SCI 발표논문

2014년 253편

2232014

제1저자 정희원 · 교신저자 김광일

, , , , , ,
Frailty status can predict further lean body mass decline in older adults.
J Am Geriatr Soc. 2014;62(11):2110-7.

Abstract
OBJECTIVES To assess whether frailty is a risk factor for skeletal muscle mass decline in community-dwelling elderly people.
DESIGN Prospective observational cohort study.
SETTING Seongnam, Gyeongi Province, Korea.
PARTICIPANTS Community-dwelling Koreans aged 65 and older (n = 341).
MEASUREMENTS Bioimpedance analysis (BIA) was used to measure body composition at baseline and 5 years later. Laboratory examination and comprehensive geriatric assessment were performed at both times. Lean mass index (LMI) was defined as total body lean mass/height(2). A decrease of more than 5% in the LMI was considered to be significant. Frailty status was defined using the Cardiovascular Health Study criteria.
RESULTS LMI decline occurred in 196 (54.1%) subjects during the follow-up period (5.0 ± 0.7 years). Baseline LMI was highest in robust (17.6 ± 1.8 kg/m(2), n = 126), lower prefrail (17.0 ± 1.7 kg/m(2), n = 185), and lowest in frail (16.7 ± 1.3 kg/m(2), n = 30) subjects (P < .001). Frailty status was associated with LMI decline at 5-year follow-up (robust 0.81 ± 0.78 kg/m(2), prefrail 1.00 ± 0.92 kg/m(2), frail 1.35 ± 0.85 kg/m(2), P < .001). This effect of frailty on LMI decline persisted after adjusting for covariables (P = .02). The risk of significant LMI decline was 2.9 times as great in frail elderly adults as in those who were robust even after adjusting for covariates (95% confidence interval = 1.01-8.55).
CONCLUSION Frailty status was found to be independently associated with subsequent LMI decline in community-dwelling older adults.
PubMed IF 4.6 순환기내과
2222014

제1저자 이주명, 박종한 · 교신저자 김효수

, , , , , , , , , , , ,
Efficacy of short-term high-dose statin pretreatment in prevention of contrast-induced acute kidney injury: updated study-level meta-analysis of 13 randomized controlled trials.
PLoS One. 2014;9(11):e111397.

Abstract
BACKGROUND There have been conflicting results across the trials that evaluated prophylactic efficacy of short-term high-dose statin pre-treatment for prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG). The aim of the study was to perform an up-to-date meta-analysis regarding the efficacy of high-dose statin pre-treatment in preventing CIAKI.
METHODS AND RESULTS Randomized-controlled trials comparing high-dose statin versus low-dose statin or placebo pre-treatment for prevention of CIAKI in patients undergoing CAG were included. The primary endpoint was the incidence of CIAKI within 2-5 days after CAG. The relative risk (RR) with 95% CI was the effect measure. This analysis included 13 RCTs with 5,825 total patients; about half of them (n = 2,889) were pre-treated with high-dose statin (at least 40 mg of atorvastatin) before CAG, and the remainders (n = 2,936) pretreated with low-dose statin or placebo. In random-effects model, high-dose statin pre-treatment significantly reduced the incidence of CIAKI (RR 0.45, 95% CI 0.35-0.57, p<0.001, I(2)= 8.2%, NNT 16), compared with low-dose statin or placebo. The benefit of high-dose statin was consistent in both comparisons with low-dose statin (RR 0.47, 95% CI 0.34-0.65, p<0.001, I(2) = 28.4%, NNT 19) or placebo (RR 0.34, 95% CI 0.21-0.58, p<0.001, I(2)= 0.0%, NNT 16). In addition, high-dose statin showed significant reduction of CIAKI across various subgroups of chronic kidney disease, acute coronary syndrome, and old age (≥ 60 years), regardless of osmolality of contrast or administration of N-acetylcystein.
CONCLUSIONS High-dose statin pre-treatment significantly reduced overall incidence of CIAKI in patients undergoing CAG, and emerges as an effective prophylactic measure to prevent CIAKI.
PubMed IF 2.8 순환기내과
2212014

제1저자 김동완/오도연 · 교신저자 방영주

, , , , , , , , , , ,
A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma.
BMC Cancer. 2014;14:795.

