SCI 발표논문

1. 22482017

   제1저자 윤기철 · 교신저자 김나영

   Yoon K, Kim N, Kim J, Lee JW, Lee HS, Lee JC, Yoon H, Shin CM, Park YS, Ahn SH, Park DJ, Kim HH, Lee YJ, Lee KH, Kim YH, Lee DH

   Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery.

   Gut Liver. 2017;11(2):209-215.

   Abstract

   BACKGROUND/AIMS Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for "retesting" postoperative H. pylori status.

   METHODS Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively.

   RESULTS One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group.

   CONCLUSIONS A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori.

   PubMed IF 4.1 소화기내과
2. 22472017

   제1저자 최윤진, 최윤정 · 교신저자 김나영

   Choi YJ, Choi YJ, Kim N, Nam RH, Lee S, Lee HS, Lee HN, Surh YJ, Lee DH

   Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice.

   Gut Liver. 2017;11(2):243-252.

   Abstract

   BACKGROUND/AIMS The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development.

   METHODS The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting.

   RESULTS Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells.

   CONCLUSIONS Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.

   PubMed IF 4.1 소화기내과
3. 22462017

   제1저자 정광현 · 교신저자 류지곤

   Chung KH, Ryu JK, Son JH, Lee JW, Jang DK, Lee SH, Kim YT

   Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy.

   Gut Liver. 2017;11(2):298-305.

   Abstract

   BACKGROUND/AIMS Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients.

   METHODS Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m² twice daily for 14 days; oxaliplatin, 130 mg/m² on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed.

   RESULTS Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis.

   CONCLUSIONS Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.

   PubMed IF 4.1 소화기내과
4. 22452017

   제1저자 이선화 · 교신저자 이하정

   Lee S, Kang E, Yoo KD, Choi Y, Kim DK, Joo KW, Yang SH, Kim YL, Kang SW, Yang CW, Kim NH, Kim YS, Lee H

   Lower serum potassium associated with increased mortality in dialysis patients: A nationwide prospective observational cohort study in Korea.

   PLoS One. 2017;12(3):e0171842.

   Abstract

   BACKGROUND Abnormal serum potassium concentration has been suggested as a risk factor for mortality in patients undergoing dialysis patients. We investigated the impact of serum potassium levels on survival according to dialysis modality.

   METHODS A nationwide, prospective, observational cohort study for end stage renal disease patients has been ongoing in Korea since August 2008. Our analysis included patients whose records contained data regarding serum potassium levels. The relationship between serum potassium and mortality was analyzed using competing risk regression.

   RESULTS A total of 3,230 patients undergoing hemodialysis (HD, 64.3%) or peritoneal dialysis (PD, 35.7%) were included. The serum potassium level was significantly lower (P < 0.001) in PD (median, 4.5 mmol/L; interquartile range, 4.0-4.9 mmol/L) than in HD patients (median, 4.9 mmol/L; interquartile range, 4.5-5.4 mmol/L). During 4.4 ± 1.7 years of follow-up, 751 patients (23.3%) died, mainly from cardiovascular events (n = 179) and infection (n = 120). In overall, lower serum potassium level less than 4.5 mmol/L was an independent risk factor for mortality after adjusting for age, comorbidities, and nutritional status (sub-distribution hazard ratio, 1.30; 95% confidence interval 1.10-1.53; P = 0.002). HD patients showed a U-shaped survival pattern, suggesting that both lower and higher potassium levels were deleterious, although insignificant. However, in PD patients, only lower serum potassium level (<4.5 mmol/L) was an independent predictor of mortality (sub-distribution hazard ratio, 1.35; 95% confidence interval 1.00-1.80; P = 0.048).

   CONCLUSION Lower serum potassium levels (<4.5 mmol/L) occur more commonly in PD than in HD patients. It represents an independent predictor of survival in overall dialysis, especially in PD patients. Therefore, management of dialysis patients should focus especially on reducing the risk of hypokalemia, not only that of hyperkalemia.

   PubMed IF 2.8 신장내과
5. 22442017

   제1저자 유수종, 김현수 · 교신저자 윤정환, 김영수

   Yu SJ, Kim H, Min H, Sohn A, Cho YY, Yoo JJ, Lee DH, Cho EJ, Lee JH, Gim J, Park T, Kim YJ, Kim CY, Yoon JH, Kim Y

   Targeted Proteomics Predicts a Sustained Complete-Response after Transarterial Chemoembolization and Clinical Outcomes in Patients with Hepatocellular Carcinoma: A Prospective Cohort Study.

   J Proteome Res. 2017;16(3):1239-1248.

