SCI 발표논문

2016년 247편

2472016

제1저자 최승진, 박상원 · 교신저자 오명돈

, , , , , , , , , , , , , , , , , , , , ,
Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015.
PLoS Negl Trop Dis. 2016;10(12):e0005264.

Abstract
BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea.
METHODS/PRINCIPAL FINDINGS SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed.
CONCLUSIONS SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.
PubMed IF 3.6 감염내과
2462016

제1저자 박준원 · 교신저자 이은영

, , , , , ,
Impact of Dose Tapering of Tumor Necrosis Factor Inhibitor on Radiographic Progression in Ankylosing Spondylitis.
PLoS One. 2016;11(12):e0168958.

Abstract
OBJECTIVE To investigate the impact of dose reduction of tumor necrosis factor inhibitor (TNFi) on radiographic progression in ankylosing spondylitis (AS).
METHODS One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models.
RESULTS Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results.
CONCLUSION A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.
PubMed IF 2.8 류마티스내과
2452016

제1저자 김경영 · 교신저자 김정희

, , , , , , , ,
Disentangling of Malignancy from Benign Pheochromocytomas/Paragangliomas.
PLoS One. 2016;11(12):e0168413.

Abstract
OBJECTIVE Many malignant tumors initially appear benign but subsequently exhibit extensive metastases. Early identification of malignant pheochromocytomas and paragangliomas (PPGLs) before metastasis is important for improved prognosis. However, there are no robust prognostic indices of recurrence and malignancy. The aim of this study was to identify the clinical and histopathological factors that predict malignant PPGLs.
DESIGN Retrospective follow-up study.
METHODS In this study, we included 223 patients with pathologically confirmed PPGLs who were treated between 2000 and 2015 at the Seoul National University Hospital in South Korea.
RESULTS Of these patients, 29 were diagnosed with malignancy, 12 of whom presented with metastatic lesions at the initial diagnosis while 17 developed metastases during follow-up. Nineteen patients with recurrent PPGLs consisted of ones with malignant PPGLs (n = 17) and multifocal PPGLs (n = 2) who had VHL and RET mutations. The mean age at presentation for malignant PPGLs was significantly younger than that for benign PPGLs (43.0 vs. 49.0 years, respectively; p = 0.023). Tumor size was not a distinguishing factor between malignant and benign PPGLs (5.0 vs. 4.5 cm, respectively; p = 0.316) nor did it predict recurrence. Of 119 patients with available pheochromocytoma of adrenal gland scaled score (PASS) data, those with malignant PPGLs presented PASS values ≥4. Of 12 parameters of PASS, necrosis, capsular invasion, vascular invasion, cellular monotony, high mitosis, atypical mitotic figures, and nuclear hyperchromasia were significant predictors of malignancy.
CONCLUSIONS Tumor size did not predict malignancy or recurrence of PPGLs. PPGL patients with characteristic pathologic findings and PASS ≥4 or germline mutations require close follow-up.
PubMed IF 2.8 내분비대사내과
2442016

제1저자 이지은 · 교신저자 임수

, , , , , , , , ,
Comprehensive assessment of lipoprotein subfraction profiles according to glucose metabolism status, and association with insulin resistance in subjects with early-stage impaired glucose metabolism.
Int J Cardiol. 2016;225:327-331.

Abstract
BACKGROUND Early detection of atherogenic dyslipidemia is crucial. We investigated lipoprotein subfraction parameters according to glucose metabolism status.
METHODS We recruited 1255 lipid-lowering drug-naïve subjects with normal fasting glucose (NFG; n=200, 15.9%), impaired fasting glucose (IFG; n=443, 35.3%), or type 2 diabetes (T2D; n=612, 48.8%). Lipoprotein subfractions (1-7) were determined by polyacrylamide gel electrophoresis, separating low-density lipoprotein (LDL) into large buoyant LDL (lbLDL, LDL1-2) and small dense LDL (sdLDL, LDL3-7). Lipoprotein subfraction parameters including the sdLDL% (LDL3-7/LDL1-7), the sdLDL/lbLDL ratio (LDL3-7/LDL1-2), and weighted LDL subfraction (LDLSF) scores, were compared between groups. Their associations with insulin resistance, estimated using the homeostasis model assessment of insulin resistance, were examined.
RESULTS The concentrations of sdLDL particles were significantly higher in subjects with T2D and IFG than in those with NFG (15.78±13.47mg/dl and 14.60±14.33mg/dl, respectively, vs. 12.22±12.31mg/dl). Compared with those with NFG, subjects with IFG or T2D had significantly a higher sdLDL% (15.98±15.26% vs. 19.50±16.21% or 21.46±16.81%, respectively), a higher sdLDL/lbLDL ratio (0.24±0.30 vs. 0.31±0.37 or 0.35±0.39), and a higher LDLSF score (2.08±0.91 vs. 2.30±1.14 or 2.36±1.17). These lipoprotein subfraction parameters had stronger associations with insulin resistance compared to conventional lipid profiles in the IFG and T2D groups.
CONCLUSIONS Atherogenic dyslipidemia is initiated in an early stage of impaired glucose metabolism, when early intervention might be required.
PubMed IF 3.3 내분비대사내과
2432016

제1저자 이상훈 · 교신저자 박무석

, , , , , , , , , , , , ,
Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions.
Lung Cancer. 2016;102:89-95.