Abstract
BACKGROUND The aim of this study was to examine the efficacy and safety of everolimus in patients with progressive unresectable adenoid cystic carcinoma (ACC).
METHODS Histologically confirmed ACC patients with documented disease progression within 12 months prior to the study entry were eligible. Everolimus was given at a dose of 10 mg daily until progression or occurrence of unacceptable toxicities. The primary endpoint was a 4-month progression-free survival (PFS).
RESULTS A total of 34 patients were enrolled. The 4-month PFS probability was 65.5% (95% one-sided confidence interval [CI], 47.7 to infinity). Median PFS duration was 11.2 months (95% CI, 3.6 to 15.8). Complete or partial response was not achieved. Twenty-seven (79.4%, 95% CI, 63.2 to 89.6) patients showed stable disease (SD). Tumor shrinkage within SD criteria was observed in 15 patients (44.1%) and SD lasting 6 months was observed in 13 patients (38.2%). Four patients had disease progression. Among the 18 patients with both pre- and post-treatment (at 8 weeks) FDG-PET scans available, 8 patients (44.4%) showed a partial metabolic response, defined as a ≥25% reduction in maximum standardized uptake values (SUVmax). The most common adverse events were stomatitis, anemia, asthenia, and leukopenia. No unexpected everolimus related toxicities were reported.
CONCLUSIONS Everolimus showed promising efficacy and good tolerability in progressive unresectable ACC.
TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT01152840.
PubMed IF 4.1 혈액종양내과
2202014

제1저자 이윤빈 · 교신저자 이정훈

, , , , , , , , , , , , , , ,
Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.
Antimicrob Agents Chemother. 2014;58(11):6710-6.

Abstract
The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.
PubMed IF 4.2 소화기내과
2192014

제1저자 김예안 · 교신저자 임수

, , , , , , , , ,
Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.
Diabetes Res Clin Pract. 2014;106(2):351-9.

Abstract
AIMS The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.
METHODS We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.
RESULTS Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects.
CONCLUSIONS In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.
PubMed IF 4.6 내분비대사내과
2182014

제1저자 이주명 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).
Am J Cardiol. 2014;114(9):1329-38.

Abstract
Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p <0.001) and off-label indication (adjusted HR 1.782, 95% CI 1.169 to 2.718, p = 0.007) were the strongest predictors of target lesion failure at 3 years. In conclusion, both stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and ZES-R. Overall incidences of target lesion failure and definite stent thrombosis, including very late stent thrombosis, were low, even in the patients with off-label indications, suggesting excellent long-term safety and sustained efficacy of both types of second-generation drug-eluting stents.
PubMed IF 2.5 순환기내과
2172014

제1저자 노성훈 · 교신저자 방영주

, , , , , , , , , , , , , , , , ,
Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial.
Lancet Oncol. 2014;15(12):1389-96.

Abstract
BACKGROUND The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial.
METHODS CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov, NCT00411229.
FINDINGS We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54-70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51-0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group. Adverse event data were not collected after the primary analysis.
INTERPRETATION Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer.
FUNDING F Hoffmann La-Roche and Sanofi.
PubMed IF 33.7 혈액종양내과
2162014

제1저자 최훈성 · 교신저자 박도준/박영주

, , , , , , , , , , , ,
Secular trends in the prognostic factors for papillary thyroid cancer.
Eur J Endocrinol. 2014;171(5):667-75.

Abstract
OBJECTIVE With the recent increasing rates of screening for thyroid cancer, the cancers now tend to be smaller and less aggressive than those that are diagnosed when presented with symptoms, suggesting changes in the clinical validity of conventional prognostic factors for outcomes. We performed the retrospective study to identify the secular trends in the prognostic factors of thyroid cancer.
METHODS We used medical records of 3147 patients diagnosed with papillary thyroid cancer (PTC) at the Seoul National University Hospital Thyroid Cancer Clinic between 1962 and 2009.
RESULTS During the median 5.1-year follow-up, the overall recurrence rate was 13.3%, and male sex, tumor size, lymph node (LN) involvement, and extrathyroidal extension (ETE) were the significant prognostic factors for recurrence. Thyroid cancer-specific mortality was 1.4%, and the associated prognostic factors were older age, male sex, and LN involvement. For tumor recurrence, the hazard ratio (HR) for male sex decreased from 2.809 (95% CI, 1.497-5.269) in the pre-1989 period to 1.142 (95% CI, 0.736-1.772) in the post-1999 period. The pathologic characteristics, such as tumor size, LN involvement, and ETE, showed similar or increasing HRs over the time periods. For cancer-specific mortality, the HR for male sex decreased from 6.460 (95% CI, 1.714-24.348) in the pre-1990 period to 0.781 (95% CI, 0.083-7.379) in the post-1999 period.
CONCLUSION The risk for poor outcomes in PTC associated with male sex decreased over time; in contrast, the risk associated with pathologic characteristics remained the same or increased over time. These trends might be associated with recent changes in the characteristics of patients with thyroid cancer.
PubMed IF 6.7 내분비대사내과
2152014

제1저자 김태혁 · 교신저자 조남한/박영주

, , , , , , , , , , , ,
Subclinical hypothyroidism in addition to common risk scores for prediction of cardiovascular disease: a 10-year community-based cohort study.
Eur J Endocrinol. 2014;171(5):649-57.