   Abstract

   This study was aimed to identify blood-based biomarkers to predict a sustained complete response (CR) after transarterial chemoembolization (TACE) using targeted proteomics. Consecutive patients with HCC who had undergone TACE were prospectively enrolled (training (n = 100) and validation set (n = 80)). Serum samples were obtained before and 6 months after TACE. Treatment responses were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). In the training set, the MRM-MS assay identified five marker candidate proteins (LRG1, APCS, BCHE, C7, and FCN3). When this five-marker panel was combined with the best-performing clinical variables (tumor number, baseline PIVKA, and baseline AFP), the resulting ensemble model had the highest area under the receiver operating curve (AUROC) value in predicting a sustained CR after TACE in the training and validation sets (0.881 and 0.813, respectively). Furthermore, the ensemble model was an independent predictor of rapid progression (hazard ratio (HR), 2.889; 95% confidence interval (CI), 1.612-5.178; P value < 0.001) and overall an unfavorable survival rate (HR, 1.985; 95% CI, 1.024-3.848; P value = 0.042) in the entire population by multivariate analysis. Targeted proteomics-based ensemble model can predict clinical outcomes after TACE. Therefore, this model can aid in determining the best candidates for TACE and the need for adjuvant therapy.

   PubMed IF 3.8 소화기내과
6. 22432017

   제1저자 신중곤 · 교신저자 김윤준

   Shin JG, Cheong HS, Lee K, Ju BG, Lee JH, Yu SJ, Yoon JH, Cheong JY, Cho SW, Park NH, Namgoong S, Kim LH, Kim YJ, Shin HD

   Identification of novel OCT4 genetic variant associated with the risk of chronic hepatitis B in a Korean population.

   Liver Int. 2017;37(3):354-361.

   Abstract

   BACKGROUND & AIMS Hepatitis B viral infection is a serious risk factor for chronic hepatitis B (CHB), cirrhosis and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) have been conducted to identify important genetic variant associated with the risk of CHB. In our previous GWAS, TCF19 was identified as one of the susceptibility genes for CHB risk (P=4.2×10^-9 at rs1419881). In order to discover possible additional causal variants around TCF19, we performed an association study by genotyping single nucleotide polymorphisms (SNPs) in OCT4, a nearby gene to TCF19.

   METHODS Nineteen OCT4 genetic variants were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 population controls).

   RESULTS Logistic regression analysis revealed that OCT4 rs1265163 showed the most significant association signal for the risk of CHB (OR=1.46, P=4.78×10^-12 ). Linkage disequilibrium and conditional analysis confirmed rs1265163 in OCT4 as a novel genetic marker for CHB susceptibility. The genetic risk scores (GRSs) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including OCT4 rs1265163, which had been identified in this study. Individuals with higher cumulative GRSs showed significantly increased ORs. The luciferase activity of rs885952, a tagging SNP of rs1265163, showed that OCT4 promoter activity was significantly different between the wild-type and SNP mutant form (P<.05).

   CONCLUSIONS This follow-up study to our previous GWAS identified a possible causal genetic variant associated with the risk of CHB, and findings from this study may prove useful in the understanding of genetic susceptibility to CHB.

   PubMed IF 6.2 소화기내과
7. 22422017

   제1저자 박경선 · 교신저자 정혜승

   Park KS, Kwak S, Cho YM, Park KS, Jang HC, Kim SY, Jung HS

   Vildagliptin reduces plasma stromal cell-derived factor-1α in patients with type 2 diabetes compared with glimepiride.

   J Diabetes Investig. 2017;8(2):218-226.

   Abstract

   AIMS/INTRODUCTION Dipeptidyl peptidase-4 inhibitors might have pleiotropic protective effects on cardiovascular disease (CVD), in contrast to sulfonylureas. Therefore, we compared various CVD risk factors between vildagliptin and glimepiride.

   MATERIALS AND METHODS We carried out a randomized, prospective and crossover trial. A total of 16 patients with type 2 diabetes whose glycated hemoglobin was >7% were randomized to add vildagliptin or glimepiride. After 12-week treatment, each drug was replaced with the other for another 12 weeks. Before and after each treatment, glucose homeostasis and CVD risk factors were assessed, and the continuous glucose monitoring system was applied to calculate glycemic variability.

   RESULTS The mean age of the participants was 60 years, 31% were men, body mass index 25.5 kg/m² and HbA1c 8.41%. Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices. Despite the improved glucose homeostasis, favorable change of CVD markers was not prominent in both the arms, along with significant weight gain. Only plasma stromal cell-derived factor (SDF)-1α decreased by 30% in the vildagliptin arm. According to regression analyses, the reduction of SDF-1α was independently associated with vildagliptin usage and serum interleukin-6 changes, but white blood cells were not related with the SDF-1α changes.

   CONCLUSION Compared with glimepiride, vildagliptin arrestingly decreased plasma SDF-1α, and its clinical implications should be further investigated.

   PubMed IF 3.6 내분비대사내과
8. 22412017

   제1저자 이서희, 김병관 · 교신저자 고성준

   Lee S, Kim BG, Kim JW, Lee KL, Koo DL, Nam H, Im JP, Kim JS, Koh SJ

   Obstructive sleep apnea is associated with an increased risk of colorectal neoplasia.

   Gastrointest Endosc. 2017;85(3):568-573.e1.

   Abstract

   BACKGROUND AND AIMS A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia.

   METHODS We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each patient with OSA, 1 or 2 controls matched for age (±5 years), sex, body mass index (BMI), and smoking who had undergone first-time screening colonoscopy were selected.

   RESULTS Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients were within the normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild: odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P = .019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P = .020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P = .002).

