ value for wild-type HBV was 30 ± 0.5 µM, whereas the IC₉₀ values for CYE and CYEI mutants were 185 ± 0.5 and 790 ± 0.2 µM, respectively. Both tenofovir-resistant mutants and wild-type HBV had similar susceptibility to the capsid assembly modulator NVR 3-778 (IC₅₀ <0.4 µM vs. IC₅₀ = 0.4 µM, respectively).
CONCLUSIONS Our study reveals that the quadruple (CYEI) mutation increases the amount of tenofovir required to inhibit HBV by 15.3-fold in IC₅₀ and 26.3-fold in IC₉₀. These results demonstrate that tenofovir-resistant HBV mutants can emerge, although the genetic barrier is high.
LAY SUMMARY Tenofovir is the most potent nucleotide analogue for the treatment of chronic hepatitis B virus infection and there has been no hepatitis B virus mutation that confers >10-fold resistance to tenofovir up to 8 years. Herein, we identified, for the first time, a quadruple mutation that conferred 15.3-fold (IC₅₀) and 26.3-fold (IC₉₀) resistance to tenofovir in 2 patients who experienced viral breakthrough during tenofovir treatment.
PubMed IF 40.1 소화기내과
1442019

제1저자 이동화 · 교신저자 임수

, , , , , , , ,
Effect of cilostazol, a phosphodiesterase-3 inhibitor, on coronary artery stenosis and plaque characteristics in patients with type 2 diabetes: ESCAPE study.
Diabetes Obes Metab. 2019;21(6):1409-1418.

Abstract
AIM To perform a prospective study to evaluate the effect of cilostazol (CTZ) compared with aspirin (acetylsalicylic acid; ASA) in Korean people with diabetes and subclinical coronary atherosclerosis.
MATERIALS AND METHODS A total of 100 people with diabetes who had mild to moderate coronary atherosclerosis, assessed by coronary computed tomographic angiography (CCTA), were randomly assigned to either 200 mg/d CTZ or 100 mg/d ASA (n = 50 each group). The primary outcome was change in coronary artery stenosis assessed by CCTA after 12 months of treatment. Secondary outcomes included changes in plaque composition, coronary artery calcium score and cardiac markers.
RESULTS The mean age, body mass index and glycated haemoglobin concentration were 61.5 years, 25.0 kg/m² and 56.8 mmol/mol, respectively, and were well matched between the two groups. Coronary artery stenosis decreased in the CTZ group (from 44.0 ± 2.1% to 40.4 ± 2.5%) but remained unchanged in the ASA group (from 38.9 ± 2.1% to 40.6 ± 2.1%). In the CTZ group, the non-calcified portion of plaques decreased significantly (from 20.6 ± 3.0 to 17.3 ± 3.0 mm³ ), whereas it did not change significantly in the ASA group (15.2 ± 2.8 vs 16.6 ± 2.9 mm³ ). Increases in HDL cholesterol, decreases in triglycerides, liver enzyme and high-sensitivity C-reactive protein levels, and reductions in abdominal visceral fat area and insulin resistance were observed only in the CTZ group.
CONCLUSION CTZ treatment for 12 months decreased coronary artery stenosis and the non-calcified plaque component. These results suggest that CTZ treatment may be an option for preventing the progression of coronary atherosclerosis in people with diabetes.
PubMed IF 6.1 내분비대사내과
1432019

제1저자 박하람 · 교신저자 안용운, 김태민

, , , , , , , , ,
NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors.
Cytotherapy. 2019;21(6):603-611.

Abstract
BACKGROUND Treatment with tyrosine kinase inhibitors (TKIs) has improved the outcomes for patients with non-small cell lung cancer (NSCLC) harboring targetable driver mutations. However, acquired resistance to TKIs invariably develops within approximately 1 year of treatment by various mechanisms, including gatekeeper mutations, alternative pathway activation and histological transformations. Because immunotherapy is an option for patients with drug-resistant cancers, we generated several TKI-resistant NSCLC cell lines in vitro, and then evaluated the cytotoxicity of NK92-CD16 cells to these resistant cells.
MATERIALS AND METHODS TKI-resistant NSCLC cells (H3122CR1, H3122LR1, H3122CR1LR1, PC-9GR, PC-9ER, EBC-CR1 and EBC-CR2) were established from NCI-H3122 (EML4-ALK fusion), PC-9 (EGFR exon19 deletion) and EBC-1 (MET amplification) after continuous exposure to crizotinib, ceritinib, gefitinib, erlotinib and capmatinib. Expression of ligands for natural killer (NK) cell receptors and total EGFR were analyzed using flow cytometry. NK cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) using anti-EGFR monoclonal antibody (mAb) cetuximab were measured using NK92-CD16 as effectors and detected using the ⁵¹Chromium-release assay.
RESULTS We found that NK92-CD16 cells preferentially killed TKI-resistant NSCLC cells when compared with their parental NSCLC cells. Mechanistically, intracellular adhesion molecule 1 (ICAM-1) was up-regulated in the TKI-resistant NSCLC cells and patients' tumors, and the ICAM-1 up-regulated cancer cells lines were less susceptible to NK cytotoxicity by blocking ICAM-1. Moreover, NK92-CD16 cell-induced cytotoxicity toward TKI-resistant NSCLC cells was enhanced in the presence of cetuximab, an EGFR-targeting mAb.
CONCLUSION These data suggest that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC.
PubMed IF 4.5 혈액종양내과
1422019