Abstract
OBJECTIVE This study was carried out to determine whether serum TSH levels improve the prediction of cardiovascular risk in addition to common clinical risk scores, given the association between subclinical hypothyroidism (SCH) and cardiovascular disease (CVD).
DESIGN We carried out an observational study in a prospective cohort.
METHODS The study included a total of 344 SCH and 2624 euthyroid participants aged over 40 years and who were without previously recorded CVDs were included in this study analysis. We measured thyroid function and traditional risk factors at baseline and estimated the 10-year cumulative incidence of CVD in a gender-stratified analysis.
RESULTS During 10 years of follow-up, 251 incident cardiovascular events were recorded. The elevation of serum TSH levels significantly increased the CV risk independent of conventional risk factors in men. In the atherosclerotic CVD (ASCVD) risk score or the Reynolds risk score (RRS) model, the addition of serum TSH levels had no effect on model discrimination as measured by the area under the curve in either women or men. Adding serum TSH did not improve the net reclassification improvement in either women (3.48% (P=0.29) in the ASCVD, -0.89% (P=0.75) in the RRS, respectively) or men (-1.12% (P=0.69), 3.45% (P=0.20), respectively) and only mildly affected the integrated discrimination Improvement in the ASCVD-adjusted model (0.30% in women and 0.42% in men, both P=0.05).
CONCLUSIONS In the context of common risk scoring models, the additional assessment of serum TSH levels provided little incremental benefit for the prediction of CV risk.
PubMed IF 6.7 내분비대사내과
2142014

제1저자 김태민 · 교신저자 허대석

, , , , , , , , , , , , , , ,
A phase II study of ifosfamide, methotrexate, etoposide, and prednisolone for previously untreated stage I/II extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial of the Korean Cancer Study Group.
Oncologist. 2014;19(11):1129-30.

Abstract
BACKGROUND Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL).
METHODS Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT).
RESULTS Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively.
CONCLUSION Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.
PubMed IF 4.7 혈액종양내과
2132014

제1저자 박세훈 · 교신저자 신동욱

, , , , , , , , ,
Low albumin-to-globulin ratio associated with cancer incidence and mortality in generally healthy adults.
Ann Oncol. 2014;25(11):2260-2266.

Abstract
BACKGROUND Chronic inflammation is known to be one of the main steps in carcinogenesis. Identification of those with chronic inflammation may help identify subjects at risk of cancer. Previous studies have reported low albumin-to-globulin ratio (AGR) to be associated with increased cancer mortality in cancer patients, but there has been no study based on healthy populations.
PATIENTS AND METHODS Our retrospective cohort study involved 26 974 generally healthy adults aged 30 or older who visited Seoul National University Hospital Health Promotion Center for self-referred health checkup. National medical service claims data were used to determine cancer incidence, and Korean death registry data was used to determine mortality. Median follow-up time for survival was 5.9 years (interquartile range 4.1 years).
RESULTS Compared with subjects with AGR ≥ 1.5, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR showed adjusted hazard ratio (aHR) 2.69 (95% confidence interval, CI, 1.54-4.72) and aHR 6.71 (95% CI 3.56-12.66) for all-cause mortality, aHR 2.95 (95% CI 1.42-6.11) and aHR 4.38 (95% CI 1.57-12.25) for cancer mortality, and aHR 2.07 (95% CI 1.28-3.36) and aHR 3.99 (95% CI 2.10-7.58) for cancer incidence, respectively. When cancer incidence events after 2 years from baseline were separately analyzed, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR were associated with aHR 1.88 (95% CI 1.01-3.48) and aHR 2.55 (95% CI 1.03-7.11) for cancer incidence, respectively. Cancer events were increased in all types of cancer, but especially in liver and hematologic malignancies.
CONCLUSIONS Low AGR is a risk factor for cancer incidence and mortality, both short- and long terms, in a generally healthy screened population. The results of this study need to be replicated in larger studies, along with the determination of the sensitivity and other diagnostic values of low AGR.
PubMed IF 80.4 소화기내과
2122014

제1저자 이민근 · 교신저자 이상협

, , , , , , , , ,
Effect of sustained use of platelet aggregation inhibitors on post-endoscopic sphincterotomy bleeding.
Dig Endosc. 2014;26(6):737-44.

