SCI 발표논문

1. 1332014

   제1저자 김수정 · 교신저자 박종선

   Kim SJ, Lee J, Cho YJ, Park YS, Lee CH, Yoon HI, Lee SM, Yim JJ, Lee JH, Yoo CG, Lee CT, Kim YW, Han SK, Kim HB, Park JS

   Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection.

   J Infect. 2014;69(1):88-95.

   Abstract

   OBJECTIVES The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients without HIV infection (non-HIV PCP) has been increasing along with the increased use of chemotherapeutic agents and immunosuppressants, but the prognostic factors of non-HIV PCP remain unclear. This study aimed to identify the prognostic factors of non-HIV PCP.

   METHODS Immunocompromised patients without HIV infection who were diagnosed and treated for PCP were included. The PCP diagnosis was based on positive direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) results and compatible clinical symptoms and radiological findings.

   RESULTS In total, 372 non-HIV patients with positive PCP DFA or PCR findings were screened and 173 were included. Univariate analysis indicated that age, smoking, chronic lung disease or hematologic malignancy, chemotherapeutic agents, high alveolar-arterial oxygen gradient (D[A-a]O2), C-reactive protein, albumin, blood urea nitrogen (BUN), CMV antigenemia, combined bacteremia, high percentage of neutrophils and rate of co-infection in BAL fluid, and mechanical ventilator care were related to the prognosis of non-HIV PCP. Multivariate analysis revealed that high D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were indicators of a poor prognosis.

   CONCLUSIONS High D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were independent factors of poor prognosis in non-HIV PCP patients.

   PubMed IF 10 호흡기내과
2. 1322014

   제1저자 김경민 · 교신저자 신찬수

   Kim KM, Choi SH, Lim S, Moon JH, Kim JH, Kim SW, Jang HC, Shin CS

   Interactions between dietary calcium intake and bone mineral density or bone geometry in a low calcium intake population (KNHANES IV 2008-2010).

   J Clin Endocrinol Metab. 2014;99(7):2409-17.

   Abstract

   CONTEXT Little is known about the interactions between dietary calcium intake and bone strength parameters in populations or areas with low calcium intake.

   OBJECTIVE The objective of the study was to investigate the relationship between dietary calcium intake and bone mineral density (BMD) or bone geometry in an Asian population with low calcium intake.

   DESIGN AND SETTING This was a cross-sectional study of data from the Korea National Health and Nutrition Examination Survey, 2008-2010.

   PARTICIPANTS A total of 3448 men and 3812 women older than 50 years were stratified by daily dietary calcium intake: less than 400 mg/d, 400-799 mg/d, 800-1199 mg/d, and 1200 mg/d or greater.

   MAIN OUTCOME MEASURES BMD was measured by dual-energy X-ray absorptiometry and the geometric index was calculated.

   RESULTS Mean daily calcium intake was 470 mg/d in this population. BMD in the lumbar spine (both sexes) and femoral neck (women) was significantly lower only when calcium intake was less than 400 mg/d. In men, femoral neck and total hip BMD was positively related to calcium intake up to 1200 mg/d. Calcium intake less than 400 mg/d was negatively related to femoral cortical thickness and buckling ratio. These interactions disappeared when the 25-hydroxyvitamin D level was 30 ng/mL or greater in men and 20 ng/mL or greater in women.

   CONCLUSIONS Low calcium intake was significantly related with low BMD and increased risk of osteoporosis. However, the association between calcium and BMD was not consistently linear, and a sufficient vitamin D level appears to compensate for the negative influences of low calcium intake on bone.

   PubMed IF 5.4 내분비대사내과
3. 1312014

   제1저자 이상협 · 교신저자 채종일

   Lee SH, Jung BK, Park JH, Shin EH, Chai JY

   Increased intestinal epithelial cell turnover and intestinal motility in Gymnophalloides seoi-infected C57BL/6 mice.

   Korean J Parasitol. 2014;52(3):273-80.

   Abstract

   The changing patterns of goblet cell hyperplasia, intestinal epithelial cell turnover, and intestinal motility were studied in ICR and C57BL/6 mice infected with Gymnophalloides seoi (Digenea: Gymnophallidae). Whereas ICR mice retained G. seoi worms until day 7 post-infection (PI), C57BL/6 mice showed a rapid worm expulsion within day 3 PI. Immunosuppression with Depo-Medrol significantly delayed the worm expulsion in C57BL/6 mice. Goblet cell counts were increased in both strains of mice, peaking at day 1 PI in C57BL/6 mice and slowly increasing until day 7 PI in ICR mice. In C57BL/6 mice infected with G. seoi, newly proliferating intestinal epithelial cells were remarkably increased in the crypt, and the increase was the highest at day 1 PI. However, in ICR mice, newly proliferating intestinal epithelial cells increased slowly from day 1 to day 7 PI. Intestinal motility was increased in G. seoi-infected mice, and its chronological pattern was highly correlated with the worm load in both strains of mice. Meanwhile, immunosuppression of C57BL/6 mice abrogated the goblet cell proliferation, reduced the epithelial cell proliferation, and suppressed the intestinal motility. Goblet cell hyperplasia, increased intestinal epithelial cell turnover, and increased intestinal motility should be important mucosal defense mechanisms in G. seoi-infected C57BL/6 mice.

   PubMed IF 1.4 소화기내과
4. 1302014

   제1저자 정고은 · 교신저자 김윤준

   Chung GE, Lee JH, Kim YJ

   Does antiviral therapy reduce complications of cirrhosis?

   World J Gastroenterol. 2014;20(23):7306-11.

   Abstract

   Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient's serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure.

   PubMed IF 7.7 소화기내과
5. 1292014

   제1저자 김수환 · 교신저자 김지원

   Kim SH, Kim JW, Jeong JB, Lee KL, Kim BG, Choi YH

   Differential diagnosis of Crohn's disease and intestinal tuberculosis in patients with spontaneous small-bowel perforation.

   Dig Surg. 2014;31(2):151-6.