Abstract
OBJECTIVES Disruption in the stability of respiratory microbiota is known to be associated with many chronic respiratory diseases. However, only few studies have examined microbiomes in lung cancer. Therefore, we characterized and compared the microbiomes of patients with lung cancer and those with benign mass-like lesions.
MATERIALS AND METHODS Bronchoalveolar fluid was collected prospectively to evaluate lung masses in patients who had undergone bronchoscopies from May to September 2015. Twenty-eight patients (20 male, 8 female) were enrolled: 20 diagnosed with lung cancer and 8 diagnosed with benign diseases. Samples were analysed by 16S rRNA-based next-generation sequencing.
RESULTS The participants' mean age was 64±11years. Bacterial operational taxonomic units were classified into 26 phyla, 44 classes, 81 orders, 153 families, 288 genera, and 797 species. The relative abundance of two phyla (Firmicutes and TM7) was significantly increased in patients with lung cancer (p=0.037 and 0.035, respectively). Furthermore, two genera (Veillonella and Megasphaera) were relatively more abundant in lung cancer patients (p=0.003 and 0.022, respectively). The area under the curve of a combination of these two genera used to predict lung cancer was 0.888 (sensitivity=95.0%, specificity=75.0% and sensitivity=70.0%, specificity=100.0%; p=0.002).
CONCLUSION The results indicate that differences exist in the bacterial communities of patients with lung cancer and those with benign mass-like lesions. The genera Veillonella and Megasphaera showed the potential to serve as biomarkers to predict lung cancer. Thus, the lung microbiota may change the environment in patients with lung cancer.
PubMed IF 5.3 호흡기내과
2422016

제1저자 이승아 · 교신저자 윤연이

, , , , , , , , , , , , , , , ,
Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.
Am J Cardiol. 2016;118(11):1647-1654.

Abstract
The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.
PubMed IF 2.5 순환기내과
2412016

제1저자 김학령 · 교신저자 김명아

, , , , , , , , ,
Sex Difference in the Association Between Metabolic Syndrome and Left Ventricular Diastolic Dysfunction.
Metab Syndr Relat Disord. 2016;14(10):507-512.

Abstract
BACKGROUND Sex-related differences in the influence of metabolic syndrome (MetS) on various cardiovascular diseases have been suggested. The aim of this study was to investigate the effect of sex on the association between MetS and left ventricular (LV) diastolic dysfunction in patients with suspected coronary artery disease (CAD).
METHODS Two hundred ten patients (105 men and age-matched 105 women; mean age: 56.5 ± 10.9 years) undergoing elective coronary angiography for the evaluation of CAD were studied. MetS was defined according to the International Diabetes Federation criteria. LV diastolic function was assessed using transthoracic echocardiography.
RESULTS The incidence of MetS was 23.8% in men and 14.3% in women (P = 0.079). The incidence of LV diastolic dysfunction was significantly different by MetS in women, but not in men. In multiple linear regression analyses, the number of MetS components was independently associated with septal e' velocity, E/e', and left atrial (LA) diameter in women (P < 0.05 for each). In men, the number of MetS components was associated with only LA size in this analysis. As the number of components of MetS increased, septal e' velocity decreased proportionally in women (P < 0.001), but not in men (P = 0.117).
CONCLUSIONS Among middle-aged and elderly Korean patients at high risk of CAD, the impact of MetS on LV diastolic dysfunction was more pronounced in women than in men. This suggests the important role of sex hormonal effects in the development of LV diastolic dysfunction in relation to MetS in this population.
PubMed IF 1.6 순환기내과
2402016

제1저자 강아름 · 교신저자 김정희

, , , , , , , , ,
Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group.
Pituitary. 2016;19(6):573-581.

Abstract
PURPOSE Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group.
METHODS A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII).
RESULTS The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m²) contributed to a higher risk of metabolic syndrome.
CONCLUSIONS The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.
PubMed IF 3.8 내분비대사내과
2392016

제1저자 오수연 · 교신저자 김나영

, , , , , ,
Effect of Helicobacter pylori Eradication and ABO Genotype on Gastric Cancer Development.
Helicobacter. 2016;21(6):596-605.

Abstract
BACKGROUND Evidence is lacking regarding how Helicobacter pylori infection status, eradication history, and ABO blood type affect the development of gastric cancer (GC) given the multifactorial and distinctive etiology according to cancer location (noncardia vs cardia) and histologic type (intestinal vs diffuse-type). We evaluated the effect of H. pylori infection status incorporated with H. pylori eradication history and ABO genotype on GC development according to cancer location and histologic type.
METHODS A case-control study of 997 patients with noncardia GC (NCGC) and 1147 control subjects was performed using risk analyses with 14 factors including H. pylori infection with eradication history and ABO genotype. As final analyses, multivariable logistic regression models were fitted. Additionally, H. pylori infection status with eradication history was tested for its association with age, atrophic gastritis (AG), and intestinal metaplasia (IM).
RESULTS The ABO genotype with the B allele was associated with a significantly lower risk of NCGC of both histologic types. The reduction in risk for NCGC by adding the B allele was more prominent in diffuse-type than that in the intestinal-type. H. pylori infection with eradication history was associated with a significantly lower risk of NCGC of both histologic types, compared with those without eradication history (odds ratio (OR), 0.22; 95% confidence interval (CI), 0.14-0.34) approaching that of uninfected subjects. Past infection status without an eradication history was associated with older age, AG, and IM.
CONCLUSIONS H. pylori eradication and the B allele decreased the risks of the intestinal and diffuse-types of NCGC. H. pylori eradication revealed a strong association against developing NCGC. Therefore, it should be considered as a primary measure in NCGC prevention.
PubMed IF 4.6 소화기내과
2382016