제1저자 권영재 · 교신저자 김나영

, , , , , , , , , ,
The prevalence of histologic atrophy and intestinal metaplasia in the corpus has decreased over 15 years in females in the Korean population.
Helicobacter. 2019;24(3):e12579.

Abstract
BACKGROUND The aim of this study was to investigate the trends of atrophy and intestinal metaplasia (IM) in 2002 subjects without significant gastroduodenal diseases.
MATERIALS AND METHODS A total of 2002 subjects were prospectively enrolled and divided into three periods (2003-2007, 2008-2012, and 2013-2018). Trends of H pylori and atrophy/IM scored by Updated Sydney System were analyzed according to sex, and multivariate logistic analysis was performed for the risk factors for atrophy/IM.
RESULTS H pylori-negative and H pylori-positive subjects were 1220 (61.0%) and 782 (38.0%), respectively. H pylori positivity decreased from 149/303 (49.2%), 207/515 (40.2%) and 426/1184 (36.0%), in the three periods, respectively (P < 0.001). The prevalence of atrophy (P < 0.001) and IM in the corpus (P < 0.001) significantly decreased over 15 years in females, but not in males. The mean grade of atrophy and IM was higher in males (0.36 and 0.51) than in females (0.28 and 0.41) in the corpus (P = 0.027) and in the antrum (P = 0.006), respectively. Similarly, the mean grade of IM in males (0.34) was higher in females (0.19; P < 0.001) in the corpus. Multivariate analysis showed that old age, study period, and H pylori were statistically significant in atrophy of antrum and corpus, and IM in the corpus. In cases of IM of antrum, old age, H pylori, and smoking were statistically significant.
CONCLUSION A significant decrease in atrophy and IM in the corpus in females over 15 years suggests sex- or gender-specific characteristics.
PubMed IF 4.6 소화기내과
1412019

제1저자 김범석 · 교신저자 이근욱, 이세훈

, , , , , , , , , , , , , ,
A Phase II Study of Genexol-PM and Cisplatin as Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.
Oncologist. 2019;24(6):751-e231.

Abstract
LESSONS LEARNED Induction chemotherapy with Genexol-PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma.
BACKGROUND Genexol-PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol-PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
METHODS Patients received Genexol-PM (230 mg/m²) and cisplatin (60 mg/m²) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m²) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC.
RESULTS Of 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3-69.3). Although there was one treatment-related death, toxicity profiles to Genexol-PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty-one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow-up of 39 months, estimates of progression-free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively.
CONCLUSION IC with Genexol-PM and cisplatin demonstrated modest tumor response with well-tolerated toxicity profiles for patients with LA-HNSCC.
PubMed IF 4.7 혈액종양내과
1402019

제1저자 김충종, 송경호 · 교신저자 김의석, 박경화

, , , , , , , , , , , , , , , , ,
Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.
Clin Microbiol Infect. 2019;25(6):723-732.

Abstract
OBJECTIVES To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.
METHODS We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.
RESULTS Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05).
CONCLUSIONS Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
PubMed IF 8.7 감염내과
1392019

제1저자 송영신 · 교신저자 박영주

, , , , , , , , , ,
Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer.
Endocr Relat Cancer. 2019;26(6):629-641.