   Abstract

   BACKGROUND/AIMS Spontaneous small-bowel perforation caused by Crohn's disease (CD) or intestinal tuberculosis (ITB) is a rare disease entity. We investigated the clinical features and radiologic findings of patients with CD or ITB who presented with a spontaneous small-bowel perforation.

   METHODS Between January 2001 and December 2010, sixty-two patients underwent surgery due to a spontaneous small-bowel perforation, including 21 (33.9%) CD patients and 18 (29.0%) ITB patients. Clinical and radiologic features were compared between CD and ITB patients.

   RESULTS The mean age was significantly lower in CD patients than in ITB patients (p = 0.014). Diarrhea was more common in CD. By contrast, night sweating and a previous history of tuberculosis were more common in ITB. Only 27.8% of patients with ITB had a positive QuantiFERON-TB Gold test. CT findings such as bowel wall thickening of more than 10 mm, omental thickening, and intra-abdominal lymphadenopathy larger than 10 mm were more common among perforations caused by ITB. Mesenteric fat infiltration was a more frequent finding in CD than in ITB.

   CONCLUSIONS Clinical symptoms and radiologic findings may aid in the differential diagnosis between CD and ITB in patients presenting with spontaneous small-bowel perforation.

   PubMed IF 1.2 소화기내과
6. 1282014

   제1저자 이하정 · 교신저자 이정표

   Lee H, Hwang JH, Paik JH, Ryu HJ, Kim DK, Chin HJ, Oh YK, Joo KW, Lim CS, Kim YS, Lee JP

   Long-term prognosis of clinically early IgA nephropathy is not always favorable.

   BMC Nephrol. 2014;15:94.

   Abstract

   BACKGROUND The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival.

   METHODS We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) ≥ 60 mL/min/1.73 m2, normal blood pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome was progression to end-stage renal disease (ESRD). The secondary outcome was a 50% increase in serum creatinine level or an increase in proteinuria to >1 g/day.

   RESULTS The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110-130) mmHg, eGFR was 85.9 (74.9-100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13-0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44-24.45, P=0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20-31.79, P=0.029) were independent predictors of the secondary outcome.

   CONCLUSIONS This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients.

   PubMed IF 2.9 신장내과
7. 1272014

   제1저자 김황필 · 교신저자 김태유

   Kim HP, Han SW, Song SH, Jeong EG, Lee MY, Hwang D, Im SA, Bang YJ, Kim TY

   Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer.

   Oncogene. 2014;33(25):3334-41.

   Abstract

   Human epidermal growth factor receptor 2 (HER2)-directed treatment using trastuzumab has shown clinical benefit in HER2-positive gastric cancer. Clinical trials using lapatinib in HER2-positive gastric cancer are also currently underway. As with other molecularly targeted agents, the emergence of acquired resistance to HER2-directed treatment is an imminent therapeutic problem for HER2-positive gastric cancer. In order to investigate the mechanisms of acquired resistance to HER2-directed treatment in gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (SNU216 LR) in vitro by chronic exposure of a HER2-positive gastric cancer cell line (SNU216) to lapatinib. The resultant SNU216 LR cells were also resistant to gefitinib, cetuximab, trastuzumab, afatinib and dacomitinib. Interestingly, SNU216 LR cells displayed an epithelial-mesenchymal transition (EMT) phenotype and maintained the activation of MET, HER3, Stat3, Akt and mitogen-activated protein kinase signaling in the presence of lapatinib. Using gene expression arrays, we identified the upregulation of a variety of EMT-related genes and extracellular matrix molecules, such as Testican-1, in SNU216 LR cells. We showed that the inhibition of Testican-1 by small interfering RNA decreased Testican-1-induced, MET-dependent, downstream signaling, and restored sensitivity to lapatinib in these cells. Furthermore, treatment with XAV939 selectively inhibited β-catenin-mediated transcription and Testican-1-induced EMT signaling, leading to G1 arrest. Taken together, these data support the potential role of EMT in acquired resistance to HER2-directed treatment in HER2-positive gastric cancer, and provide insights into strategies for preventing and/or overcoming this resistance in patients.

   PubMed IF 9.1 혈액종양내과
8. 1262014

   제1저자 이은봉 · 교신저자 Pfizer

   Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, Koncz T, Krishnaswami S, Wallenstein GV, Zang C, Zwillich SH, van Vollenhoven RF, ORAL Start Investigators

   Tofacitinib versus methotrexate in rheumatoid arthritis.

   N Engl J Med. 2014;370(25):2377-86.

   Abstract

   BACKGROUND Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.

   METHODS We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).

   RESULTS Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.

   CONCLUSIONS In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.).

   PubMed IF 84.5 류마티스내과
9. 1252014

   제1저자 한승석 · 교신저자 김세중

   Han SS, Ahn SY, Ryu J, Baek SH, Chin HJ, Na KY, Chae DW, Kim S

   Proteinuria and hematuria are associated with acute kidney injury and mortality in critically ill patients: a retrospective observational study.

   BMC Nephrol. 2014;15:93.

   Abstract

   BACKGROUND Proteinuria and hematuria are both important health issues; however, the nature of the association between these findings and acute kidney injury (AKI) or mortality remains unresolved in critically ill patients.

   METHODS Proteinuria and hematuria were measured by a dipstick test and scored using a scale ranging from a negative result to 3+ in 1883 patients admitted to the intensive care unit. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The odds ratios (ORs) for AKI and 3-year mortality were calculated after adjustment for multiple covariates according to the degree of proteinuria or hematuria. For evaluating the synergistic effect on mortality among proteinuria, hematuria, and AKI, the relative excess risk due to interaction (RERI) was used.

   RESULTS Proteinuria and hematuria increased the ORs for AKI: the ORs of proteinuria were 1.66 (+/-), 1.86 (1+), 2.18 (2+), and 4.74 (3+) compared with non-proteinuria; the ORs of hematuria were 1.31 (+/-), 1.58 (1+), 2.63 (2+), and 2.52 (3+) compared with non-hematuria. The correlations between the mortality risk and proteinuria or hematuria were all significant and graded (Ptrend<0.001). There was a relative excess risk of mortality when both AKI and proteinuria or hematuria were considered together: the synergy indexes were 1.30 and 1.23 for proteinuria and hematuria, respectively.