   CONCLUSION Physicians should be aware of the association between OSA and the development of colorectal neoplasia and explain the need for colonoscopy to patients with OSA.

   PubMed IF 8 소화기내과
9. 22402017

   제1저자 이서영 · 교신저자 강혜련

   Lee SY, Yang MS, Choi YH, Park CM, Park HW, Cho SH, Kang HR

   Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

   Ann Allergy Asthma Immunol. 2017;118(3):339-344.e1.

   Abstract

   BACKGROUND Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified.

   OBJECTIVE To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media.

   METHODS Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded.

   RESULTS Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001).

   CONCLUSION In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions.

   PubMed IF 7.1 알레르기내과
10. 22392017

    제1저자 신정훈 · 교신저자 김범석

    Shin J, Keam B, Kim M, Park YS, Kim TM, Kim DW, Kim YW, Heo DS

    Prognostic Impact of Newly Proposed M Descriptors in TNM Classification of Non-Small Cell Lung Cancer.

    J Thorac Oncol. 2017;12(3):520-528.

    Abstract

    INTRODUCTION The International Association for the Study of Lung Cancer recently proposed new M descriptors for the next edition of the TNM classification for NSCLC, subdividing the current M1b category into two subcategories: M1b, which indicates a solitary extrathoracic metastasis in a single organ, and M1c, which indicates multiple extrathoracic metastasis. The purpose of this study was to validate the prognostic value of the newly proposed M descriptors in an independent cohort with multivariate and subgroup analysis.

    METHODS A total of 1024 patients in a consecutive lung cancer database who had stage IV NSCLC treated between 2011 and 2014 were analyzed. Newly proposed M staging was used for classification and comparison of survival. Adjustment for other clinical covariates and subgroup analysis was conducted.

    RESULTS According to the newly proposed M descriptors, 262 patients (25.6%), 152 patients (14.8%), and 610 patients (59.6%) were classified into the subgroups M1a, M1b, and M1c, respectively. The median overall survival times were 22.5, 17.8, and 13.6 months for the M1a, M1b, and M1c groups, respectively (p < 0.001). After adjustment for other covariates, Cox proportional hazards regression revealed statistically significantly shorter overall survival for the M1b group than for the M1a group (hazard ratio = 1.30; 95% confidence interval: 1.03-1.65, p = 0.03) and for the M1c than the M1b group (hazard ratio = 1.57; 95% confidence interval: 1.28-1.93, p < 0.001). These differences showed a consistent tendency regardless of pathologic and molecular subtypes.

    CONCLUSIONS The newly proposed M descriptors have prognostic value in patients with stage IV NSCLC.

    PubMed IF 23.3 혈액종양내과
11. 22382017

    제1저자 김범석, 김민경 · 교신저자 박완범

    Keam B, Kim MK, Choi Y, Choi SJ, Choe PG, Lee KH, Kim TM, Kim TY, Oh DY, Kim DW, Im SA, Kim NJ, Heo DS, Park WB, Oh MD

    Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles.

    Cancer. 2017;123(5):841-848.

    Abstract

    BACKGROUND Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles.

    METHODS Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay.

    RESULTS Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040).

    CONCLUSIONS The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society.

    PubMed IF 5.6 감염내과
12. 22372017

    제1저자 이희선, 구본권 · 교신저자 김효수

    Lee H, Koo BK, Park KW, Shin ES, Lim SW, Rha SW, Bae JW, Jeon DW, Oh SK, Hur SH, Kim BS, Lee JH, Park TH, Lee NH, Kim HS, HOST-EXAM investigators

    A randomized clinical trial comparing long-term clopidogrel vs aspirin monotherapy beyond dual antiplatelet therapy after drug-eluting coronary stent implantation: Design and rationale of the Harmonizing Optimal Strategy for Treatment of coronary artery stenosis-Extended Antiplatelet Monotherapy (HOST-EXAM) trial.

    Am Heart J. 2017;185:17-25.

    Abstract

    UNLABELLED Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation.

    TRIAL DESIGN The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization.

    CONCLUSIONS The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation.

    PubMed IF 3.4 순환기내과
13. 22362017

    제1저자 안창호 · 교신저자 조영민

    Ahn CH, Kim EK, Min SH, Oh TJ, Cho YM

    Effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on lipid metabolism and endotoxemia after a high-fat meal in patients with type 2 diabetes.

    Diabetes Obes Metab. 2017;19(3):457-462.

    Abstract

    We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized, double-blind, placebo-controlled, crossover study. Ten people with type 2 diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic medications and/or lifestyle modification, were randomized to gemigliptin or placebo for 4 weeks. At the end of each treatment phase, the study participants underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue. The median (range) fasting and total area under the curve of apolipoprotein B48 (ApoB48) were significantly lower with gemigliptin than with placebo (2.9 [1.5-15.8] µg/mL vs 4.2 [1.3-23.4] µg/mL; P = .020; 35.3 [14.4-87.4] µg/mL × hour vs 42.2 [17.5-109.0] µg/mL × hour; P = .020, respectively), whereas apolipoprotein B100 showed no significant difference. Serum endotoxin levels were undetectable in 70% of the samples, so we were not able to evaluate the effect of gemigliptin on endotoxemia. The gene expression of inflammatory cytokines in subcutaneous adipose tissue was not affected by gemigliptin. Gemigliptin reduced ApoB48 levels after a high-fat meal in participants with T2DM. Whether systemic endotoxin levels can be reduced by gemigliptin requires further investigation.