Abstract
Synergistic effects of BRAFV600E and TERT promoter mutations on the poor clinical outcomes in papillary thyroid cancer (PTC) have been demonstrated. The potential mechanism of this phenomenon has been proposed: MAPK pathway activation by the BRAFV600E mutation may upregulate E-twenty six (ETS) transcription factors, increasing TERT expression by binding to the ETS-binding site generated by the TERT promoter mutation; however, it has not yet been fully proven. This article provides transcriptomic insights into the interaction between BRAFV600E and TERT promoter mutations mediated by ETS factors in PTC. RNA sequencing data on 266 PTCs from The Cancer Genome Atlas and 65 PTCs from our institute were analyzed for gene expression changes and related molecular pathways, and the results of transcriptomic analyses were validated by in vitro experiments. TERT mRNA expression was increased by the coexistence of BRAFV600E and TERT promoter mutations (fold change, 16.17; q-value = 7.35 × 10-12 vs no mutation). In the ETS family of transcription factors, ETV1, ETV4 and ETV5 were upregulated by the BRAFV600E/MAPK pathway activation. These BRAFV600E-induced ETS factors selectively bound to the mutant TERT promoter. The molecular pathways activated by BRAFV600E were further augmented by adding the TERT promoter mutation, and the pathways related to immune responses or adhesion molecules were upregulated by TERT expression. The mechanism of the synergistic effect between BRAFV600E and TERT promoter mutations on cancer invasiveness and progression in PTC may be explained by increased TERT expression, which may result from the BRAF-induced upregulation of several ETS transcription factors.
PubMed IF 4.4 내분비대사내과
1382019

제1저자 최영훈 · 교신저자 이상협

, , , , , , , ,
A High Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Advanced Gallbladder Cancer Receiving Chemotherapy.
Cancer Epidemiol Biomarkers Prev. 2019;28(6):1045-1051.

Abstract
BACKGROUND Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined.
METHODS From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R.
RESULTS Patients with high MLR (>0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397-3.157; P < 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664-3.856; P < 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points.
CONCLUSIONS MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker.
IMPACT MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy.
PubMed IF 3.7 소화기내과
1372019

제1저자 이소령 · 교신저자 최의근

, , , , , ,
Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Supranormal Renal Function.
Stroke. 2019;50(6):1480-1489.

Abstract
Background and Purpose- In clinical trials, the reduced efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention was reported for patients with nonvalvular atrial fibrillation with a creatinine clearance (CrCl) >95 mL/min compared with that of warfarin. We examined the effectiveness, safety, and net clinical benefit of NOACs compared with warfarin in Asian patients with atrial fibrillation and supranormal renal function. Methods- Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, we included patients with nonvalvular atrial fibrillation with CrCl >80 mL/min. Among these incident oral anticoagulant users with rivaroxaban (n=6297), dabigatran (n=4241), apixaban (n=3395), edoxaban (n=1187), and warfarin (n=9884) were analyzed. Propensity score weighting was used to balance covariates across study groups. Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome defined as ischemic stroke+intracranial hemorrhage+gastrointestinal bleeding+all-cause death were analyzed using Cox regression analysis with warfarin as the reference. Results- Baseline characteristics were well balanced among all groups (mean age, 66±11 years; 63% were men; mean CHA₂DS₂-VASc score, 3.0±1.8). Forty-five percent of the patients had CrCl >95 mL/min. Pooled NOACs yielded lower risks of ischemic stroke (hazard ratio, 0.51; 95% CI, 0.43-0.60) and the composite outcome (hazard ratio, 0.64; 95% CI, 0.58-0.70) than warfarin in patients with CrCl >80 mL/min. These benefits were consistent in those with CrCl >95 mL/min. All 4 NOACs reduced the risks of ischemic stroke and the composite outcome in both patients with CrCl >80 mL/min and >95 mL/min. Conclusions- The NOACs showed better effectiveness and safety than warfarin in the patients with atrial fibrillation and supranormal renal function; this was consistently observed for all 4 NOACs and in patients with CrCl >95 mL/min.
PubMed IF 11.1 6.239
1362019

제1저자 고성준 · 교신저자 이국래

, , , , , , ,
Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.
Eur J Nutr. 2019;58(4):1603-1613.

Abstract
PURPOSE Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer.
METHODS COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10^-/- mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption.
RESULTS WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10^-/- mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC).
CONCLUSIONS WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.
PubMed IF 4.5 소화기내과
1352019

제1저자 정고은 · 교신저자 김영선

, , , , , , , ,
Dietary patterns are associated with the prevalence of nonalcoholic fatty liver disease in Korean adults.
Nutrition. 2019;62:32-38.