   CONCLUSIONS Proteinuria and hematuria are associated with the risks of AKI and mortality in critically ill patients. Additionally, these findings had a synergistic effect with AKI on mortality.

   PubMed IF 2.9 신장내과
10. 1242014

    제1저자 김진현 · 교신저자 송영욱

    Kim J, Choi JY, Park SH, Yang SH, Park JA, Shin K, Lee EY, Kawachi H, Kohsaka H, Song YW

    Therapeutic effect of anti-C-X-C motif chemokine 10 (CXCL10) antibody on C protein-induced myositis mouse.

    Arthritis Res Ther. 2014;16(3):R126.

    Abstract

    INTRODUCTION C-X-C motif chemokine 10 (CXCL10) is a chemokine that plays a critical role in the infiltration of T cells in autoimmune diseases and is reported to be expressed in muscle tissue of polymyositis. To determine the therapeutic efficacy of CXCL10 blockade, we investigated the role of CXCL10 and the effect of anti-CXCL10 antibody treatment in C protein-induced myositis (CIM), an animal model of polymyositis.

    METHODS CIM was induced with human skeletal muscle C protein fragment in female C57BL/6 mice. Immunohistochemistry of CXCL10 and C-X-C motif chemokine receptor 3 (CXCR3) and measurement of serum CXCL10 were performed. Cell surface markers and interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in CIM lymph node cells was investigated by flow cytometry. Mice with CIM were treated with anti-CXCL10 antibody or control antibody (anti-RVG1) and the inflammation in muscle tissue was assessed.

    RESULTS Immunohistochemistry showed increased expression of CXCL10 and CXCR3 in the inflammatory lesions of muscle in CIM. Especially, CD8+ T cells invading myofiber expressed CXCR3. Serum level of CXCL10 was increased in CIM compared to the level in normal mice (normal mouse, 14.3 ± 5.3 pg/ml vs. CIM, 368.5 ± 135.6 pg/ml, P < 0.001). CXCR3 positivity in CD8+ T cells was increased compared to that of CD4+ T cells in the lymph node cells of CIM (CXCR3+ among CD8+ T cell, 65.9 ± 2.1% vs. CXCR3+ among CD4+ T cell, 23.5 ± 4.7%, P <0.001). Moreover, IFN-γ+ cells were increased among CXCR3+CD8+ T cells compared to CXCR3-CD8+ T cells (CXCR3+CD8+ T cell, 28.0 ± 4.2% vs. CXCR3-CD8+ T cell, 9.5 ± 1.5%, P = 0.016). Migration of lymph node cells was increased in response to CXCL10 (chemotactic index was 1.91 ± 0.45). CIM mice treated with anti-CXCL10 antibody showed a lower inflammation score in muscles than those with anti-RVG1 (median, anti-CXCL10 treatment group, 0.625 vs. anti-RVG1 treatment group, 1.25, P = 0.007).

    CONCLUSIONS CXCL10/CXCR3 expression was increased in the inflammation of CIM model and its blockade suppressed inflammation in muscle.

    PubMed IF 5.4 류마티스내과
11. 1232014

    제1저자 음영욱/박주경 · 교신저자 황진혁

    Eum YO, Park JK, Chun J, Lee SH, Ryu JK, Kim YT, Yoon YB, Yoon CJ, Han HS, Hwang JH

    Non-surgical treatment of post-surgical bile duct injury: clinical implications and outcomes.

    World J Gastroenterol. 2014;20(22):6924-31.

    Abstract

    AIM To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs).

    METHODS The study patients were enrolled from the pancreatobiliary units of a tertiary teaching hospital for the treatment of BDIs after hepatobiliary tract surgeries, excluding operations for liver transplantation and malignancies, from January 1999 to August 2010. A total of 5167 patients underwent operations, and 77 patients had BDIs following surgery. The primary end point was the treatment success rate according to different types of BDIs sustained using endoscopic or percutaneous hepatic approaches. The type of BDI was defined using one of the following diagnostic tools: endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography scan, and magnetic resonance cholangiography. Patients with a final diagnosis of BDI underwent endoscopic and/or percutaneous interventions for the treatment of bile leak and/or stricture if clinically indicated. Patient consent was obtained, and study approval was granted by the Institutional Review Board in accordance with the legal regulations of the Human Clinical Research Center at the Seoul National University Hospital in Seoul, South Korea.

    RESULTS A total of 77 patients were enrolled in the study. They were divided into three groups according to type of BDI. Among them, 55 patients (71%) underwent cholecystectomy. Thirty-six patients (47%) had bile leak only (type 1), 31 patients had biliary stricture only (type 2), and 10 patients had both bile leak and biliary stricture (type 3). Their initial treatment modalities were non-surgical. The success rate of non-surgical treatment in each group was as follows: BDI type 1: 94%; type 2: 71%; and type 3: 30%. Clinical parameters such as demographic factors, primary disease, operation method, type of operation, non-surgical treatment modalities, endoscopic procedure steps, type of BDI, time to diagnosis and treatment duration were evaluated to evaluate the prognostic factors affecting the success rate. The type of BDI was a statistically significant prognostic factor in determining the success rate of non-surgical treatment. In addition, a shorter time to diagnosis of BDI after the operation correlated significantly with higher success rates in the treatment of type 1 BDIs.

    CONCLUSION Endoscopic or percutaneous hepatic approaches can be used as an initial treatment in type 1 and 2 BDIs. However, surgical intervention is a treatment of choice in type 3 BDI.

    PubMed IF 7.7 소화기내과
12. 1222014

    제1저자 강규근 · 교신저자 이동호

    Kang KK, Lee DH, Oh DH, Yoon H, Shin CM, Park YS, Kim N, Jung HC

    Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South Korea.

    World J Gastroenterol. 2014;20(22):6932-8.

    Abstract

    AIM To investigate moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori (H. pylori) infection following failed first-line treatment.