    PubMed IF 6.1 내분비대사내과
14. 22352017

    제1저자 김지원, 이근욱 · 교신저자 김지현, 김태원

    Kim JW, Lee KW, Kim KP, Lee JH, Hong YS, Kim JE, Kim SY, Park SR, Nam BH, Cho SH, Chung IJ, Park YS, Oh HS, Lee MA, Kang HJ, Park YI, Song EK, Han HS, Lee KT, Shin DB, Kang JH, Zang DY, Kim JH, Kim TW

    Efficacy and Safety of FOLFIRI Regimen in Elderly Versus Nonelderly Patients with Metastatic Colorectal or Gastric Cancer.

    Oncologist. 2017;22(3):293-303.

    Abstract

    BACKGROUND Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients.

    PATIENTS AND METHODS Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy.

    RESULTS Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p = .244, and HR, 0.989; 95% CI, 0.774-1.264; p = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p = .479, and HR, 1.188; 95% CI, 0.891-1.585; p = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients.

    CONCLUSION The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status.

    PubMed IF 4.7 혈액종양내과
15. 22342017

    제1저자 김경진, 김학령 · 교신저자 조주희

    Kim KJ, Kim HL, Kim MJ, Kim CH, Lim WH, Seo JB, Chung WY, Kim SH, Kim MA, Zo JH

    Gender Difference in the Association between Aortic Pulse Pressure and Left Ventricular Filling Pressure in the Elderly: An Invasive Hemodynamic Study.

    J Card Fail. 2017;23(3):224-230.

    Abstract

    BACKGROUND This study was conducted to determine the association between aortic pulse pressure (APP) and left ventricular (LV) filling pressure in the elderly of both genders.

    METHODS A total of 211 stable elderly subjects (age ≥65 years, mean age 72.1 ± 5.2 years, 53.6% women) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease (CAD) were prospectively investigated. APP was measured in the ascending aorta using a pigtail catheter immediately before ICA. E/e', reflecting LV filling pressure, was assessed by transthoracic echocardiography.

    RESULTS There were positive linear correlations between APP and E/e' in both genders, but the correlation power was stronger in women than in men (r = 0.402, P <.001 vs r = 0.208, P = .040). The significance of this association between APP and E/e' remained after controlling for potential confounders in multiple linear regression analysis in women (β = 0.359, P <.001), but not in men (r = 0.139, P = .108).

    CONCLUSIONS Invasively measured APP is independently associated with E/e' in elderly women, but not in elderly men undergoing ICA. Aortic stiffness may be a potential mechanism for more prevalent LV diastolic dysfunction and heart failure with preserved ejection fraction in elderly women.

    PubMed IF 9.9 순환기내과
16. 22332017

    제1저자 이주명 · 교신저자 김효수

    Lee JM, Rhee TM, Hahn JY, Hwang D, Park J, Park KW, Kim HL, Kim SH, Chae IH, Doh JH, Jeon KH, Choi YJ, Park JS, Choi SH, Gwon HC, Koo BK, Alfonso F, Kim HS

    Comparison of outcomes after treatment of in-stent restenosis using newer generation drug-eluting stents versus drug-eluting balloon: Patient-level pooled analysis of Korean Multicenter in-Stent Restenosis Registry.

    Int J Cardiol. 2017;230:181-190.

    Abstract

    BACKGROUND Studies comparing the drug-eluting balloon (DEB) with contemporary drug-eluting stent (DES) in the treatment of in-stent restenosis (ISR) have been scarce. We compared that the efficacy and safety of contemporary DES versus DEB in unselected, real world patients of ISR occurred in bare-metal stent or DES.

    METHODS Patient-level pooled analysis from nationwide multicenter registries was performed with 628 consecutive patients who underwent ISR treatment using 2nd or 3rd generation DES or DEB. Target lesion failure (TLF) and patient-oriented composite outcomes (POCO, composite of all-cause mortality, all-cause myocardial infarction, or any revascularization) at 1-year follow-up were compared between the DES and DEB groups.

    RESULTS A total of 628 patients with 697 ISR lesions were treated using newer generation DES (n=409) or DEB (n=219). About 55.1% presented with acute coronary syndrome, and 15.1% showed left ventricular dysfunction. The risks of TLF and POCO were significantly lower in the DES group, even after being adjusted by an inverse probability weighted model (TLF, 9.2% vs. 17.9%, HR_adjust 0.22, 95% CI 0.11-0.47; POCO, 12.4% vs. 24.1%, HR_adjust 0.25, 95% CI 0.13-0.48, all p-values<0.001), mainly driven by the significantly lower risk of target lesion revascularization (TLR) (7.6% vs. 13.0%, HR_adjust 0.21, 95% CI 0.09-0.49, p<0.001). Treatment of ISR with DEB independently predicted TLF (HR 1.87, 95% CI 1.05-3.02, p=0.034) along with multi-vessel disease, chronic kidney disease, type B2 or C lesion, and number of treated lesion>1.