제1저자 곽낙원 · 교신저자 임재준

, , , , , ,
Non-tuberculous mycobacterial lung disease: diagnosis based on computed tomography of the chest.
Eur Radiol. 2016;26(12):4449-4456.

Abstract
OBJECTIVES To elucidate the accuracy and inter-observer agreement of non-tuberculous mycobacterial lung disease (NTM-LD) diagnosis based on chest CT findings.
METHODS Two chest radiologists and two pulmonologists interpreted chest CTs of 66 patients with NTM-LD, 33 with pulmonary tuberculosis and 33 with non-cystic fibrosis bronchiectasis. These observers selected one of these diagnoses for each case without knowing any clinical information except age and sex. Sensitivity and specificity were calculated according to degree of observer confidence. Inter-observer agreement was assessed using Fleiss' κ values. Multiple logistic regression was performed to elucidate which radiological features led to the correct diagnosis.
RESULTS The sensitivity of NTM-LD diagnosis was 56.4 % (95 % CI 47.9-64.7) and specificity 80.3 % (73.1-86.0). The specificity of NTM-LD diagnosis increased with confidence: 44.4 % (20.5-71.3) for possible, 77.4 % (67.4-85.0) for probable, 95.2 % (87.2-98.2) for definite (P < 0.001) diagnoses. Inter-observer agreement for NTM-LD diagnosis was moderate (κ = 0.453). Tree-in-bud pattern (adjusted odds ratio [aOR] 6.24, P < 0.001), consolidation (aOR 1.92, P = 0.036) and atelectasis (aOR 3.73, P < 0.001) were associated with correct NTM-LD diagnoses, whereas presence of pleural effusion (aOR 0.05, P < 0.001) led to false diagnoses.
CONCLUSIONS NTM-LD diagnosis based on chest CT findings is specific but not sensitive.
KEY POINTS • Diagnosis of NTM-LD based on radiological findings showed high specificity. • Sensitivity of NTM-LD diagnosis was around 50 %. • Inter- observer agreement was moderate. • Identification of tree-in-bud pattern, consolidation and atelectasis led to correct diagnoses.
PubMed IF 6 호흡기내과
2372016

제1저자 유정주 · 교신저자 윤정환

, , , , , , , ,
Differential sensitivity of hepatocellular carcinoma cells to suppression of hepatocystin transcription under hypoxic conditions.
J Bioenerg Biomembr. 2016;48(6):581-590.

Abstract
Mutations in the gene encoding hepatocystin/80 K-H (PRKCSH) cause autosomal dominant polycystic liver disease. Hepatocystin deficiency impairs glucosidase II activity, which is critical for processing and folding glycoproteins in the endoplasmic reticulum (ER). Hypoxia is known as a strong stimulus for generating survival signals in hepatocellular carcinoma (HCC) cells. However, hypoxia may induce cell apoptosis under conditions of severe ER stress. Thus, we hypothesized that suppression of hepatocystin transcription induces HCC cell death under hypoxic conditions due to excessive ER stress. A new human HCC cell line, SNU-3058, was established following primary culture of tumor cells harvested from a Korean patient with rapidly growing hypovascular HCC. In cell culture, human HCC cells (Huh-7, SNU-761, and SNU-3058) were treated with control siRNA or hepatocystin siRNA with or without doxorubicin under hypoxic conditions. Cell viability, ER stress, unfolded protein response (UPR), and apoptosis were assessed using the MTS assay, immunoblot assay, and RT-PCR. Suppression of hepatocystin transcription attenuated proliferation in Huh-7 and SNU-761 cells, while proliferation was amplified in SNU-3058 cells. Similar results were observed following treatment with doxorubicin. Hepatocystin siRNA transfection increased cell death in Huh-7 and decreased cell death in SNU-3058. In SNU-3058, hepatocystin siRNA amplified GRP78, known as a pro-survival and cyto-protective signal, and attenuated the pro-apoptotic signal CHOP. These findings suggest that suppression of hepatocystin transcription induce the UPR, which alleviates damage associated with ER stress in SNU-3058. UPR had a limited role in protecting SNU-761 cells, resulting in cell death through apoptosis. In addition, blocking of pro-survival UPR signal by bacitracin or GRP78 knockdown, attenuated hepatocystin siRNA-induced proliferation in SNU-3058 cells under hypoxia. In this study, we demonstrated that different sensitivities to hepatocystin siRNA among human HCC cell lines are dependent on appropriate UPRs to hypoxia-induced ER stress following hepatocystin siRNA transfection. Because UPR is the main evasive mechanism for apoptosis induced by suppression of hepatocystin, targeting hepatocystin via UPR suppression could be a strategy for treating HCC.
PubMed IF 3.7 소화기내과
2362016

제1저자 석기태, 윤정환 · 교신저자 배시현, 백순구

, , , , , , , , , , , , , , , , , , ,
Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial.
Hepatology. 2016;64(6):2185-2197.