    METHODS The sample included 312 patients for whom first-line treatment failed between January 2008 and May 2013; 27 patients were excluded, and a total of 285 patients received 7- or 14-d moxifloxacin-containing triple therapy as second-line treatment for H. pylori infection. First line regimens included 7-d standard triple (n = 172), 10-d bismuth-containing quadruple (n = 28), 14-d concomitant (n = 37), or 14-d sequential (n = 48) therapy. H. pylori status was evaluated using (13)C-urea breath testing 4 wk later, after completion of the treatment. The primary outcome was the H. pylori eradication rate analyzed using intention-to-treat (ITT) and per protocol (PP) analyses. The secondary outcome was the occurrence of serious adverse events. Demographic and clinical factors were analyzed using Student's t-tests and Pearson's χ(2) tests according to first- and second-line regimens. A P value of less than 0.05 was considered statistically significant.

    RESULTS The eradication rate of moxifloxacin-containing triple therapy was 68.4% (ITT; 95%CI: 62.8-73.5) and 73.9% (PP; 95%CI: 68.3-78.8). The eradication rate was significantly higher with 14 d compared to 7 d of treatment (77.5% vs 62.5%, P = 0.017). Peptic ulcer patients had a higher eradication rate than the patients without ulcers (82.9% vs 70.6%, P = 0.046). The demographic and clinical characteristics were not significantly different between the groups according to first-line therapies. ITT and PP analyses of the moxifloxacin-containing triple therapy indicated the following eradication rates: 70.9% (95%CI: 63.8-77.2) and 77.2% (95%CI: 70.1-83.1) for standard triple; 67.9% (95%CI: 51.5-84.2) and 67.9% (95%CI: 51.5-84.2) for bismuth-containing quadruple; 60.4% (95%CI: 46.3-73.0) and 70.7% (95%CI: 54.0-80.9) for sequential; and 67.6% (95%CI: 51.5-80.4) and 67.6%(95%CI: 51.5-80.4) for concomitant therapy. There were no statistically significant differences in the efficacy of the first-line regimens (P = 0.492). The most common adverse event was diarrhea. There were no serious adverse events and no significant differences in the frequency of side effects between the first- and second-line regimens (28.7% vs 26.1%, respectively).

    CONCLUSION Moxifloxacin-containing triple therapy as second-line treatment resulted in low eradication rates. There were no differences in the efficacy between the first-line regimens in South Korea.

    PubMed IF 7.7 소화기내과
13. 1212014

    제1저자 이정환 · 교신저자 임춘수

    Lee J, Lee JP, Park JI, Hwang JH, Jang HM, Choi JY, Kim YL, Yang CW, Kang SW, Kim NH, Kim YS, Lim CS, CRC for ESRD investigators

    Early nephrology referral reduces the economic costs among patients who start renal replacement therapy: a prospective cohort study in Korea.

    PLoS One. 2014;9(6):e99460.

    Abstract

    BACKGROUND The nature of cost-saving effects of early referral to a nephrologist in patients with chronic kidney disease (CKD) is not fully evaluated. We evaluated the health care costs before and after dialysis according to the referral time.

    METHODS A total of 879 patients who were newly diagnosed as having end-stage renal disease from August 2008 to June 2011 were prospectively enrolled. The early referral (ER) group was defined as patients who were referred to a nephrologist more than a year before dialysis and had visited a nephrology clinic 2 or more times. Patients whose referral time was less than a year were considered the late referral (LR) group. Information about medical costs was acquired from the claim data of the Korea Health Insurance Review and Assessment Service.

    RESULTS The total medical costs during the first 12 months after the initiation of dialysis were not different between the 526 ER patients and the 353 LR patients. However, the costs of the ER patients during the first month were significantly lower than those of the LR patients (ER vs. LR: 3029 ± 2219 vs. 3438 ± 2821 US dollars [USD], P = 0.025). The total 12-month health care costs before the initiation of dialysis were significantly lower in the ER group (ER vs. LR: 6206 ± 5873 vs. 8610 ± 7820 USD, P<0.001). In the multivariate analysis, ER significantly lowered the health care costs during the 12 months before (2534.0 ± 436.2 USD, P<0.001) and the first month (428.5 ± 172.3 USD, P = 0.013) after the initiation of dialysis.

    CONCLUSIONS The ER of patients with CKD to a nephrologist is associated with decreased medical costs during the pretreatment period of renal replacement therapy and the early period of dialysis initiation.

    PubMed IF 2.8 신장내과
14. 1202014

    제1저자 Jin CJ · 교신저자 임수

    Jin CJ, Yu SH, Wang XM, Woo SJ, Park HJ, Lee HC, Choi SH, Kim KM, Kim JH, Park KS, Jang HC, Lim S

    The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats.

    PLoS One. 2014;9(6):e98232.

    Abstract

    BACKGROUND Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.

    METHODS AND FINDINGS LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.

    CONCLUSIONS Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

    PubMed IF 2.8 내분비대사내과
15. 1192014

    제1저자 김경민 · 교신저자 김경민/임승길

    Kim KM, Lim SK

    Role of miRNAs in bone and their potential as therapeutic targets.

    Curr Opin Pharmacol. 2014;16:133-41.

    Abstract

    MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that regulate the expression of target genes by binding their 3'-untranslated region. miRNAs are important regulators of various biological processes, including cellular differentiation, proliferation, apoptosis, and tissue development. Furthermore, aberrant miRNA expression has emerged as an important pathomechanism in various human diseases, including osteoporosis. Thus, the therapeutic potential of miRNA has attracted great interest recently. Here, we focused on the roles of miRNAs in bone homeostasis and the potential of miRNAs as therapeutic targets.

    PubMed IF 5.5 내분비대사내과
16. 1182014

    제1저자 박진균 · 교신저자 박진균

    Park J, Lee EB, Song YW

    Decreased tumour necrosis factor-α production by monocytes of granulomatosis with polyangiitis.

    Scand J Rheumatol. 2014;43(5):403-8.