Abstract
BACKGROUND AND AIM The effect of platelet aggregation inhibitors (PAI) on post-endoscopic sphincterotomy (ES) bleeding in patients who cannot discontinue PAI for sufficient time in urgent conditions has not been identified. The present study analyzed the effect of sustained use of PAI on post-procedural bleeding in patients undergoing ES.
METHODS A total of 762 patients were grouped into one of the following groups: no-PAI group (n = 601), continuation group (n = 132), and withdrawal group (n = 29). The continuation group included sustained PAI therapy (sustained user, n = 49) or those in whom therapy was interrupted <7 days prior to ES (non-sustained user, n = 83). The primary outcome was defined as the incidence, type, and severity of post-ES bleeding among groups.
RESULTS There were no significant differences between incidence, type, or severity of post-ES bleeding in the three groups. Among 132 patients with continued use of PAI, there was no significant difference regarding incidence and severity of bleeding according to sustained or non-sustained use (P = 0.071 and P = 0.086, respectively). However, post-ES delayed bleeding was more frequent in sustained PAI users than in non-sustained users (7/49, 14.3% vs 2/83, 2.4%) and was significantly associated with sustained PAI therapy in the continuation group (P = 0.013).
CONCLUSION Sustained use of PAI without interruption until ES might increase the risk of delayed bleeding.
PubMed IF 3.6 소화기내과
2112014

제1저자 진호준 · 교신저자 김광일

, , , , , , , ,
Renal function and decline in functional capacity in older adults.
Age Ageing. 2014;43(6):833-8.

Abstract
BACKGROUND longitudinal relationship between renal function, disability and mortality has not been evaluated.
OBJECTIVE we investigated the temporal association between renal function and disability, and aimed to identify the influence of disability on mortality according to renal function in a cohort of older Koreans.
DESIGN/SETTING Korean Longitudinal Study on Health and Aging is a prospective, population-based cohort.
SUBJECTS community-dwelling Koreans ≥65 years of age.
MAIN OUTCOME MEASURES Korean version of activities of daily living (ADL), Instrumental activities of daily living (IADL) and all-cause mortality.
RESULTS a total of 984 participants were followed for 5 years with a 70.9% participation rate. The participants were categorized into three groups according to their baseline estimated glomerular filtration rates (eGFRs) (Group I, ≥60; Group II, 45-59; and Group III, <45 ml/min/1.73 m(2)). Baseline eGFR was higher in participants who maintained functional status compared with participants who died or had disability at follow-up examination. The incidence of ADL/IADL decline was 13, 12.5 and 29.5% in participants who showed improvement, no change, and decline in renal function, respectively (P = 0.01). The hazard ratio for mortality in the subgroup with IADL disability was 1.87 (95% CI: 1.10-3.20, P = 0.022) in Group I, and 2.53 (95% CI: 1.57-4.09, P<0.001) in Groups II and III after adjustment.
CONCLUSIONS impaired renal function was related to disability and ADL/IADL decline. The effect of ADL/IADL disability on mortality was more prominent in participants with impaired eGFR.
PubMed IF 7.4 순환기내과
2102014

제1저자 김유정 · 교신저자 이근욱

, , , , , , ,
Gastric cancer with initial bone metastasis: a distinct group of diseases with poor prognosis.
Eur J Cancer. 2014;50(16):2810-21.

Abstract
BACKGROUND Bone metastasis (BM) is reported as a poor prognostic factor in gastric cancer. However, the clinicopathologic characteristics and clinical outcomes of patients with BM compared with patients without BM have not been well described.
PATIENTS AND METHODS The medical records of all metastatic or recurrent gastric cancer (MRGC) patients who visited our institution were reviewed. A total of 137 evaluable patients with BM were analysed together with historical control without BM (N=111).
RESULTS Of 1342 MRGC patients, 141 (10.5%) had BM. Patients with BM could be divided into initial BM (BM present at initial diagnosis of MRGC; N=90) and late BM (N=47) groups. The median survival after the diagnosis of BM in all patients was 4.4 months (95% confidence interval [CI] 3.69-5.11). However, overall survival after the diagnosis of MRGC was significantly shorter in the initial BM group (5.0 versus 12.2 months, p<0.001). Compared with historical controls, patients with initial BM showed distinct clinicopathologic characteristics. Independent predictors of initial BM were a younger age, signet ring cell histology, primary tumour involving ⩾two-thirds of the stomach, pleural metastasis, thrombocytopenia and elevated alkaline phosphatase. According to a Cox proportional hazard model including both patients with BM and historical controls, initial BM, poor performance status, peritoneal metastasis, hypercalcemia and high carcinoembryonic antigen (CEA) were identified as poor prognostic factors, whereas chemotherapy was identified as a favourable factor (hazard ratio [HR] 0.33, 95% CI 0.22-0.49).
CONCLUSION MRGC with initial BM is a distinct group of diseases with specific clinicopathologic characteristics and poor prognosis. Chemotherapy may improve survival in these patients.
PubMed IF 7.9 혈액종양내과
2092014