Abstract
OBJECTIVES There is minimal research on the effect of overall dietary patterns on the development of nonalcoholic fatty liver disease (NAFLD) in the Korean population. The present study investigated the association between dietary patterns and NAFLD.
METHODS A prospective cross-sectional study was performed on participants who visited a health care center for a health checkup. A semiquantitative food frequency questionnaire was administered to the participants to assess their food intake, and factor analysis was used to identify dietary patterns. Relationships between the dietary patterns and the risk of NAFLD were evaluated.
RESULTS A total of 331 of the 1190 participants (27.8%) analyzed were diagnosed with NAFLD. Three factors were generated and defined as the traditional pattern, Western and high-carbohydrate pattern, and simple meal pattern using a factor analysis procedure. The traditional pattern revealed a positive correlation with NAFLD, and the simple meal pattern exhibited an inverse correlation with NAFLD. We adjusted for confounding factors, such as age, sex, waist circumference, smoking status, total energy intake, diabetes, and hypertension, and participants in the highest quartile of the traditional dietary pattern exhibited a higher prevalence of NAFLD (P for trend = 0.0373; odds ratio, 1.85; 95% confidence interval, 1.11-3.08) than participants in the lowest quartile. Participants in highest quintile of the simple meal pattern exhibited a decreased risk of NAFLD compared with the lowest quintile (P for trend = 0.0233; odds ratio 0.59; 95% confidence interval 0.34-1.00).
CONCLUSIONS The traditional dietary pattern was associated with an increased risk of NAFLD, and the simple meal pattern was associated with a decreased risk of NAFLD in the Korean population. This finding supports the use of dietary patterns to predict the risk of NAFLD and potentially serve as a dietary prevention strategy in individuals who are at high risk of developing NAFLD.
PubMed IF 3.6 소화기내과
1342019

제1저자 강은정 · 교신저자 윤형진, 이하정

, , , , , , , , , , , ,
Acute kidney injury predicts all-cause mortality in patients with cancer.
Cancer Med. 2019;8(6):2740-2750.

Abstract
BACKGROUND Acute kidney injury (AKI) is a critical issue in cancer patients because it is not only a morbid complication but also able to interrupt timely diagnostic evaluation or planned optimal treatment. However, the impact of AKI on overall mortality in cancer patients remains unclear.
METHODS We conducted a retrospective cohort study of 67 986 cancer patients, from 2004 to 2013 to evaluate the relationship between AKI and all-cause mortality. We used KDIGO AKI definition and grading system.
RESULTS During 3.9 ± 3.1 years of follow-up, 33.8% of the patients experienced AKI at least once. Among AKI events, stage 1, 2, and 3 was 71.0%, 13.8%, and 15.1%, respectively. AKI incidence was highest in hematologic malignancies, followed by urinary tract cancer, and hepatocellular carcinoma. Male sex, older age, underlying diabetes and hypertension, lower serum albumin and plasma hemoglobin, more frequent radio-contrast exposure, entrance of clinical trials, and receiving chemotherapy were associated with AKI occurrence. AKI development was an independent risk factor for elevated mortality in cancer patients with dose-responsive manner (Stage 1, hazard ratio [HR] 1.183, 95% confidence interval [CI] 1.145-1.221, P < 0.001; Stage 2, HR 1.710, 95% CI 1.629-1.796; Stage 3, HR 2.000, 95% CI 1.910-2.095; No AKI, reference group) even after adjustment. This tendency was reproduced in various cancer types except thyroid cancer and in various treatment modalities, however, not shown in patients with baseline renal dysfunction.
CONCLUSION AKI was an independent risk factor for all-cause mortality in overall cancer patients with dose-responsive manner.
PubMed IF 3.5 신장내과
1332019

제1저자 구영도 · 교신저자 박경수

, , , , , , , , ,
SUMO-specific protease 2 mediates leptin-induced fatty acid oxidation in skeletal muscle.
Metabolism. 2019;95:27-35.

Abstract
BACKGROUND AND PURPOSE In addition to the central nervous system-mediated action, leptin also directly induces fatty acid oxidation in skeletal muscle. Rapid induction of FAO by leptin is mediated by the AMP-activated protein kinase (AMPK) pathway, but the mechanism of prolonged FAO by leptin was previously unknown. In an earlier study, we showed that free fatty acids increase transcription of small ubiquitin-like modifier (SUMO) specific protease 2 (SENP2) in skeletal muscle, and that SENP2 stimulates expression of FAO-associated enzymes by deSUMOylating peroxisome proliferator-activated receptors, PPARδ and PPARγ. In this study, we examine whether SENP2 is involved in prolonged stimulation of FAO by leptin.
METHODS The Effect of leptin on expression of SENP2 and on SENP2-mediated FAO was investigated by using western blotting and real time qPCR of C2C12 myotubes, and of C2C12 myotubes in which expression of specific genes was knocked down using siRNAs. Additionally, muscle-specific SENP2 knockout mice were generated to test the involvement of SENP2 in leptin-induced FAO in vivo.
RESULTS We show that leptin treatment of C2C12 myotubes causes signal transducer and activator of transcription 3 (STAT3) to bind to the Senp2 promoter, inducing SENP2 expression. We also show that leptin increases the binding of PPARδ and PPARγ to PPRE sites in the promoters of two FAO-associated genes: long-chain acyl-CoA synthetase 1 (Acsl1) or carnitine palmitoyl transferase 1b (Cpt1b). When SENP2 is knocked down in myotubes, leptin-induced expression of FAO-associated enzymes and prolonged increase of FAO are suppressed, but rapid increase of FAO is unaffected. In addition, leptin-induced expression of FAO-associated enzymes was not observed in muscle tissue of SENP2 knockout mice.
CONCLUSIONS We demonstrate that the peripheral actions of leptin on FAO are mediated by two different pathways: AMPK causes a rapid increase in FAO, and SENP2 of the STAT3 pathway causes a slow, prolonged increase in FAO.
PubMed IF 16.7 순환기내과
1322019

제1저자 윤준식, 송병근 · 교신저자 이정훈

, , , , , , , , , , , ,
Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data.
BMC Cancer. 2019;19(1):523.