    Abstract

    OBJECTIVES We hypothesized that monocytes in patients with granulomatosis with polyangiitis (GPA) are polarized towards alternative activation with decreased tumour necrosis factor (TNF)-α production and that tissue-infiltrating monocytes/macrophages in granulomatous GPA lesions express CD163, a marker of alternative macrophage activation.

    METHOD CD16+ monocytes in peripheral blood mononuclear cells (PBMCs) were quantified by flow cytometry. Monocytes were stimulated with increasing concentrations of lipopolysaccharide (LPS), and TNF-α production was measured at 4 and 24 h. CD163 expression in lung biopsies of patients with GPA was detected by immunohistochemistry.

    RESULTS Circulating CD16+ monocytes were more frequent in GPA patients compared to controls (4.7 ± 2.8% vs. 1.9 ± 1.2%, p < 0.001). Upon activation with LPS, TNF-α production did not differ between CD16+ and CD16- monocytes. Stimulated monocytes from GPA patients produced significantly less TNF-α compared with monocytes from healthy controls (2903 ± 1320 pg/mL vs. 8335 ± 4569 pg/mL, p < 0.001). Macrophages expressing CD163 were enriched in granulomatous lung lesions of GPA patients.

    CONCLUSIONS Decreased TNF-α production by circulating monocytes and CD163 overexpression by tissue monocytes/macrophages in granulomatous pulmonary lesions may suggest that monocytes/macrophages are alternatively activated in GPA.

    PubMed IF 1.5 류마티스내과
17. 1172014

    제1저자 김민주/문민경 · 교신저자 박영주

    Kim MJ, Moon MK, Kang GH, Lee KJ, Choi SH, Lim S, Oh BC, Park DJ, Park KS, Jang HC, Park YJ

    Chronic exposure to bisphenol A can accelerate atherosclerosis in high-fat-fed apolipoprotein E knockout mice.

    Cardiovasc Toxicol. 2014;14(2):120-8.

    Abstract

    In epidemiological studies, there is growing concern regarding the association between human exposure to bisphenol A (BPA) and an increased risk for cardiovascular disease. Therefore, we investigated whether BPA accelerates atherosclerosis in mouse model. Apolipoprotein E knockout (ApoE(-/-)) mice were fed a high-fat and high-cholesterol diet with or without 50 μg/kg body weight/day BPA for 12 weeks. Atherosclerotic lesions of the aorta and aortic sinus were evaluated by Oil red O staining. After the 12-week BPA treatment, BPA significantly increased atherosclerotic lesions in the aortas of ApoE(-/-) mice by 1.7-fold (p = 0.03). Non-high-density lipoprotein (HDL) cholesterol levels in the BPA group were significantly higher compared to those in the control group (1,035 ± 70 vs. 484 ± 48 mg/dL, p = 0.02) although body weight and blood glucose levels were not different between groups. Human umbilical vein endothelial cells (HUVECs) were treated with 0.1-10 nM BPA but BPA did not affect HUVEC proliferation or migration. BPA could accelerate atherosclerosis in ApoE(-/-) mice, which may have resulted from an increase in non-HDL cholesterol levels.

    PubMed IF 3.3 내분비대사내과
18. 1162014

    제1저자 이상언 · 교신저자 오병희

    Lee SE, Cho HJ, Lee HY, Yang HM, Choi JO, Jeon ES, Kim MS, Kim JJ, Hwang KK, Chae SC, Seo SM, Baek SH, Kang SM, Oh IY, Choi DJ, Yoo BS, Ahn Y, Park HY, Cho MC, Oh BH

    A multicentre cohort study of acute heart failure syndromes in Korea: rationale, design, and interim observations of the Korean Acute Heart Failure (KorAHF) registry.

    Eur J Heart Fail. 2014;16(6):700-8.

    Abstract

    AIMS The Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea.

    METHODS AND RESULTS This is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow-up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction (LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ARBs and beta-blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In-hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in-hospital mortality. The post-discharge 30-day and 180-day all-cause mortality were 1.2% and 9.2%, respectively.

    CONCLUSIONS Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved.

    PubMed IF 10.3 순환기내과
19. 1152014

    제1저자 강영애 · 교신저자 이창훈

    Kang YA, Choi NK, Seong JM, Heo EY, Koo BK, Hwang SS, Park BJ, Yim JJ, Lee CH

    The effects of statin use on the development of tuberculosis among patients with diabetes mellitus.

    Int J Tuberc Lung Dis. 2014;18(6):717-24.

    Abstract

    OBJECTIVE To evaluate whether statin use affects the development of tuberculosis (TB) among patients with diabetes mellitus (DM).

    METHODS This is a retrospective cohort study of patients with newly diagnosed type 2 DM based on the South Korean nationwide claims database. The participants were type 2 DM patients aged 20-99 years who were newly treated with anti-diabetic drugs between 1 January 2007 and 31 December 2010. Patients who had statin prescriptions before a diagnosis of diabetes or were diagnosed with TB before diabetes were excluded.

    RESULTS Of 840,899 newly diagnosed type 2 DM patients, 281,842 (33.5%) patients were statin users and 559,057 (66.5%) were non-users. During the study period, 4075 [corrected] individuals were diagnosed with TB; the estimated incidence of TB in our cohort was 251/100,000 patient-years (95%CI 243-258). In comparison to non-TB patients, statin users were less frequent among TB patients (19.2% vs. 33.6%). After adjustment for potential baseline confounders, statin use was not associated with the development of TB in DM patients (aHR 0.98; 95%CI 0.89-1.07).

    CONCLUSIONS TB development among newly diagnosed type 2 DM was considerable, and statin use among these diabetics was not associated with a protective effect on TB incidence.

    PubMed IF 3.6 호흡기내과
20. 1142014

    제1저자 박주희 · 교신저자 유철규

    Park JH, Lee J, Park YS, Lee CH, Lee SM, Yim JJ, Kim YW, Han SK, Yoo CG

    Prognostic value of central venous oxygen saturation and blood lactate levels measured simultaneously in the same patients with severe systemic inflammatory response syndrome and severe sepsis.