    CONCLUSIONS In unselected patients of ISR, clinical outcome at one year was mainly dependent on difference in TLR and found to be better with contemporary DES than DEB.

    PubMed IF 3.3 순환기내과
17. 22322017

    제1저자 김학령,이정표 · 교신저자 김상현

    Kim HL, Lee JP, An JN, Kim JH, Lim WH, Seo JB, Chung WY, Oh YK, Kim YS, Lim CS, Zo JH, Kim MA, Kim SH

    Soluble Tumor Necrosis Factor Receptors and Arterial Stiffness in Patients With Coronary Atherosclerosis.

    Am J Hypertens. 2017;30(3):313-318.

    Abstract

    BACKGROUND Soluble forms of tumor necrosis factor receptors (sTNFRs) are emerging target molecules of inflammatory disease. However, their role in vascular biology is not well known. This study was performed to investigate the association between serum concentrations of sTNFRs and arterial stiffness.

    METHODS A total of 117 consecutive patients with suspected coronary artery disease (CAD) (63.6 ± 11.0 years; men, 65%) who were referred for invasive coronary angiography (ICA) were prospectively enrolled. Arterial blood sTNFR1 and sTNFR2 were measured using commercially available ELISA kits. Brachial-ankle pulse wave velocity (baPWV) measurements were made within 24 hours of blood sampling for sTNFRs measurement.

    RESULTS Most of the patients (86.3%) had significant CAD (stenosis ≥ 50%) in ICA. In simple linear regression analyses, there were significant positive correlations of baPWV with sTNFR1 (r = 0.483, P < 0.001) and sTNFR2 (r = 0.366, P < 0.001). In multiple linear regression analyses, sTNFR1 (β = 0.316, P < 0.001) and sTNFR2 (β = 0.235, P = 0.005) had independent association with baPWV even after controlling for potential confounders.

    CONCLUSION sTNFR1 and sTNFR2 were independently associated with baPWV in patients undergoing ICA. This result may extend previous knowledge on close interactions between inflammation and arterial stiffening.

    PubMed IF 2.9 순환기내과
18. 22312017

    제1저자 오수연 · 교신저자 김상균

    Oh S, Kim SG, Choi JM, Jin EH, Kim JH, Im JP, Kim JS, Jung HC

    Ablation of residual gastric tumor by argon plasma coagulation after endoscopic resection.

    Surg Endosc. 2017;31(3):1093-1100.

    Abstract

    BACKGROUND For residual gastric tumors (RT) found at the treated sites after endoscopic resections (ER), additional treatment options are additional ER, surgery or argon plasma coagulation (APC). Long-term efficacy of APC as the curative modality for RT has not been fully elucidated. This study aimed to investigate the efficacy and long-term outcome of APC for RT with relevant tumor factors.

    METHODS Eighty-two patients who received ER for gastric adenocarcinoma or adenoma and were subsequently treated with APC for RT were reviewed retrospectively. Characteristics of the tumors curatively ablated with single-session of APC and the non-curatively ablated were compared by multiple logistic regression analysis. Overall rate of curative ablation and follow-up duration was calculated.

    RESULTS Initial tumor size <20 mm [odds ratio for second residual recurrence (OR) 0.16; 95 % confidence interval (CI) 0.039-0.63], en-bloc resection (OR 0.16; 95 % CI 0.039-0.72), histologic complete resection (OR 0.14; 95 % CI 0.028-0.66) and RT with flat or depressed type (OR 0.20; 95 % CI 0.051-0.77) were significantly associated with curative ablation of RT by single-session of APC. Anterior wall or lesser curvature location showed a tendency toward curative APC, but not reached statistical significance (OR 0.36; 95 % CI 0.11-1.16). A total of 60 patients (73.2 %) achieved curative ablation after single-session of APC. Eleven among the patients (n = 22) with second or more residual recurrence achieved curative ablation with one or two more additional sessions of APC. Overall rate of curative ablation was 86.6 % (71/82). From the last APC, the final curative ablation group (n = 71) has been followed up for 49.7 ± 37.4 months.

    CONCLUSIONS En-bloc resection, histologic complete resection, RT with flat or depressed type and initial tumor size less than 2 cm can be predictors of favorable clinical outcome of APC as an additional treatment for RT. For selected patients with RT, APC and close monitoring could be a reasonable alternative to immediate resection.

    PubMed IF 3.3 소화기내과
19. 22302017

    제1저자 유수종 · 교신저자 윤정환

    Yu SJ, Yoon JH, Kim W, Lee JM, Lee YB, Cho Y, Lee DH, Lee M, Yoo JJ, Cho EJ, Lee JH, Kim YJ, Kim CY

    Ultrasound-guided percutaneous portal transplantation of peripheral blood monocytes in patients with liver cirrhosis.

    Korean J Intern Med. 2017;32(2):261-268.