Abstract
BACKGROUND Several randomized controlled trials have shown that adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells prolongs recurrence-free survival (RFS) after curative treatment for hepatocellular carcinoma (HCC). We investigated the efficacy of adjuvant immunotherapy with activated CIK cells in real-world clinical practice.
METHODS A total of 59 patients who had undergone curative surgical resection or radiofrequency ablation for stage I or II HCC, and subsequently received adjuvant CIK cell immunotherapy at two large-volume centers in Korea were retrospectively included. Propensity score matching with a 1:1 ratio was conducted to avoid possible bias, and 59 pairs of matched control subjects were also generated. The primary endpoint was RFS and the secondary endpoints were overall survival and safety.
RESULTS The median follow-up duration was 28.0 months (interquartile range, 22.9-42.3 months). In a univariable analysis, the immunotherapy group showed significantly longer RFS than the control group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.80; log-rank P = 0.006). The median RFS in the control group was 29.8 months, and the immunotherapy group did not reach a median RFS. A multivariable Cox proportional hazard analysis showed that immunotherapy was an independent predictor for HCC recurrence (adjusted HR, 0.38; 95% CI, 0.20-0.73; P = 0.004). The overall incidence of adverse events in the immunotherapy group was 16/59 (27.1%) and no patient experienced a grade 3 or 4 adverse event.
CONCLUSIONS The adjuvant immunotherapy with autologous CIK cells after curative treatment safely prolonged the RFS of HCC patients in a real-world setting.
PubMed IF 4.1 소화기내과
1312019

제1저자 안창호 · 교신저자 임수

,
Effects of Thiazolidinedione and New Antidiabetic Agents on Stroke.
J Stroke. 2019;21(2):139-150.

Abstract
Patients with hyperglycemia are at a high risk of cardio- and cerebrovascular diseases. Diabetes patients also have poor outcomes after cerebrovascular disease development. Several classes of drugs are used for diabetes management in clinical practice. Thiazolidinedione (TZD) was introduced in the late 1990s, and new antidiabetic agents have been introduced since 2000. After issues with rosiglitazone in 2007, the U.S. Food and Drug Administration strongly recommended that trials investigating cardiovascular risk associated with new antidiabetic medications should be conducted before drug approval in the United States, to prove the safety of these new drugs and to determine their superiority to previous medications. Currently, results are available from two studies with TZD focusing on cardiovascular diseases, including stroke, and from 12 cardiovascular outcome trials focusing on major adverse cardiovascular events associated with new antidiabetic agents (four with dipeptidyl peptidase-4 inhibitors, three with sodium-glucose cotransporter-2 inhibitors, and five with glucagon-like peptide-1 analogues). These studies showed different results for primary cardiovascular outcomes and stroke prevention. It is important to determine whether prescription of TZD or new antidiabetic medications compared to conventional treatment, such as sulfonylurea or insulin, is better for stroke management. Furthermore, it is unclear whether drugs in the same class show greater safety and efficacy than other drugs for stroke management.
PubMed IF 11 내분비대사내과
1302019

제1저자 김혜미 · 교신저자 손대원

, ,
Prevalence of Positive 99 mTc-DPD Scintigraphy as an Indicator of the Prevalence of Wild-type Transthyretin Amyloidosis in the Elderly.
Int Heart J. 2019;60(3):643-647.

Abstract
Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis, ^{99 m}Tc-DPD scintigraphy (DPD scan) is a useful diagnostic modality for wtTTR amyloidosis.We retrospectively analyzed patients older than 30 years who underwent DPD scanning for non-cardiac reasons at our hospital between June 2014 and March 2017 (n = 9,581). Transthoracic echocardiography was used to assess left ventricular hypertrophy (LVH), as well as systolic and diastolic function.A positive DPD scan was observed in only six patients (0.06%). All six of these patients were older than 70 years, and they constitute only 0.4% of patients in this age group (6/1652). Among the patients with a positive DPD scan, four showed concentric LVH and two showed a normal wall thickness. With respect to the severity of diastolic dysfunction and pulmonary artery pressure, patients with a positive DPD scan showed the expected E' and pulmonary artery systolic pressure for their age.Even considering the limited sensitivity of a positive DPD scan detecting wtTTR amyloidosis, the incidence of a positive DPD scan in non-cardiac patients indicated that wtTTR amyloid deposition does not seem to be a major cause for age-related diastolic dysfunction, nor does appear to have a high incidence in patients with heart failure with preserved EF in the elderly.
PubMed IF 1.4 순환기내과
1292019

제1저자 양한모, 진수련화, 장현덕 · 교신저자 김효수

, , , , , ,
Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase.
Sci Rep. 2019;9(1):7769.