    Lung. 2014;192(3):435-40.

    Abstract

    BACKGROUND Blood lactate levels and central venous oxygen saturation (ScvO(2)) are known to be useful indicators of global tissue hypoxia. However, it is unclear whether ScvO(2) correlates with lactate levels when measured simultaneously and whether changes in ScvO(2) or lactate levels in serial measurements have prognostic value. We investigated the correlation between ScvO(2) and lactate levels measured simultaneously and their association with clinical outcomes.

    METHODS We performed a prospective observational study of patients with severe systemic inflammatory response syndrome (SIRS) and severe sepsis who were admitted to the medical intensive care unit. ScvO(2) and lactate levels were measured simultaneously at the time of study enrollment, every 6 h for 24 h, and then every 24 h until the goal was reached.

    RESULTS Twenty-five patients were enrolled in the study; 13 have died and 12 have survived. There was no correlation between lactate levels and ScvO(2). Neither lactate levels nor ScvO(2) at the time of admission differed between nonsurvivors and survivors. Normalization of lactate levels within 48 h was significantly associated with survival.

    CONCLUSIONS In patients with severe SIRS and severe sepsis, simultaneously measured ScvO(2) and lactate levels showed no correlation, and normalization of lactate levels within 48 h was a predictive factor for survival.

    PubMed IF 4.3 호흡기내과
21. 1132014

    제1저자 정재우 · 교신저자 강혜련

    Jung JW, Kim JY, Yoon SS, Cho SH, Park SY, Kang HR

    HLA-DR9 and DR14 are associated with the allopurinol-induced hypersensitivity in hematologic malignancy.

    Tohoku J Exp Med. 2014;233(2):95-102.

    Abstract

    Allopurinol, a widely used urate-lowering agent, is a leading cause of severe cutaneous adverse reactions (SCARs), especially in patients with HLA-B*58:01. Despite its routine use for the prevention of tumor lysis-related hyperuricemia prior to chemotherapy, the risk of allopurinol-induced hypersensitivity has not been investigated in patients with hematologic malignancies. This retrospective cohort study was conducted to investigate the incidence and risk factors of allopurinol-induced hypersensitivity in patients at least 18 years of age with hematologic malignancies. We reviewed 463 patients who had ever taken allopurinol for the prevention of hyperuricemia prior to chemotherapy and had undergone serologic HLA typing as a pre-transplant evaluation from January 2000 to May 2010. Thirteen (2.8%) patients experienced maculopapular eruptions (MPE) and none experienced SCARs. Among subtypes of underlying hematologic malignancies, percentage of chronic myeloid leukemia was significantly higher in the allopurinol hypersensitivity group compared with the tolerant group (23.1% (3/13) vs. 5.9% (26/440), P = 0.044). According to HLA subtypes, the incidence of allopurinol-induced MPE was 4.0% in HLA-B58 (+) patients (2/50) and 2.7% in HLA-B58 (-) patients (11/403) but this difference was statistically insignificant. In contrast to HLA-B58, the frequencies of DR9 and DR14 were significantly higher in the allopurinol-induced MPE group compared with the allopurinol tolerant group (38.5% (5/13) vs. 13.6% (53/443), P = 0.019, and 38.5% (5/13) vs. 15.6% (41/440), P = 0.038, respectively). In conclusion, HLA-DR9 and DR14, but not HLA-B58, are associated with hypersensitivity reaction by allopurinol when administered in patients with hematologic malignancy prior to chemotherapy.

    PubMed IF 1.5 알레르기내과
22. 1122014

    제1저자 박진주 · 교신저자 조영석

    Park JJ, Chun EJ, Cho YS, Oh IY, Yoon CH, Suh JW, Choi SI, Youn TJ, Koo BK, Chae IH, Choi DJ

    Potential predictors of side-branch occlusion in bifurcation lesions after percutaneous coronary intervention: a coronary CT angiography study.

    Radiology. 2014;271(3):711-20.

    Abstract

    PURPOSE To identify potential predictors of side-branch occlusion after main-vessel (artery) stent implantation in bifurcation lesions by using coronary computed tomography (CT) angiography.

    MATERIALS AND METHODS This retrospective study was approved by the institutional review board; informed consent was waived. Sixty-five patients with de novo bifurcation lesions underwent coronary CT angiography before percutaneous coronary intervention. By defining side-branch occlusion as Thrombolysis in Myocardial Infarction flow grade 2 or lower, coronary CT angiography plaque characteristics associated with side-branch occlusion (ie, plaque morphology and composition) were analyzed. A multiple logistic regression analysis was undertaken to determine independent potential predictors of side-branch occlusion.

    RESULTS Of 65 patients enrolled, 12 patients (18%) had side-branch occlusion after main-vessel stent implantation. Patients with side-branch occlusion had larger mean plaque thickness in the side-branch side of the proximal main vessel (2.29 mm ± 1.87 [standard deviation] vs 1.29 mm ± 1.43, P = .043), larger plaque thickness in the noncarinal side of the side branch (1.43 mm ± 1.18 vs 0.51 mm ± 0.65, P < .001), smaller side-branch lumen diameter (1.24 mm ± 0.74 vs 1.87 mm ± 0.71, P = .007), and higher diameter stenosis (50.9% ± 24.0 vs 25.5% ± 25.3, P = .002) compared with those without side-branch occlusion. The cutoff value of proximal main vessel plaque thickness was 2.7 mm (area under the curve [AUC], 0.67; 95% confidence interval [CI]: 0.48, 0.86) and of side-branch-diameter stenosis was 40% (AUC, 0.79; 95% CI: 0.67, 0.92). Lesions with plaque thickness in proximal main vessel greater than 2.7 mm and side-branch-diameter stenosis greater than 40% were associated with a 5.6-fold and 6.2-fold, respectively, increased risk of side-branch occlusion.