Abstract
UNLABELLED Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 10⁷ BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups.
CONCLUSION Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).
PubMed IF 18 소화기내과
2352016

제1저자 하혜림 · 교신저자 오도연

, , , , , , , , , ,
Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy.
Oncotarget. 2016;7(47):76604-76612.

Abstract
Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy. Serum sPDL1 was measured using an enzyme-linked immunosorbent assay. Clinical data included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, neutrophil × platelet/lymphocyte). The patients were assigned to two cohorts (training and validation cohort) using a simple random sampling method to validate the cut-off value of each marker. Validation was performed using a twofold cross-validation method. Overall survival (OS) of all patients was 9.07 months (95% CI: 8.20-11.33). Median sPDL1 was 1.20 ng/mL (range 0.03-7.28, mean 1.50, SD 1.22). Median NLR, PLR and SII were 2.60, 142.85 and 584.93, respectively. Patients with high sPDL1 (≥0.94 ng/mL) showed worse OS than patients with low sPDL1 (7.93 vs. 14.10 months, HR 1.891 (1.35-2.65), p<0.001). In multivariate analysis, high sPDL1 and NLR were independent poor prognostic factors. In conclusion, serum sPDL1 can be measured and has significant role on the prognosis of advanced BTC patients treated with palliative chemotherapy.
PubMed IF 5.008 혈액종양내과
2342016

제1저자 이주연 · 교신저자 송영욱

, , , ,
Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response.
Arthritis Res Ther. 2016;18(1):264.

Abstract
BACKGROUND Exosomes are involved in intercellular communication. The aim of this study was to investigate whether circulating exosomes effectively contribute to the inflammatory response in systemic lupus erythematosus (SLE).
METHODS Exosomes were purified from SLE patients and healthy controls (HCs). Healthy peripheral blood mononuclear cells (PBMCs) were stimulated with exosomes isolated from SLE patients and HCs in the presence or absence of Toll-like receptor (TLR) inhibitors. Production of interferon (IFN)-α, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured. Correlation between exosome levels and SLE disease activity was examined.
RESULTS The serum exosomes levels were significantly higher in SLE patients than in HCs. SLE exosomes induced a higher production of IFN-α, TNF-α, IL-1β, and IL-6 compared to healthy exosomes. SLE serum that was depleted of exosomes and SLE exosomes that were mechanically disrupted failed to induce any significant cytokine production. Exosome-mediated production of TNF-α, IL-1β, and IL-6 was decreased by the TLR4 antagonist, whereas that of IFN-α was suppressed by the TLR1/2, TLR7, and TLR9 antagonists. Exosome levels correlated with disease activity in SLE patients (rho = 0.846, p = 0.008).
CONCLUSIONS The circulating exosomes are immunologically active and their levels correlate with disease activity in SLE patients. The circulating exosomes might serve as novel biomarkers of SLE disease activity.
PubMed IF 5.4 류마티스내과
2332016

제1저자 조유리 · 교신저자 유수종

, , , , , , , , , , , ,
Survival Analysis of Single Large (>5 cm) Hepatocellular Carcinoma Patients: BCLC A versus B.
PLoS One. 2016;11(11):e0165722.

Abstract
BACKGROUND & AIMS Single large (>5 cm) hepatocellular carcinoma (HCC) is classified as Barcelona Liver Clinic (BCLC) stage early stage (A). Yet, controversies exist whether single large HCC can be considered as early stage. We have analyzed long-term outcome to see which stage is appropriate for these patients.
METHODS From 2005 to 2006, 1,546 consecutive patients who were newly diagnosed as HCC (BCLC A or B) at four tertiary hospitals in Korea were analyzed. BCLC A was sub-classified into A1 (single 2-5 cm), A2 (2-3 nodules ≤3 cm), and A3 (single >5 cm). BCLC B1 included patients beyond-Milan criteria, and within up-to-7 criterion. Survival prediction between subgroupings (1: A1 + A2 + A3 vs. B1 and 2: A1 + A2 vs. A3 + B1) was compared based on c-index and Akaike information criterion (AIC).
RESULTS The 5-year overall survival (OS) rate was 62.3, 58.6, 36.8, and 42.0% for A1, A2, A3 and B1, respectively. In multivariate Cox-regression analysis, OS was significantly different between A3 + B1 vs. A1 + A2 (hazard ratio [HR] 1.85; P<0.001), but not between A1 + A2 + A3 vs. B1 (HR 1.19; P = 0.258). For A3, surgical resection showed superior OS over transarterial chemoembolization. Survival prediction was superior in subgrouping 2 (AIC 5727.2; c-index 0.652) than subgrouping 1 (AIC 5766.3; c-index 0.619) even after inverse probability weighting.
CONCLUSIONS This large scale long-term follow-up data shows that single large tumor should be considered as intermediate stage in terms of prognosis. However, in terms of treatment, resection might be the first line treatment option.
PubMed IF 2.8 소화기내과
2322016

제1저자 김연욱 · 교신저자 김덕겸

, , , , , , ,
The regional association between bronchiectasis and lung cancer in chest CT.
BMC Pulm Med. 2016;16(1):151.