Abstract
Sildenafil is known to reduce cardiac hypertrophy through cGMP-dependent protein kinase (cGK) activation. Studies have demonstrated that cGK has a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to vascular injury. Here, we aimed to examine the effects of cGK activation by sildenafil on neointimal formation and platelet aggregation. After vascular injury, neointimal hyperplasia in rat carotid arteries was significantly reduced in the sildenafil-treated group. This effect of sildenafil was accompanied by the reduction of viability and migration of VSMCs. Further experiments showed that the increased cGK activity by sildenafil inhibited platelet-derived growth factor-induced phenotype change of VSMCs from a contractile form to a synthetic one. Conversely, the use of cGK inhibitor or gene transfer of dominant-negative cGK reversed the effects of sildenafil, increasing viability of VSMCs and neointimal formation. Interestingly, sildenafil significantly inhibited platelet aggregation induced by ADP or thrombin. This effect was reversed by cGK inhibitor, suggesting that sildenafil inhibits platelet aggregation via cGK pathway. This study demonstrated that sildenafil inhibited neointimal formation and platelet aggregation via cGK pathway. These results suggest that sildenafil could be a promising candidate for drug-eluting stents for the prevention of both restenosis and stent thrombosis.
PubMed IF 4.9 순환기내과
1282019

제1저자 김수정 · 교신저자 강혜련, 이종명

, , , , , , , , , ,
Carbonic anhydrase inhibitor-induced Stevens-Johnson syndrome/toxic epidermal necrolysis leads to extensive cutaneous involvement.
J Allergy Clin Immunol Pract. 2019;7(8):2851-2853.e2.

PubMed IF 6.6 알레르기내과
1272019

제1저자 박민찬 · 교신저자 송영욱

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.
Arthritis Res Ther. 2019;21(1):122.

Abstract
BACKGROUND To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA).
METHODS This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100.
RESULTS A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively).
CONCLUSIONS Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101.
TRIAL REGISTRATION ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.
PubMed IF 5.4 류마티스내과
1262019

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , , ,
Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease.
J Am Coll Cardiol. 2019;73(19):2413-2424.

Abstract
BACKGROUND Although the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)-defined HRPC.
OBJECTIVES The current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease.
METHODS A total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm², plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories.
RESULTS The proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group.
CONCLUSIONS Physiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438).
PubMed IF 22.3 순환기내과
1252019

제1저자 조은주/임상섭 · 교신저자 윤정환/박태성

, , , , , , , , , , ,
Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma.
Sci Rep. 2019;9(1):7536.

Abstract
Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.
PubMed IF 4.9 소화기내과
1242019

제1저자 유민수 · 교신저자 이상협

, , , , , , , , , , ,
Natural Course and Risk of Cholangiocarcinoma in Patients with Recurrent Pyogenic Cholangitis: A Retrospective Cohort Study.
Gut Liver. 2019;13(3):373-379.

Abstract
BACKGROUND/AIMS Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA.
METHODS From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Coxs proportional hazard regression model.
RESULTS Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023).
CONCLUSIONS In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.
PubMed IF 4.1 소화기내과
1232019

제1저자 최국환 · 교신저자 김주성

, , , , , , , , ,
Risk of Anxiety and Depression in Patients with Inflammatory Bowel Disease: A Nationwide, Population-Based Study.
J Clin Med. 2019;8(5):jcm8050654.

Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3.
RESULTS During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the HR for developing depression after a diagnosis of CD and UC was 2.09 and 2.00, respectively (p < 0.001). The risks of anxiety and depression in patients with IBD were higher compared to controls, except in those with diabetes mellitus, hypertension, and dyslipidemia, or who required immunomodulators and biologics within one year of the IBD diagnosis.
CONCLUSIONS The risk of anxiety and depression increased after a diagnosis of IBD compared to the general population.
PubMed IF 3.3 소화기내과
1222019

제1저자 송명진 · 교신저자 이상훈, 이춘택

, , , , , , , , , , , ,
Prognosis of Small Cell Lung Cancer with Idiopathic Pulmonary Fibrosis: Assessment according to GAP Stage.
J Oncol. 2019;2019:5437390.