제1저자 박종선 · 교신저자 김영환

, , , , , , ,
Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.
BMC Pulm Med. 2014;14:168.

Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.
METHODS The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.
RESULTS The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.
CONCLUSIONS The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.
PubMed IF 3.1 호흡기내과
2082014

제1저자 이효정 · 교신저자 김나영

, , , , , , , , ,
Association between halitosis diagnosed by a questionnaire and halimeter and symptoms of gastroesophageal reflux disease.
J Neurogastroenterol Motil. 2014;20(4):483-90.

Abstract
BACKGROUND/AIMS The relationship between halitosis and gastroesophageal reflux disease (GERD) remains controversial. The aim of this study was to investigate an association between subjective and objective halitosis and GERD.
METHODS The subjects were enrolled from participants who visited a health promotion center at Seoul National University Bundang Hospital. For diagnosis of halitosis, a questionnaire was requested, and volatile sulfur compounds (VSCs) were measured by Halimeter. Self-conscious halitosis was defined as halitosis perceived by himself or herself. Informed halitosis was defined as hal-itosis perceived by others. Objective halitosis was defined when mean VSCs values were > 100 parts per billion. GERD was defined based on a questionnaire and endoscopy, including erosive esophagitis and non-erosive reflux disease (NERD).
RESULTS A total of 54 subjects (male:female = 33:21) with mean age of 46.0 ± 11.4 years were analyzed. The mean VSCs values were not significantly different between presence and absence of self-conscious halitosis (P = 0.322), but significantly different be-tween presence and absence of informed halitosis (P = 0.021). Informed halitosis was associated with objective halitosis (P = 0.039). GERD, erosive esophagitis and NERD did not correlate with objective halitosis (P = 0.556, 0.206 and 0.902, re-spectively). In multivariable analysis, the relationship between objective halitosis and GERD symptoms including chest pain, heart burn, acid regurgitation, epigastric pain, hoarseness, globus sensation and coughing was not significant. Besides, GERD was not associated with self-conscious halitosis, informed halitosis and objective halitosis, respectively.
CONCLUSIONS GERD might not be associated with self-conscious, informed halitosis and objective halitosis indicated by Halimeter results. Informed halitosis could be correlated with objective halitosis determined by the Halimeter.(J Neurogastroenterol Motil 2014;20:483-490).
PubMed IF 3.7 소화기내과
2072014

제1저자 고성준, 김민구 · 교신저자 김병관

, , , , ,
Psychosocial stress in nurses with shift work schedule is associated with functional gastrointestinal disorders.
J Neurogastroenterol Motil. 2014;20(4):516-22.

Abstract
BACKGROUND/AIMS The aim of this study was to investigate the role of psychosocial problems and their associations with rotating shift work in the development of functional gastrointestinal disorders.
METHODS In this cross-sectional observation study, survey was administered to nurses and nurse assistants in a referral hospital. In addi-tion to demographic questions, subjects were asked to complete the Rome III Questionnaire, Pittsburgh Sleep Quality Index and Rome III Psychosocial Alarm Questionnaire.
RESULTS Responses from 301 subjects were assessed. The overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 15.0% and 19.6%, respectively. Psychosocial alarms were prevalent in the nursing personnel (74.8% with alarm pres-ence and 23.3% with serious condition) and were more frequent among rotating shift workers (84.7% vs. 74.5% for alarm presence and 28.1% vs. 13.3% for serious condition). The prevalence of both IBS and FD significantly increased with psychoso-cial risk. An independent risk factor for IBS was serious psychosocial alarm (adjusted odds ratio [aOR], 10.75; 95% confidence interval (CI), 1.30-88.99; P = 0.028). Serious psychosocial alarm was an independent risk factor for FD (aOR, 7.84; 95% CI, 1.98-31.02; P = 0.003). Marriage (aOR 0.30; 95% CI, 0.09-0.93; P = 0.037) was associated with the decreased risk of FD.
CONCLUSIONS The high prevalence of psychosocial stress among nurses who work rotating shifts is associated with the development of func-tional gastrointestinal disorders.(J Neurogastroenterol Motil 2014;20:516-522).
PubMed IF 3.7 소화기내과
2062014

제1저자 임수 · 교신저자 Meigs JB

, , , , , , , ,
Electronic medical record cancer incidence over six years comparing new users of glargine with new users of NPH insulin.
PLoS One. 2014;9(10):e109433.