Abstract
BACKGROUND Limited studies have examined the association between lung cancer and bronchiectasis (BE). This study evaluated the regional association between BE and lung cancer by analyzing the lobar location of lung cancer in patients with underlying BE.
METHODS This clustered multi-level study enrolled patients who had underlying BE and were newly diagnosed with lung cancer between January 1, 2010 and May 30, 2013 in two referral hospitals in South Korea. By analyzing the presence of lung cancer and underlying BE as event variables at the level of lung lobes on chest computed tomography (CT), we evaluated the association of BE and lung cancer by the locations of the diseases.
RESULTS Eighty-one patients with BE and combined lung cancer were enrolled. Within 486 lung lobes of the patients, combined BE and lung cancer in the same lobe was found in 11 lobes (2.3 %). Using the general estimating equation assuming BE as a risk factor of lung cancer, the results indicated that the prevalence of lung cancer was significantly lower in the lobes with pre-existing BE (β = -1.09, p-value = 0.001).
CONCLUSIONS Regionally, pre-existing BE was associated with a lower risk of the occurrence of lung cancer in the same lobe.
PubMed IF 3.1 호흡기내과
2312016

제1저자 이소령 · 교신저자 최의근

, , , , , , , , , ,
Evaluation of the association between diabetic retinopathy and the incidence of atrial fibrillation: A nationwide population-based study.
Int J Cardiol. 2016;223:953-957.

Abstract
BACKGROUND Atrial fibrillation (AF) is prevalent among type 2 diabetic patients. However, the association between diabetic retinopathy (DR) and AF is controversial.
METHODS We included 40,500 patients with type 2 diabetes (≥40years, mean age 62±11years, 53% men) without AF from the Korean National Insurance Service-National Sample Cohort (2002-2007). Subjects were classified without DR (non-DR, n=30,178), with DR (DR, n=8920), and with proliferative DR (PDR, n=1402).
RESULTS During a mean 5.9-year follow-up, 1261 (3.1%) patients were newly diagnosed as having AF (4.9, 6.0, and 8.3 per 1000 person-years in the non-DR, DR, and PDR groups, respectively). In multivariate Cox proportional hazard models, patients in the DR and PDR groups had a significantly higher risk of AF than those in the non-DR group (DR group: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.00-1.30; PDR group: HR 1.46, 95% CI 1.13-1.87); p for trend <0.001). The risk of AF increased in patients with DR and end-stage renal disease (ESRD) (HR 2.39, 95% CI 1.31-3.96, p<0.001) and in those with PDR and ESRD (HR 3.59, 95% CI 1.96-5.97, p<0.001) compared to those without DR and ESRD.
CONCLUSIONS The presence and severity of DR was significantly associated with the incidence of AF. Also, the presence of ESRD had an impact on the incidence of AF in patients with DR.
PubMed IF 3.3 순환기내과
2302016

제1저자 오세일 · 교신저자 오세일

, , , , , , , , , , , , ,
Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF registry.
Int J Cardiol. 2016;223:543-547.

Abstract
OBJECTIVE To compare the distribution of international normalized ratios (INRs) in patients receiving vitamin K antagonist (VKA) for newly diagnosed atrial fibrillation in Eastern and Southeastern Asia and in other regions of the world (ORW) represented in the ongoing, global observational study GARFIELD-AF.
METHODS AND RESULTS 3621 and 13,541 patients were recruited prospectively in 2010-2013 from Asia and ORW, respectively. At baseline, excluding patients with unknown antithrombotic treatment, 1356 (37.8%) in Asia and 7081 (53.3%) in ORW received VKA (±antiplatelets). INR readings during 1-year follow-up were analyzed for VKA-treated patients with ≥3 measurements (878 [64.7%] patients in Asia, 4452 [62.9%] in ORW). VKA-treated patients in Asia were younger than those in ORW (mean 67.1 vs 71.3years), with a lower CHA₂DS₂-VASc score (3.0 vs 3.5), but a similar HAS-BLED score (1.3 vs 1.4). Mean INR was lower in Asia than in ORW (2.0 vs 2.4). The proportion of time in the therapeutic range, defined using the multinational target of 2.0-3.0, was substantially lower in Asia (31.1% vs 54.1%). In Asia and ORW, 59.3% and 28.2% of INRs were <2, and 9.6% and 17.7% were >3, respectively. The same trend was found in different age groups (<65, 65-74, ≥75years).
CONCLUSION GARFIELD-AF data demonstrate a difference in the distribution of INRs in patients from Asia versus other regions under current real-world practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.
PubMed IF 3.3 순환기내과
2292016

제1저자 문민경 · 교신저자 박영주

, , , , , , , , , , ,
Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression.
Mol Cell Endocrinol. 2016;436:50-8.