Abstract
INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer development, and small cell lung cancer (SCLC) comprises 15-20% of lung cancers with IPF. The objective of this study was to investigate survival outcomes and treatment-related complications according to GAP (gender, age, and physiology) stage in patients having SCLC with IPF (SCLC-IPF).
MATERIALS AND METHODS Retrospectively collected data of SCLC-IPF patients from two tertiary care university hospitals in South Korea were reviewed. A total of 59 SCLC-IPF patients were identified and categorized according to GAP stage, which was proposed by Ley et al. in 2012 to predict the prognosis of IPF. Survival outcomes and treatment-related complications were compared between the two groups.
RESULTS In a total of 59 patients, the median age was 71 years and 58 (98.3%) were male. In a comparison of the median overall survival (OS) according to GAP stage, median OS of the advanced GAP stage group was significantly shorter than median OS of GAP stage I group (7.1 months vs. 16.1 months; p = 0.002). Treatment-related complications occurred more frequently in the advanced GAP stage group; advanced GAP stage was the only predictor that exhibited a significant association with the incidence of acute exacerbation of IPF.
CONCLUSIONS Inferior survival outcome and higher incidence of treatment-related pulmonary toxicities were noted in the advanced GAP stage group. Furthermore, advanced GAP stage was the only predictor of treatment-related acute exacerbation of IPF. Physicians should thus consider GAP stage, which reflects the severity of IPF, during treatment of SCLC-IPF.
PubMed IF 4.528 호흡기내과
1212019

제1저자 김지현 · 교신저자 강혜련, 김혜영

, , , , , , ,
Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages.
J Allergy Clin Immunol. 2019;143(5):1769-1782.e11.

Abstract
BACKGROUND Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the participation of other types of ILCs in the development of asthma remains unclear.
OBJECTIVE This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.
METHODS Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs.
RESULTS In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage-related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage-related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage-dominant profile.
CONCLUSION A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.
PubMed IF 11.2 알레르기내과
1202019

제1저자 서경진 · 교신저자 임석아, 이경훈

, , , , , , , , , , , , , ,
Prognostic effects of abnormal DNA damage response protein expression in breast cancer.
Breast Cancer Res Treat. 2019;175(1):117-127.

Abstract
PURPOSE We aimed to explore the expression of DNA damage response machinery proteins and their integrated prognostic value in different subgroups of breast cancer.
METHODS Expression of NBS1, BRCA1, BRCA2, ATM, and p53 was determined by immunohistochemistry in 419 surgically resected breast tumors.
RESULTS Loss of NBS1, BRCA1, ATM, and abnormal p53 expression was significantly associated with lower disease-free survival rates. Abnormal DNA damage response protein expression, defined as loss of any one of NBS1, BRCA1, ATM, and/or abnormal p53 expression, was observed in 258 of 399 evaluable cases (64.7%) and was significantly associated with higher tumor grade, larger tumor size, and ER-negative, and/or PR-negative status. Most patients with luminal B (86.1%), HER2-enriched (94.4%), and triple-negative (86.8%) breast cancers had abnormal DNA damage response protein expression. In contrast, abnormal DNA damage response protein expression was found in only 53.8% of luminal A tumors. Abnormal DNA damage response protein expression was associated with significantly lower 5-year disease-free survival rates in all patients (95.6% vs. 84.8%, p = 0.001), as well as in the luminal A subgroup (97.4% vs. 89.0%, p = 0.011). In multivariate analysis, abnormal DNA damage response protein expression remained an independent predictor of shorter disease-free survival for luminal A subtype (hazard ratio 3.14, 95% confidence interval 1.16-8.47; p = 0.024).
CONCLUSION Abnormal DNA damage response protein expression is found in most luminal B and HER2-enriched breast cancers as frequently as in triple-negative breast cancer. In the luminal A subtype, abnormal DNA damage response protein expression is an independent prognostic marker.
PubMed IF 3.3 혈액종양내과
1192019

제1저자 김어진 · 교신저자 김남중, 박경화

, , , , , , , , , , , ,
Comparison of pyogenic postoperative and native vertebral osteomyelitis.
Spine J. 2019;19(5):880-887.