    Abstract

    BACKGROUND/AIMS Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients.

    METHODS A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated.

    RESULTS At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period.

    CONCLUSIONS Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients.

    PubMed IF 2.2 소화기내과
20. 22292017

    제1저자 이정실 · 교신저자 이연주

    Lee J, Cho YJ, Kim SJ, Yoon HI, Park JS, Lee CT, Lee JH, Lee YJ

    Who Dies after ICU Discharge? Retrospective Analysis of Prognostic Factors for In-Hospital Mortality of ICU Survivors.

    J Korean Med Sci. 2017;32(3):528-533.

    Abstract

    We investigated the causes of inpatient death after intensive care unit (ICU) discharge and determined predictors of in-hospital mortality in Korea. Using medical ICU registry data of Seoul National University Hospital, we performed a retrospective cohort study involving patients who were discharged alive from their first ICU admission with at least 24 hours of ICU length of stay (LOS). From January 2011 to August 2013, 723 patients were admitted to ICU and 383 patients were included. The estimated in-hospital mortality rate was 11.7% (45/383). The most common cause of death was respiratory failure (n = 25, 56%) followed by sepsis and cancer progression; the causes of hospital death and ICU admission were the same in 64% of all deaths; sudden unexpected deaths comprised about one-fifth of all deaths. In order to predict in-hospital mortality among ICU survivors, multivariate analysis identified presence of solid tumor (odds ratio [OR], 4.06; 95% confidence interval [CI], 2.01-8.2; P < 0.001), hematologic disease (OR, 4.75; 95% CI, 1.51-14.96; P = 0.013), Sequential Organ Failure Assessment (SOFA) score upon ICU admission (OR, 1.08; 95% CI, 0.99-1.17; P = 0.075), and hemoglobin (Hb) level (OR, 0.67; 95% CI, 0.52-0.86; P = 0.001) and platelet count (Plt) (OR, 0.99; 95% CI, 0.99-1.00; P = 0.033) upon ICU discharge as significant factors. In conclusion, a significant proportion of in-hospital mortality is predictable and those who die in hospital after ICU discharge tend to be severely-ill, with comorbidities of hematologic disease and solid tumor, and anemic and thrombocytopenic upon ICU discharge.

    PubMed IF 3.2 호흡기내과
21. 22282017

    제1저자 이하연 · 교신저자 박영식

    Lee HY, Lee SH, Won JK, Lee DS, Kwon NJ, Choi SM, Lee J, Lee CH, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Park YS

    Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers.

    J Korean Med Sci. 2017;32(3):415-420.

    Abstract

    Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57-73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.

    PubMed IF 3.2 호흡기내과
22. 22272017

    제1저자 강은정 · 교신저자 이하정

    Kang E, Hwang SS, Kim DK, Oh KH, Joo KW, Kim YS, Lee H

    Sex-specific Relationship of Serum Uric Acid with All-cause Mortality in Adults with Normal Kidney Function: An Observational Study.

    J Rheumatol. 2017;44(3):380-387.

    Abstract

    OBJECTIVE To explain the clinical effect of serum uric acid (SUA) levels as a risk factor for mortality, considering exclusion of kidney function.

    METHODS Participants aged over 40 years who underwent health checkups were recruited. Individuals with estimated glomerular filtrations rates < 60 ml/min/1.73 m² and who received laboratory study and colonoscopy on the same day were excluded.

    RESULTS SUA levels were higher in men than in women (5.7 ± 1.2 mg/dl for men and 4.2 ± 0.9 mg/dl for women, p < 0.001). During 12.3 ± 3.6 years of followup, 1402 deaths occurred among 27,490 participants. About 6.9% of men and 3.1% of women died. The overall mortality rate had a U-shaped association with SUA levels, a U-shaped association in men, and no association in women. There was a significant interaction of sex for the SUA-mortality association (p for interaction = 0.049); therefore, survival analysis was conducted by sex. In men, the lower SUA group had a higher mortality rate after adjustment (SUA ≤ 4.0 mg/dl, adjusted HR 1.413, 95% CI 1.158-1.724, p = 0.001) compared with the reference group (SUA 4.1-6.0 mg/dl). A higher SUA contributed to an insignificant increased mortality in men (> 8.0 mg/dl, adjusted HR 1.140, 95% CI 0.794-1.636, p = 0.479). Women failed to show any significant association between SUA and mortality.

    CONCLUSION This study provided novel evidence that SUA-mortality association differed by sex. We demonstrated that a lower SUA was an independent risk factor for all-cause mortality in men with normal kidney function.

    PubMed IF 3.7 신장내과
23. 22262017

    제1저자 김나영,박진명 · 교신저자 이상협

    Kim N, Park JM, Lee SH, Kim BH, Son JH, Ryu JK, Kim YT, Lee W

    Effect of Combinatory Treatment With Resveratrol and Guggulsterone on Mild Acute Pancreatitis in Mice.

    Pancreas. 2017;46(3):366-371.

    Abstract

    OBJECTIVES This study was conducted to assess the preventive/therapeutic effects of combined administration of resveratrol and guggulsterone on cerulein-induced acute pancreatitis in mice.