Abstract
BACKGROUND Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years.
METHODS AND FINDINGS From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36-1.19).
CONCLUSIONS Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.
PubMed IF 2.8 내분비대사내과
2052014

제1저자 강지훈, 윤지연, 허진 · 교신저자 김효수

, , , , , , , , , ,
Erythropoietin priming improves the vasculogenic potential of G-CSF mobilized human peripheral blood mononuclear cells.
Cardiovasc Res. 2014;104(1):171-82.

Abstract
AIMS From our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ((mob)PBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming (mob)PBMCs with erythropoietin (EPO) to augment its therapeutic efficacy.
METHODS AND RESULTS (mob)PBMCs were obtained from healthy volunteers after a 3-day subcutaneous injection of G-CSF (10 μg/kg). About 40% of (mob)PBMCs were EPO receptor (EPOR) (+) and responded to 6 h EPO-priming (10 IU/mL) by increasing the expression of vasculogenic factors (i.e. IL8, IL10, bFGF, PDGF, MMP9) and adhesion molecules (i.e. integrin αV, β1, β2, β8) through the JAK2 and Akt pathway. These responses were also observed in PBMCs from elderly patients with coronary disease. The conditioned media from EPO-primed (mob)PBMCs contained various cytokines such as IL8, IL10, TNFα, and PDGF, which enhanced the migration and tube formation capability of endothelial cells. EPO-primed (mob)PBMCs also showed increased adhesion on endothelial cells or fibronectin. Augmented vasculogenic potential of EPO-primed (mob)PBMCs was confirmed in a Matrigel plug assay, ischaemic hindlimb, and myocardial infarction models of athymic nude mice. There were two action mechanisms: (i) cellular effects confirmed by direct incorporation of human (mob)PBSCs into mouse vasculature and (ii) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed (mob)PBMCs.
CONCLUSION Brief ex vivo EPO-priming is a novel method to augment the vasculogenic potential of human (mob)PBMCs, which would help to achieve better results after intracoronary infusion in myocardial infarction patients.
PubMed IF 12.5 순환기내과
2042014

제1저자 김계형 · 교신저자 오명돈

, , , , , , , ,
Human granulocytic anaplasmosis, South Korea, 2013.
Emerg Infect Dis. 2014;20(10):1708-11.

Abstract
We report a patient with human granulocytic anaplasmosis in South Korea. The patient had fever and thrombocytopenia. Human granulocytic anaplasmosis was confirmed by seroconversion, PCR, and sequence analysis for Anaplasma phagocytophilum. Morulae were observed in the cultured HL-60 cells inoculated with blood from the patient.
PubMed IF 7.9 감염내과
2032014

제1저자 황성욱 · 교신저자 김나영

, , , , , , , ,
Association of SLC6A4 5-HTTLPR and TRPV1 945G>C with functional dyspepsia in Korea.
J Gastroenterol Hepatol. 2014;29(10):1770-7.

Abstract
BACKGROUND AND AIM The association of various genetic polymorphisms with functional dyspepsia (FD) has been suggested, but the results were still controversial. The aim of the present study was to assess the association of GNB3 825C>T, SLC6A4 5-HTTLPR, ADRA2A-1291C>G, CCK-1R intron 779T>C, and TRPV1 945G>C polymorphisms with FD based on Rome III criteria in Korea.
METHODS Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between 2009 and 2012. One hundred and twelve FD patients and 269 controls were enrolled.
RESULTS In SLC6A4 5-HTTLPR polymorphism, the frequency of S/S genotype was significantly lower than that of L/L + L/S genotype in FD compared to controls (P < 0.05). After stratification according to Helicobacter pylori infection, the S/S genotype was significantly associated with H. pylori-positive epigastric pain syndrome (EPS) patients (adjusted odds ratio (OR) 0.46; 95% confidence interval (CI) 0.22-0.99; P = 0.048). In TRPV1 945G>C polymorphism, the frequency of C/C genotype was lower in FD compared to controls (P = 0.057). The C carrier and C/C genotype was significantly associated with postprandial distress syndrome (PDS) and EPS, respectively (adjusted OR 0.47 and 0.43; 95% CI 0.25-0.90 and 0.20-0.93; P = 0.021 and 0.033). After stratification, the significant associations remained in H. pylori-positive PDS and EPS patients (adjusted OR 0.37 and 0.28; 95% CI 0.16-0.88 and 0.09-0.85; P = 0.024 and 0.025).
CONCLUSIONS The genetic polymorphism of SLC6A4 5-HTTLPR and TRPV1 945G>C could be one of the pathophysiological factors of FD, especially in the case of H. pylori-positive patients in Korea.
PubMed IF 3.5 소화기내과
2022014