    CONCLUSION Potential coronary CT angiography predictors of side-branch occlusion in bifurcation lesions are plaque thickness in the side-branch side of the proximal main vessel, plaque thickness in the noncarinal side of the side branch, side-branch lumen diameter, and side-branch-diameter stenosis. These potential predictors might guide operators planning the optimal strategy for treating bifurcation lesions.

    PubMed IF 17.6 순환기내과
23. 1112014

    제1저자 양효준 · 교신저자 이정훈

    Yang HJ, Lee JH, Lee DH, Yu SJ, Kim YJ, Yoon JH, Kim HC, Lee JM, Chung JW, Yi NJ, Lee KW, Suh KS, Lee HS

    Small single-nodule hepatocellular carcinoma: comparison of transarterial chemoembolization, radiofrequency ablation, and hepatic resection by using inverse probability weighting.

    Radiology. 2014;271(3):909-18.

    Abstract

    PURPOSE To compare the effectiveness of transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and hepatic resection (HR) in patients with small single-nodule hepatocellular carcinoma by using inverse probability weighting to control selection bias.

    MATERIALS AND METHODS This retrospective cohort study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study included 197 consecutive patients (146 men and 51 women; mean age ± standard deviation, 57.4 years ± 9.7) with single-nodule hepatocellular carcinomas measuring 3 cm or smaller and no vascular invasion who were treated initially with HR (n = 52), RFA (n = 79), or TACE (n = 66) from January 2005 to December 2006 at a single tertiary hospital. The primary endpoint was overall survival.

    RESULTS The baseline liver status of the groups differed significantly and was most favorable for the HR group, followed by the RFA group, and then the TACE group. The 5-year overall survival rates were 93.6% in the HR group, 86.6% in the RFA group, and 74.2% in the TACE group (P = .023). However, after inverse probability weighting, weighted survival rates among the three groups were similar (5-year overall survival: 85.6% with HR, 87.6% with RFA, and 80.7% with TACE; P = .834). In multivariate Cox regression analysis, TACE showed a hazard ratio of 0.978 (95% confidence interval: 0.407, 2.347; P = .960) compared with HR and of 1.335 (95% confidence interval: 0.619, 2.879; P = .461) compared with RFA.

    CONCLUSION TACE is an effective treatment that allows achievement of long-term survival rates comparable to those with HR and RFA in patients with small single-nodule hepatocellular carcinoma.

    PubMed IF 17.6 소화기내과
24. 1102014

    제1저자 오동현 · 교신저자 이동호

    Oh DH, Lee DH, Kang KK, Park YS, Shin CM, Kim N, Yoon H, Hwang JH, Jeoung SH, Kim JW, Jang ES, Jung HC

    Efficacy of hybrid therapy as first-line regimen for Helicobacter pylori infection compared with sequential therapy.

    J Gastroenterol Hepatol. 2014;29(6):1171-6.

    Abstract

    BACKGROUND AND AIM Recent prospective studies have shown that the sequential therapy has not achieved the target Helicobacter pylori eradication rate of > 80% in Korea. The aim of this study was to therefore assess the efficacy of the hybrid therapy as a first-line treatment for H. pylori eradication in a prospective trial.

    METHODS From December 2012 to August 2013, 184 patients with confirmed H. pylori infections received either the 14-day hybrid therapy or the 14-day sequential therapy. Eradication outcomes were evaluated using a 13C-urea breath test at least 4 weeks after treatment cessation.

    RESULTS A total of 184 patients (90 receiving hybrid treatment and 94 receiving sequential treatment) completed the study. The eradication rates of the hybrid and sequential therapy groups were 81.1% (73/90; 95% confidence interval [CI] = 73.0-89.2%) and 79.8% (75/94; 95%CI = 71.7-87.9%), respectively, by intention-to-treat analysis (P = 0.821). By per protocol analysis, eradication rates were 85.9% (73/85; 95%CI = 78.5-93.3%) and 82.0% (73/89; 95%CI = 74.0-89.9%; P = 0.489), respectively. There were no significant intergroup differences in treatment compliance or discontinuation induced by severe side effects.

    CONCLUSIONS The hybrid therapy achieved acceptable eradication rate (85.9%), but not statistically significantly higher rates than the sequential therapy (82.0%). Further studies are therefore needed to identify first-line treatments with even better eradication rates in the Korean population.

    PubMed IF 3.5 소화기내과
25. 1092014

    제1저자 김혜원 · 교신저자 이은영

    Kim HW, Choe HR, Lee SB, Chang WI, Chae HJ, Moon JY, Kang J, Lee S, Song YW, Lee EY

    Phenotype difference between familial and sporadic ankylosing spondylitis in Korean patients.

    J Korean Med Sci. 2014;29(6):782-7.

    Abstract

    Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6 ± 22.2 vs 35.4 ± 34.4, P=0.029) and C-reactive protein (CRP) (1.24 ± 1.7 vs 2.43 ± 3.3, P=0.003) at diagnosis, body mass index (21.9 ± 2.7 vs 23.7 ± 3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.

    PubMed IF 3.2 류마티스내과
26. 1082014

    제1저자 이주엽 · 교신저자 김나영

    Lee JY, Kim N, Kim MS, Choi YJ, Lee JW, Yoon H, Shin CM, Park YS, Lee DH, Jung HC

    Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance.

    Dig Dis Sci. 2014;59(6):1235-43.

    Abstract

    BACKGROUND Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased.

    AIMS To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade.

    METHODS We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method.

    RESULTS In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2-17.2%, P = 0.003) and clarithromycin (23.2-37.3%, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2%, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m(2), amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95% CI, 5.58-29.18; P < 0.001).

    CONCLUSIONS An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.

    PubMed IF 2.8 소화기내과
27. 1072014

    제1저자 이성준 · 교신저자 김영환

    Lee SJ, Lee J, Park YS, Lee CH, Lee SM, Yim JJ, Yoo CG, Han SK, Kim YW

    Impact of chronic obstructive pulmonary disease on the mortality of patients with non-small-cell lung cancer.

    J Thorac Oncol. 2014;9(6):812-7.