Abstract
Thyroid-stimulating hormone (TSH) receptor is expressed in extrathyroidal tissues such as hepatocytes, adipocytes, and skeletal muscle, which suggests a possible novel role of TSH in various metabolic processes in extrathyroidal tissues independent of thyroid hormones. We investigated whether TSH has any effects on glucose tolerance and insulin sensitivity in the skeletal muscle using diet-induced obesity (DIO) mouse models and rodent skeletal muscle cells. TSH improved glucose tolerance in DIO mice and this was associated with an improvement of skeletal muscle insulin sensitivity resulting from the increased expression of insulin receptor substrate (IRS)-1 protein and mRNA therein. TSH significantly increased both basal and insulin-stimulated glucose transport in rat L6 myotubes and increased the expression of IRS-1 protein and mRNA in these cells as well. TSH also stimulated Irs1 promoter activation; this stimulation was abolished by protein kinase A (PKA) inhibition using H89 or by mutation of the cAMP-response element site located at -1155 to -875 bp of the Irs1 promoter region, supporting a novel role of TSH activated-cAMP/PKA/CREB signaling in the regulation of Irs1 expression. In conclusion, TSH improves insulin sensitivity in skeletal muscle by increasing Irs1 gene expression. This regulatory effect is mediated by a PKA-CREB-dependent pathway.
PubMed IF 3.4 내분비대사내과
2282016

제1저자 조준현 · 교신저자 정숙향

, , , , , , , , ,
Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.
World J Gastroenterol. 2016;22(42):9427-9436.

Abstract
AIM To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection.
METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome.
RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development.
CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.
PubMed IF 7.7 소화기내과
2272016

제1저자 양민석 · 교신저자 강혜련

, , , , , , , , ,
Incidence of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Nationwide Population-Based Study Using National Health Insurance Database in Korea.
PLoS One. 2016;11(11):e0165933.

Abstract
BACKGROUND Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases; however, it is hard to estimate their incidence due to the rarity of these diseases. We evaluated the incidence of SJS and TEN using a nationwide administrative database.
METHODS We used a national medical insurance review system (Health Insurance Review and Assessment) database which contained the claim data of the entire nation from 2009 to 2013 to estimate the accurate incidence of SJS and TEN in Korea. The diagnostic codes of L511 (SJS) or L512 (TEN) from the International Classification of Diseases-10th revision were used to define the target study population. We also retrospectively followed up a 2011 SJS and TEN cohort for 24 months in order to assess the in-hospital mortality, related complications and total claims cost due to SJS and TEN.
RESULTS A total of 1,167 (938 SJS and 229 TEN) cases were newly diagnosed from 2010 to 2013. The age- and sex-standardized annual incidences estimated in this study were 3.96 to 5.03 in SJS and 0.94 to 1.45 in TEN per million. There was no significant change in annual incidence throughout the study periods. When analyzed by 10-year age groups, the annual incidence was the lowest in group 20-29 years and the highest in group 70 for both SJS and TEN. Based on the 2011 cohort analysis, the in-hospital mortality were 5.7 and 15.1% for SJS and TEN, respectively. The mortality increased with age, particularly, after 40 years of age. Among the complications related with SJS or TEN, ocular sequelae was the most common (43.1 and 43.4% of SJS and TEN patients, respectively) followed by urethral sequelae (5.7 and 9.4% of SJS and TEN patients, respectively).
CONCLUSION Overall, our data suggest that SJS, and TEN are infrequent but constantly arise throughout the years.
PubMed IF 2.8 알레르기내과
2262016

제1저자 서경진 · 교신저자 김인호

, , , , , , , , , , , , , , , , , , , , ,
Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome.
PLoS One. 2016;11(11):e0166245.

Abstract
Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06-2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06-2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment.
PubMed IF 2.8 혈액종양내과
2252016

제1저자 김이경 · 교신저자 정혜승

, , , , , , , , ,
Serum bilirubin levels are positively associated with glycemic variability in women with type 2 diabetes.
J Diabetes Investig. 2016;7(6):874-880.

Abstract
AIMS/INTRODUCTION Glycemic variability is known to induce oxidative stress. We investigated the relationships between glycemic variability and serum bilirubin levels, an endogenous anti-oxidant, in patients with diabetes.
MATERIALS AND METHODS A cross-sectional study was carried out with 77 patients with type 2 diabetes who had been recruited to two clinical studies from 2008 to 2014. There were no participants with diseases of the pancreas, liver, biliary tract and chronic renal insufficiency. Glycemic variation was calculated by a continuous glucose monitoring system, and correlation analyses were carried out to evaluate their association with bilirubin levels. Multiple linear regression was carried out to identify independent factors influencing bilirubin levels and glycemic variation.
RESULTS Among the participants, 42.3% were men. The mean (standard deviation) age was 61.5 years (10.4 years), body mass index was 24.2 kg/m² (2.8 kg/m² ), diabetes duration was 17.7 years (9.5 years), hemoglobin A_1c was 60.7 mmol/mol (7.1 mmol/mol; 7.7 [0.7]%) and bilirubin was 11.8 μmol/L (4.10 μmol/L). Serum bilirubin levels were not different according to age, body mass index and hemoglobin A_1c . However, the mean amplitude of glucose excursion was positively associated with bilirubin levels in women (r = 0.588, P < 0.001). After adjustment with duration of diabetes, serum albumin, liver enzymes, and mean glucose, the correlation between bilirubin and mean amplitude of glucose excursion remained significant (r = 0.566, P < 0.001). Multiple linear regression analyses showed that bilirubin was an independent determinant for the mean amplitude of glucose excursion in women. 1,5-Anhydroglucitol was also associated with bilirubin levels in women.
CONCLUSIONS Bilirubin level within the physiological range might be an independent predictor for glycemic variability in women with type 2 diabetes.
PubMed IF 3.6 내분비대사내과
2242016