제1저자 김범석 · 교신저자 김동완

, , , , , , ,
Nomogram Predicting Clinical Outcomes in Non-small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
Cancer Res Treat. 2014;46(4):323-30.

Abstract
PURPOSE The aim of this study was to develop a pragmatic nomogram for prediction of progressionfree survival (PFS) for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in EGFR mutant non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS A total of 306 recurred or metastatic NSCLC patients with EGFR mutation, who received EGFR TKIs, were enrolled in this study. We developed the nomogram, using a Cox proportional hazard regression model for PFS.
RESULTS The median PFS was 11.2 months. Response rate to EGFR TKI was 71.9%. Multivariate Cox model identified disease status, performance status, chemotherapy line, response to EGFR TKI, and bone metastasis as independent prognostic factors, and the nomogram for PFS was developed, based on these covariates. The concordance index for a nomogram was 0.708, and the calibration was also good.
CONCLUSION We developed a nomogram, based on clinical characteristics, for prediction of the PFS to EGFR TKI in NSCLC patients with EGFR mutation.
PubMed IF 4.2 혈액종양내과
2012014

제1저자 정고은 · 교신저자 임선희

, , , , , , , ,
Factors that determine prolonged cecal intubation time during colonoscopy: impact of visceral adipose tissue.
Scand J Gastroenterol. 2014;49(10):1261-7.

Abstract
OBJECTIVE Various factors including age, sex, body mass index (BMI) and history of operation have been linked to the colonoscopic intubation time. The aims of this study were to identify the factors predicting cecal intubation time (CIT) and to evaluate the effect of the visceral adipose tissue (VAT) area on CIT.
MATERIAL AND METHODS A total of 1386 consecutive subjects who underwent colonoscopy and abdominal CT on the same day for a health checkup at a single health care center in Korea from August to December 2011 were studied prospectively. Age, sex, BMI, height, waist circumference, history of operation, symptoms of irritable bowel syndrome, bowel preparation status, experience of colonoscopists, VAT amount on abdominal CT and time required to reach the cecum were analyzed.
RESULTS The mean age of the subjects was 53.0 ± 9.6 years, and 63.5% were male. The median CIT was 271 s. Univariate analyses showed that female gender, old age, shorter height, lower BMI, prior history of surgery and lower VAT were associated with longer CIT. To adjust for confounding effects of the gender, we investigated the genders separately in multivariate analysis. Older age and lower VAT were associated with prolonged CIT. However, the significance of association of VAT on prolonged CIT disappeared in women.
CONCLUSION This study demonstrates that CIT is prolonged by lower VAT area in men. This is the first study to demonstrate a direct association between VAT area and CIT.
PubMed IF 1.8 소화기내과
2002014

제1저자 임수 · 교신저자 장학철

, , , , , , , , ,
Differences in pancreatic volume, fat content, and fat density measured by multidetector-row computed tomography according to the duration of diabetes.
Acta Diabetol. 2014;51(5):739-48.

Abstract
Pancreatic volume and fat content might be associated with β-cell function or insulin resistance (IR). We investigated the difference in pancreatic volume and fat content between age- and body mass index (BMI)-matched normal subjects and patients with having different durations of type 2 diabetes (T2D). We compared pancreatic volume and fat parameters between 50 age- and BMI-matched normal subjects, 51 subjects with newly diagnosed type 2 diabetes (T2D-new), 53 subjects with T2D <5 years (T2D<5Y), and 52 subjects with T2D ≥5 years (T2D≥5Y). Age and BMI were matched to range of ±2 years and ±0.5 kg/m(2), respectively. Pancreatic volume and fat were measured by multidetector-row computed tomography with 64 detector-row scanner. The difference in Hounsfield units between pancreas and spleen (HUp-s) was investigated for fat density. Anthropometric and biochemical parameters including the homeostasis model assessment of IR (HOMA-IR) and the insulinogenic index (IGI) were measured. Compared with normal subjects, patients with T2D had significantly smaller pancreatic volume, greater pancreatic fat, and lower HUp-s. Among the groups with T2D, pancreatic volume decreased and pancreatic fat percentage and HUp-s increased from the T2D-new to the T2D<5Y and T2D>5Y groups. Pancreatic volume and fat and HUp-s values were associated with HbA1c and triglyceride levels. Pancreatic volume was correlated with IGI while pancreatic fat and HUp-s values were correlated with HOMA-IR. The current study suggests that pancreatic volume and fat deposition might be associated with the development and progression of T2D in Korean subjects.
PubMed IF 3.1 내분비대사내과
1992014