    Abstract

    INTRODUCTION The impact of chronic obstructive pulmonary disease (COPD) on the mortality of patients with lung cancer has not been studied extensively. The objective of this study is to compare the mortality and clinical characteristics of patients with non-small-cell lung cancer (NSCLC) according to the presence of COPD.

    METHODS The medical records of 221 smokers diagnosed with NSCLC were reviewed. Eligible patients were dichotomized into the COPD group (n = 111) and the non-COPD group (n = 110). The overall survival and clinical characteristics were compared, and predictors of worse survival were analyzed using Cox proportional hazards regression.

    RESULTS COPD was present in 50.2% of all patients with NSCLC, and most of the patients (92.8%) with COPD were unaware of the disease before the diagnosis of lung cancer. Patients in the COPD group were older and had a lower body mass index, higher pack-years smoking history, higher frequency of dyspnea, and higher incidence of previous malignancy. The overall survival of enrolled patients and propensity score-matched subjects was comparable between the two groups (log-rank test, p = 0.2 and 0.396, respectively). Old age, low body mass index, advanced disease stage (stages III and IV), non-squamous histology, Eastern Cooperative Oncology Group performance status of greater than or equal to 2, weight loss, and coexistence of interstitial lung disease were independent risk factors for shorter survival.

    CONCLUSION COPD frequently and subliminally coexists with NSCLC. Although differences in clinical characteristic did exist, there was no impact of COPD on the mortality of patients with NSCLC with a positive smoking history in this study.

    PubMed IF 23.3 호흡기내과
28. 1062014

    제1저자 박철기 · 교신저자 박철기/이세훈

    Park CK, Lee SH, Kim JY, Kim JE, Kim TM, Lee ST, Choi SH, Park SH, Kim IH

    Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma.

    Oncotarget. 2014;5(10):3399-407.

    Abstract

    We investigated the role of somatic mutations and a common single nucleotide polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT expression was analyzed by quantitative real time-PCR. The association between hTERT promoter genetic changes and other genomic events and clinical variables common in gliomas were examined. C228T and C250T somatic mutations were found in 60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic mutations and the SNP likely have opposing effects on hTERT expression. hTERT expression was significantly higher in the C228T or C250T mutated tumors. Tumors with the T349C genotype showed lower hTERT expression when C228T or C250T mutations were present. However, no significant survival differences were observed among the groups with or without hTERT promoter mutations and SNP. There was a significant association between genetic changes in the hTERT promoter and patient age as well as MGMT promoter methylation and EGFR amplification. hTERT expression is modulated by somatic mutations in the hTERT promoter as well as a common polymorphism. However, hTERT related genomic changes have limited value as an independent prognostic factor for clinical outcomes in glioblastomas.

    PubMed IF 6.636 혈액종양내과
29. 1052014

    제1저자 오국환,박수경 · 교신저자 안규리

    Oh KH, Park SK, Park HC, Chin HJ, Chae DW, Choi KH, Han SH, Yoo TH, Lee K, Kim YS, Chung W, Hwang YH, Kim SW, Kim YH, Kang SW, Park BJ, Lee J, Ahn C, Representing KNOW-CKD Study Group

    KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods.

    BMC Nephrol. 2014;15:80.

    Abstract

    BACKGROUND The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis).

    METHODS/DESIGN Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adults with chronic kidney disease over a 5-year period from 2011 to 2015. The participating individuals will be monitored for approximately 10 years until death or until end-stage renal disease occurs. The subjects will be classified into subgroups based on the following specific causes of chronic kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, and others. The eligible subjects will be evaluated at baseline for socio-demographic information, detailed personal/family history, office BP, quality of life, and health behaviors. After enrollment in the study, thorough assessments, including laboratory tests, cardiac evaluation and radiologic imaging, will be performed according to the standardized protocol. The biospecimen samples will be collected regularly. A renal event is defined by >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum creatinine, or end-stage renal disease. The primary composite outcome consists of renal events, cardiovascular events, and death. As of September 2013, 1,470 adult chronic kidney disease subjects were enrolled in the study, including 543 subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with hypertensive nephropathy and 249 with polycystic kidney disease.

    DISCUSSION As the first large-scale chronic kidney disease cohort study to be established and maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify the natural course, complication profiles, and risk factors of Asian populations with chronic kidney disease.

    TRIAL REGISTRATION No. NCT01630486 at http://www.clinicaltrials.gov.

    PubMed IF 2.9 신장내과
30. 1042014

    제1저자 박지영 · 교신저자 이춘택

    Park JY, Lee T, Lee H, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee JH, Lee CT

    Significance of fractional exhaled nitric oxide in chronic eosinophilic pneumonia: a retrospective cohort study.

    BMC Pulm Med. 2014;14:81.

    Abstract

    BACKGROUND Chronic eosinophilic pneumonia (CEP) is characterized by chronic eosinophilic infiltration of the lung. It is dramatically responsive to corticosteroid treatment, but symptoms and radiopacities recur frequently after tapering or discontinuing the medication. Fractional exhaled nitric oxide (FeNO) is a well-known noninvasive marker of eosinophilic airway inflammation. The aim of this retrospective cohort study was to investigate the relationships of FeNO with peripheral eosinophilia and the clinical state of CEP and its validity for predicting exacerbation of CEP.

    METHODS Standard clinical and laboratory parameters, peripheral eosinophil percentage and count, and FeNO level were measured in 18 patients with CEP at several assessment points over 1 year.

    RESULTS FeNO level was positively correlated with peripheral eosinophil count (r = 0.341, P = 0.005) and percentage (r = 0.362, P = 0.003). The median (IQR) FeNO levels were 79 (41-88) and 35 (26-49) ppb in uncontrolled (13/74 measurements) and controlled (61/74 measurements) CEP, respectively (P = 0.010). The FeNO level of 66.0 ppb showed the largest area under the curve (0.835) for predicting exacerbation of CEP (sensitivity = 0.80, specificity = 0.84).

    CONCLUSION FeNO may be useful for monitoring eosinophilic parenchymal inflammation and determining the appropriate corticosteroid dose in CEP.

    PubMed IF 3.1 호흡기내과

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