    METHODS Acute pancreatitis was induced by intraperitoneal injection of cerulein in mice. Serum amylase assay and histology were performed to measure the severity of pancreatitis. Western blotting and multiplex cytokine/chemokine analysis were conducted to understand the action mechanisms of the reagents.

    RESULTS Serum amylase assay and histology revealed that the severity of acute pancreatitis was reduced by the combinatory treatment with resveratrol and guggulsterone, but the ratio of the band intensity implied that reduced nuclear factor-κB activation is primarily responsible for the effect. The reduced amounts of keratinocyte chemoattractant (chemokine [C-X-C motif] ligand 1), interferon gamma-induced protein 10 (C-X-C motif chemokine 10) and interleukin 6 expression in the sera could be involved in attenuated immune cell migration and reduced inflammation by these reagents.

    CONCLUSIONS Combinatory treatment with resveratrol and guggulsterone marginally reduced cerulein-induced mild acute pancreatitis in mice.

    PubMed IF 2.2 소화기내과
24. 22252017

    제1저자 송경호 · 교신저자 김홍빈

    Song KH, Kim M, Kim CJ, Cho JE, Choi YJ, Park JS, Ahn S, Jang HC, Park KH, Jung SI, Yoon N, Kim DM, Hwang JH, Lee CS, Lee JH, Kwak YG, Kim ES, Park SY, Park Y, Lee KS, Lee YS, Kim HB

    Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

    Antimicrob Agents Chemother. 2017;61(3):AAC.01845-16.

    Abstract

    There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

    PubMed IF 4.2 감염내과
25. 22242017

    제1저자 강민규 · 교신저자 송우정

    Kang MG, Song WJ, Kim HJ, Won HK, Sohn KH, Kang SY, Jo EJ, Kim MH, Kim SH, Kim SH, Park HW, Chang YS, Lee BJ, Morice AH, Cho SH

    Point prevalence and epidemiological characteristics of chronic cough in the general adult population: The Korean National Health and Nutrition Examination Survey 2010-2012.

    Medicine (Baltimore). 2017;96(13):e6486.

    Abstract

    Cough is frequently self-limiting, but may persist longer in certain individuals. Most of previous studies on the epidemiology of chronic cough have only measured period prevalence, and thus have afforded limited information on the burden and natural course. We aimed to investigate the epidemiology of chronic cough by using a point prevalence measure in a large-scale general population.We analyzed cross-sectional data collected from 18,071 adults who participated in the Korean National Health and Nutrition Examination Survey 2010-2012. Presence and duration of current cough was ascertained by structured questionnaires, and cough was classified into acute (<3 weeks), subacute (3-8 weeks), or chronic cough (≥8 weeks). Demographic and clinical parameters were examined in relation to chronic cough.The point prevalences of acute, subacute, and chronic cough were 2.5 ± 0.2%, 0.8 ± 0.1% and 2.6 ± 0.2%, respectively. The proportion of current cough showed a steep decrease after 1 week of duration. However, 2 peaks in the prevalence of current cough were revealed; cough durations of less than 1 week and longer than 1 year were most common (31.1% and 27.7% of current cough, respectively). Subacute and chronic cough were more prevalent in the elderly (≥65 years); the positive associations with older age were independent of other confounders, including current smoking and comorbidities.This is the first report on the epidemiology of cough using a point prevalence measure in a nationally representative population sample. Our findings indicate a high burden of chronic cough among adults with current cough in the community. The dual-peak of cough duration suggested that the pathophysiology of acute and chronic cough may differ. The preponderance of elderly people in the prevalence of chronic cough warrants further investigation. In addition, more sophistication and validation of tools to define chronic cough will help our understanding of the epidemiology.

    PubMed IF 2 알레르기내과
26. 22232017

    제1저자 박주희 · 교신저자 정희순

    Park JH, Lee JK, Heo EY, Kim DK, Chung HS

    The effect of obesity on patients with mild chronic obstructive pulmonary disease: results from KNHANES 2010 to 2012.

    Int J Chron Obstruct Pulmon Dis. 2017;12:757-763.

    Abstract

    PURPOSE A low body mass index has been associated with high mortalities in patients with chronic obstructive pulmonary disease (COPD), and studies reveal that obesity aggravates the clinical effects of COPD. We investigated the impact of obesity on patients newly identified with COPD.

    PATIENTS AND METHODS This population-based, cross-sectional study, used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2010 to 2012. Through analyses of data from this survey, we compared concurrent comorbid diseases, symptoms, and lung functions between an obese and nonobese group of patients with COPD.

    RESULTS In total, 618 participants were diagnosed with COPD and the average forced expired volume in 1 s (FEV₁) was 79.47%±0.69%. Of the total, 30.5% of the subjects were categorized into an obese group. Subjects in the obese group were likely to have metabolic syndrome (P<0.001), hypertension (P=0.02), and a higher number of comorbidities compared to the nonobese group (2.3±0.1 vs 2.0±0.1, P=0.02). In addition, subjects in the obese group showed a lower forced vital capacity (FVC) than subjects in the nonobese group, even after adjusting for covariates (average FVC%, 89.32±1.26 vs 92.52%±0.72%, P=0.037). There were no significant differences in the adjusted FEV₁% and adjusted FEV₁/FVC between the groups.