제1저자 이반석 · 교신저자 류지곤

, , , , , , , , ,
Reintervention for occluded metal stent in malignant bile duct obstruction: A prospective randomized trial comparing covered and uncovered metal stent.
J Gastroenterol Hepatol. 2016;31(11):1901-1907.

Abstract
BACKGROUND AND AIM No prospective data are available on comparing covered and uncovered self-expandable metal stent (SEMS) for reintervention of occluded uncovered metal stents during endoscopic retrograde cholangiopancreatography in patients with malignant distal biliary obstruction.
METHODS From June 2010 to November 2014, 43 patients with inoperable distal biliary obstruction of a previously placed uncovered SEMS were enrolled from three centers in Korea and randomly assigned to covered (n = 22) or uncovered SEMS group (n = 21). The primary outcome was overall stent patency. Secondary outcome was time-to-stent occlusion, patient survival, cause of stent occlusion, and adverse events.
RESULTS Overall median patency of secondary stent was 112.0 days. Median stent patency of covered and uncovered SEMS was 112.0 and 181.0 days, respectively, (P = 0.373). There was a tendency towards a longer time-to-stent occlusion in uncovered SEMS group (median: 112.0 vs 181.0 days). However, it did not reach statistical significance (P = 0.214). Most common causes of occlusion were stent clogging (36.4%) and tumor ingrowth (33.3%) in covered and uncovered SEMS groups, respectively. There was no significant difference in median survival between the groups (median: 308 vs 300 days; P = 0.325). Acute cholangitis occurred in four patients (three in covered vs one in uncovered SEMS group, P = 0.607).
CONCLUSIONS In this exploratory trial, there were no statistically significant differences in stent patency, time-to-stent occlusion, patient survival, and complication rates between covered and uncovered SEMS groups. Larger confirmatory multicenter trial is needed for the clear conclusion (ClinicalTrials.gov: NCT01315522).
PubMed IF 3.5 소화기내과
2232016

제1저자 황진호, 이정표 · 교신저자 임춘수

, , , , , , , , , , , ,
Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy.
Am J Nephrol. 2016;44(6):481-492.

Abstract
BACKGROUND Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN).
METHODS Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median).
RESULTS The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients.
CONCLUSION uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.
PubMed IF 3.8 신장내과
2222016

제1저자 이선희, 박완범 · 교신저자 이신원

, , , , , , , , , , ,
Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.
Antimicrob Agents Chemother. 2016;60(11):6928-6932.

Abstract
Some proportion of type A blaZ gene-positive methicillin-susceptible Staphylococcus aureus strains exhibit the cefazolin inoculum effect (CIE). The type A blaZ gene was divided into two groups by single nucleotide polymorphisms (SNPs) at Ser226Pro and Cys229Tyr. The median cefazolin MICs at a high inoculum concentration were 5.69 μg/ml for the Ser-Cys group and 40.32 μg/ml for the Pro-Tyr group (P = 0.01). The SNPs at codons 226 and 229 in the amino acid sequence encoded by the blaZ gene were closely associated with the CIE.
PubMed IF 4.2 감염내과
2212016

제1저자 허건위 · 교신저자 진호준

, ,
The effect of sleep apnea on all-cause mortality in nondialyzed chronic kidney disease patients.
Sleep Med. 2016;27-28:32-38.

Abstract
BACKGROUND The prevalence of sleep-disordered breathing (SDB) in people with chronic kidney disease (CKD) is high. Studies on the effects of sleep apnea (SA) on treatment outcomes have been mostly focused on dialyzed CKD or renal transplant patients. Studies on the effects of SA on all-cause mortality in nondialyzed CKD patients are scarce.
METHODS We enrolled and followed up all adults who were referred for diagnostic testing for sleep apnea between March 2007 and July 2014, had undergone polysomnography, and whose records of serum creatinine levels were available. The outcomes were all-cause mortality and renal outcome.
RESULTS A total of 1454 participants were included in the study. Of these, 103 patients (7.08%) had CKD and 38 patients (2.61%) died. CKD was associated with central sleep apnea (CSA) (odds ratio [OR] = 5.158 [95% confidence interval {CI} = 1.992-13.355], p = 0.001) and severe SDB (OR = 1.737 [1.119-2.695], p = 0.014). CSA was a risk factor for all-cause mortality in nondialyzed subjects (adjusted hazard ratio [HR]= <4.250 [CI = 1.560-11.573], p = 0.005), whereas CSA was found to be a stronger risk factor for all-cause mortality in subjects with CKD (adjusted HR = 40.728 [CI = 4.765-348.117], p = 0.001). Mixed sleep apnea was related to rapid decline of renal function in nondialyzed subjects (adjusted HR = 1.932 [CI = 1.183-3.155], p = 0.009), whereas, OSA was (adjusted HR = 3.315 [CI = 1.188-9.248], p = 0.022) in CKD subjects.
CONCLUSION In nondialyzed patients, CKD was each associated with central sleep apnea (CSA) and severe SDB. CSA was an independent risk factor for all-cause mortality, and was a more evident mortality risk in CKD patients than in non-CKD participants. Rapid decline of renal function may play a role in the mortality of CKD patients associated with SA.
PubMed IF 4.1 신장내과
2202016