Abstract
BACKGROUND CONTEXT Postoperative vertebral osteomyelitis (PVO) after spinal surgery is a clinical challenge. However, there is a paucity of evidence regarding the most likely etiologic organisms to guide the choice of empirical antibiotic therapy, and previous reports of treatment outcomes for PVO are scarce.
PURPOSE To compare the microbiology, clinical characteristics, and outcomes of pyogenic PVO with native vertebral osteomyelitis (NVO).
STUDY DESIGN Retrospective comparative study.
PATIENT SAMPLE Patients with microbiologically proven vertebral osteomyelitis from three university-affiliated hospitals in South Korea between January 2005 and December 2015 with follow-up of at least 12 months after completion of antibiotics or until the patient was transferred. Patients who had a spine operation in the same location within 1 year of diagnosis, and all patients with remnant implants at the time of the vertebral osteomyelitis diagnosis, were defined as having PVO. The remainder of the patients was considered to have NVO. Spinal operations included discectomy, laminectomy, arthrodesis, and instrumentation for stabilization of the spine.
OUTCOME MEASURES Overall mortality, neurologic outcomes, treatment failure, and relapse of infection.
METHODS Demographic data, comorbidities, presenting symptoms, microbiological data, radiographic characteristics, laboratory data (including white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein), surgical treatment, and neurologic outcomes for each patient were reviewed from electronic medical records and analyzed. Mortality rate, treatment failure, and relapse of infection were calculated for the two groups. Factors associated with treatment outcome were evaluated using univariate and multivariate logistic regression analyses.
RESULTS The study evaluated 104 patients with PVO and 441 patients with NVO. In PVO, the most common isolate was Staphylococcus aureus (34%, n=35), followed by coagulase-negative staphylococci (31%, n=32). In NVO, the most common isolates were S. aureus (47%, n=206) and streptococci (21%, n=94). Of the staphylococci, the proportion of methicillin-resistant strains was significantly higher in PVO than that in NVO (75% vs. 39%, p<.001). The proportion of patients with gram-negative bacilli was 14% in PVO and 20% in NVO. Pre-existing or synchronous nonspinal infection was observed more frequently in NVO than in PVO (33% vs. 13%, p<.001). Although the duration of antibiotic use was similar in both groups, surgery for infection control was performed more frequently in PVO. The mortality rate was similar in both groups. However, the treatment failure and relapse rates at 12 months were higher in the PVO group (23% vs. 13%, p=.009; 14% vs. 7%, p=.028, respectively). Methicillin-resistant S.aureus was significantly associated with treatment failure or relapse via logistic regression (odds ratio 3.01, 95% confidence interval [1.71-5.32], p<.001; odds ratio 2.78, 95% confidence interval [1.40-5.49], p=.003).
CONCLUSIONS Coverage of methicillin-resistant staphylococci should be considered when prescribing empirical antibiotics for PVO. Although surgery was performed more often in PVO than NVO, the treatment failure and relapse rates at 12 months were higher in PVO.
PubMed IF 5.1 감염내과
1182019

제1저자 박지석 · 교신저자 김형관, 박은아

, , , , , , ,
Coronary Computed Tomography Angiography for the Diagnosis of Vasospastic Angina: Comparison with Invasive Coronary Angiography and Ergonovine Provocation Test.
Korean J Radiol. 2019;20(5):719-728.

Abstract
OBJECTIVE To investigate the diagnostic validity of coronary computed tomography angiography (cCTA) in vasospastic angina (VA) and factors associated with discrepant results between invasive coronary angiography with the ergonovine provocation test (iCAG-EPT) and cCTA.
MATERIALS AND METHODS Of the 1397 patients diagnosed with VA from 2006 to 2016, 33 patients (75 lesions) with available cCTA data from within 6 months before iCAG-EPT were included. The severity of spasm (% diameter stenosis [%DS]) on iCAG-EPT and cCTA was assessed, and the difference in %DS (Δ%DS) was calculated. Δ%DS was compared after classifying the lesions according to pre-cCTA-administered sublingual nitroglycerin (SL-NG) or beta-blockers. The lesions were further categorized with %DS ≥ 50% on iCAG-EPT or cCTA defined as a significant spasm, and the diagnostic performance of cCTA on identifying significant spasm relative to iCAG-EPT was assessed.
RESULTS Compared to lesions without SL-NG treatment, those with SL-NG treatment showed a higher Δ%DS (39.2% vs. 22.1%, p = 0.002). However, there was no difference in Δ%DS with or without beta-blocker treatment (35.1% vs. 32.6%, p = 0.643). The significant difference in Δ%DS associated with SL-NG was more prominent in patients who were aged < 60 years, were male, had body mass index < 25 kg/m², and had no history of hypertension, diabetes, or dyslipidemia. Based on iCAG-EPT as the reference, the per-lesion-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cCTA for VA diagnosis were 7.5%, 94.0%, 60.0%, 47.1%, and 48.0%, respectively.
CONCLUSION For patients with clinically suspected VA, confirmation with iCAG-EPT needs to be considered without completely excluding the diagnosis of VA simply based on cCTA results, although further prospective studies are required for confirmation.
PubMed IF 6.1 순환기내과

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.