    CONCLUSIONS Among subjects newly identified with mild COPD, participants in the obese group had more comorbid conditions and showed a lower FVC compared with subjects in the nonobese group, even after adjustment of covariates. These findings show that a combination of obesity and COPD may be a severe phenotype; therefore, early attention should be paid to obesity for the management of COPD patients.

    PubMed IF 4.1 호흡기내과
27. 22222017

    제1저자 최정연 · 교신저자 김광일

    Choi JY, Cho KJ, Kim SW, Yoon SJ, Kang MG, Kim KI, Lee YK, Koo KH, Kim CH

    Prediction of Mortality and Postoperative Complications using the Hip-Multidimensional Frailty Score in Elderly Patients with Hip Fracture.

    Sci Rep. 2017;7:42966.

    Abstract

    High mortality and dependent living after hip fracture pose a significant public health concern. Retrospective study was conducted with 481 hip fracture patients (≥65 years of age) undergoing surgery from March 2009 to May 2014. The Hip-MFS was calculated by Comprehensive Geriatric Assessment (CGA). The primary outcome was the 6-month all-cause mortality rate. The secondary outcomes were 1-year all-cause mortality, postoperative complications and prolonged hospital stay, and institutionalization. Thirty-five patients (7.3%) died within 6 months after surgery (median [interquartile range], 2.9 [1.4-3.9] months). The fully adjusted hazard ratio per 1 point increase in Hip-MFS was 1.458 (95% confidence interval [CI]: 1.210-1.758) for 6-months mortality and odds ratio were 1.239 (95% CI: 1.115-1.377), 1.156 (95% CI: 1.031-1.296) for postoperative complications and prolonged total hospital stay, respectively. High-risk patients (Hip-MFS > 8) showed higher risk of 6-month mortality (hazard ratio: 3.545, 95% CI: 1.466-8.572) than low-risk patients after adjustment. Hip-MFS successfully predict 6-month mortality, postoperative complications and prolonged hospital stay in elderly hip fracture patients after surgery. Hip-MFS more precisely predict 6-month mortality than age or existing tools (P values of comparison of ROC curve: 0.002, 0.004, and 0.044 for the ASA classification, age and NHFS, respectively).

    PubMed IF 4.9 순환기내과
28. 22212017

    제1저자 박세훈 · 교신저자 이정표

    Park S, Kim DH, Hwang JH, Kim YC, Kim JH, Lim CS, Kim YS, Yang SH, Lee JP

    Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

    PLoS One. 2017;12(2):e0172434.

    Abstract

    BACKGROUND Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary.

    METHODS We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis.

    RESULTS As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05).

    CONCLUSIONS Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

    PubMed IF 2.8 신장내과
29. 22202017

    제1저자 이지연 · 교신저자 임재준

    Lee JY, Kim DK, Lee JK, Yoon HI, Jeong I, Heo E, Park YS, Lee JH, Park SS, Lee SM, Lee CH, Lee J, Choi SM, Park JS, Joh JS, Cho YJ, Lee YJ, Kim SJ, Hwang YR, Kim H, Ki J, Choi H, Han J, Ahn H, Hahn S, Yim JJ

    Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

    Trials. 2017;18(1):68.

    Abstract

    BACKGROUND Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis.

    METHODS/DESIGN This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total).

    DISCUSSION This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future.

    TRIAL REGISTRATION ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

    PubMed IF 2.1 호흡기내과
30. 22192017

    제1저자 조재영 · 교신저자 박영식

    Cho J, Choi SM, Lee J, Lee CH, Lee SM, Kim DW, Yim JJ, Kim YT, Yoo CG, Kim YW, Han SK, Park YS

    Proportion and clinical features of never-smokers with non-small cell lung cancer.

    Chin J Cancer. 2017;36(1):20.

    Abstract

    BACKGROUND The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution.

    METHODS We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014.

    RESULTS Of the 1860 NSCLC patients, 707 (38.0%) were never-smokers. The proportions of women (83.7% vs. 5.6%) and adenocarcinoma (89.8% vs. 44.9%) were higher among never-smokers than among ever-smokers. Significantly more never-smokers were diagnosed at a younger median age (65 vs. 68 years, P < 0.001) and earlier stage (stage I-II, 44.5% vs. 38.9%, P = 0.015) compared with ever-smokers. Epidermal growth factor receptor mutations (57.8% vs. 24.4%, P < 0.001) and anaplastic lymphoma kinase rearrangements (7.8% vs. 2.8%, P < 0.001) were more common in never-smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations (5.8% vs. 9.6%, P = 0.021) were less frequently encountered in never-smokers than in ever-smokers. Never-smokers showed longer survival after adjusting for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations (hazard ratio, 0.624; 95% confidence interval, 0.460-0.848; P = 0.003).

    CONCLUSIONS More than one-third of the Korean patients with NSCLC were never-smokers. NSCLC in never-smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever-smokers.

    PubMed IF 2.814 호흡기내과

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