제1저자 변자민 · 교신저자 김인호

, , , , , , , , ,
The Impact of Methylenetetrahydrofolate Reductase C677T Polymorphism on Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation with Methotrexate Prophylaxis.
PLoS One. 2016;11(10):e0163998.

Abstract
Pharmacogenomics can explain the inter-individual differences in response to drugs, including methotrexate (MTX) used for acute graft-versus-host disease (aGVHD) prophylaxis during hematopoietic stem cell transplantation (HSCT). In real-world practice, preplanned MTX dose is arbitrarily modified according to observed toxicity which can lead to unexpected and severe aGVHD development. We aimed to validate the influence of MTHFR C677T polymorphism on the outcomes of allogenic HSCT in a relatively under-represented homogenous Asian population. A total of 177 patients were divided into 677TT group versus 677C-carriers (677CT+677CC), and clinical outcomes along with baseline characteristics were analyzed and compared. Although there was a tendency towards increased peak liver function test results and accordingly greater delta values between the highest and the baseline in 677TT group, we found no associations between genotypes and hepatotoxicity. However, the incidence of acute liver GVHD (≥ grade 2) was significantly higher in the 677TT group than in the 677CC + 677CT group (P = 0.016). A total of 25 patients (14.1%) expired due to transplantation related mortality (TRM) during the first 180 days after HSCT. Patients carrying 677TT genotype were more likely to experience early TRM than 677C-carriers. The same pattern was observed in the cumulative TRM rate, and 677TT genotype patients were more prone to cumulative TRM (P = 0.010). This translated into shorter OS for patients with 677TT compared to 677C-carriers (P = 0.010). The 3-year survival after HSCT was 29.9% for 677TT cases and 47.1% for 677C-carriers. The multivariate analysis identified 677TT genotype (HR = 1.775. 95% CI 1.122-2.808, P = 0.014) and non-CR state (HR = 2.841. 95% CI 1.627-4.960, P<0.001) as predictors for survival. In conclusion, the MTHFR 677TT genotype appears to be associated with acute liver GVHD, and represent a risk factor for TRM and survival in patients undergoing HSCT with MTX as GVHD prophylaxis.
PubMed IF 2.8 혈액종양내과
2192016

제1저자 이주명, 강지훈 · 교신저자 김효수

, , , , , , , , , , , , , ,
Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.
JACC Cardiovasc Interv. 2016;9(20):2097-2109.

Abstract
OBJECTIVES The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES).
BACKGROUND Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited.
METHODS We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM).
RESULTS A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR_adjust]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR_adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR_adjust 2.44; 95% CI: 1.54 to 3.86; HR_adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m². Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR_adjust: 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events.
CONCLUSIONS In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients.
PubMed IF 12.7 순환기내과
2182016

제1저자 최선미 · 교신저자 임재준

, , , , ,
Effect of Verbal Empathy and Touch on Anxiety Relief in Patients Undergoing Flexible Bronchoscopy: Can Empathy Reduce Patients' Anxiety?
Respiration. 2016;92(6):380-388.

Abstract
BACKGROUND Patients undergoing flexible bronchoscopy usually experience anxiety before and during the procedure.
OBJECTIVES We performed this study to investigate whether verbal empathy and intentional touch from a bronchoscopist could reduce anxiety in patients undergoing flexible bronchoscopy.
METHODS We conducted a prospective randomized trial in a university-affiliated hospital. Participants were randomly assigned to one of the following groups: a control group, a verbal empathy group, or a verbal empathy and touch group. The staff pulmonologist performing bronchoscopy expressed verbal empathy and used touch by speaking to the patient (using predefined short statements) and making eye contact, and by laying his/her left hand on the patient's right shoulder. We assessed the level of patient anxiety with a visual analog scale before and after the intervention.
RESULTS Participants were 267 patients with a median age of 65 years; 62.2% were men. Although there were no differences in changes in anxiety between the three groups, subgroup analysis of the visual analog scale including participants with higher baseline anxiety (empathy and touch group participants with anxiety ≥60 mm; empathy group and empathy and touch group participants with anxiety ≥70 mm) showed a larger reduction in anxiety than the control group.
CONCLUSIONS Verbal empathy and touch given by a bronchoscopist before bronchoscopy reduced anxiety in patients with high baseline anxiety levels.
PubMed IF 2.6 호흡기내과

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