제1저자 김정희, 임수 · 교신저자 장학철

, , , , , , , ,
Sarcopenia: an independent predictor of mortality in community-dwelling older Korean men.
J Gerontol A Biol Sci Med Sci. 2014;69(10):1244-52.

Abstract
BACKGROUND The concept of sarcopenia has expanded recently to include muscle strength or physical performance. We investigated whether the Europe Working Group on Sarcopenia in Older People (EWGSOP) definition of sarcopenia predicts the risk of all-cause mortality in community-dwelling older adults.
METHODS This study included 284 men and 272 women aged 65 and older. The outcome was all-cause mortality during the 6-year follow-up period. We defined sarcopenia based on the EWGSOP definitions of sarcopenia: height (ht)- or weight (wt)-adjusted appendicular skeletal muscle mass (ASM/ht(2) or ASM/wt) assessed by dual-energy x-ray absorptiometry, leg muscle strength, and short physical performance battery test score.
RESULTS During the 6-year follow-up, 40 men and 19 women died. The risk of death was 2.99 times and 3.22 times higher in men with sarcopenia identified by ASM/ht(2) and ASM/wt, respectively, compared with nonsarcopenic men. The hazard ratio for death was 5.37 for men with weak leg muscle strength. Men with a low short physical performance battery score had a 3.15 times higher risk of death compared with those with high short physical performance battery scores, even after adjusting for all covariates. The adjusted hazard ratios for EWGSOP-defined sarcopenia were 4.00 for ASM/ht(2) and 6.89 for ASM/wt in men. By contrast, sarcopenia defined by these criteria was not associated with a higher risk of death in women.
CONCLUSIONS Our data suggest that, in older men, EWGSOP-defined sarcopenia is related to higher mortality compared with nonsarcopenia regardless of the ASM/ht(2) or ASM/wt index. In older women, further studies with large sample sizes are needed to assess whether EWGSOP-defined sarcopenia increases the mortality risk.
PubMed IF 4.6 내분비대사내과
1982014

제1저자 강지훈, 허진, 강진아 · 교신저자 김효수

, , , , , , , , , ,
Activated platelet supernatant can augment the angiogenic potential of human peripheral blood stem cells mobilized from bone marrow by G-CSF.
J Mol Cell Cardiol. 2014;75:64-75.

Abstract
Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous 'activated platelet supernatant (APS)' as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells ((mob)PBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor. APS was collected separately from the platelet rich plasma after activation by thrombin. (mob)PBSCs were primed for 6h before analysis. Compared to naive platelet supernatants, APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF. APS-priming for 6h induced (mob)PBSCs to express key angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrins α5, β1 and β2). Also (mob)PBSCs were polarized toward CD14(++)/CD16(+) pro-angiogenic monocytes. The priming effect was reproduced by an in vitro reconstruction of APS. Through this phenotype, APS-priming increased cell-cell adhesion and cell-extracellular matrix adhesion. The culture supernatant of APS-primed (mob)PBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of human umbilical vein endothelial cells. In vivo transplantation of APS-primed (mob)PBSCs into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In safety analysis, platelet activity increased after mixing with (mob)PBSCs regardless of priming, which was normalized by aspirin treatment. Collectively, our data identify that APS-priming can enhance the angiogenic potential of (mob)PBSCs, which can be used as an adjunctive strategy to improve the efficacy of cell therapy for ischemic diseases.
PubMed IF 4.9 순환기내과
1972014

제1저자 문재훈 · 교신저자 김기웅, 장학철

, , , , , , , , , ,
The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma.
J Clin Endocrinol Metab. 2014;99(10):3782-9.

Abstract
CONTEXT Several studies have evidenced the association between subclinical hyperthyroidism and cognitive impairment in the elderly. However, the effect of long-term TSH suppressive therapy on the cognitive function in elderly patients with differentiated thyroid carcinoma (DTC) is still unclear.
OBJECTIVE Our aim was to investigate the effect of long-term TSH suppression on the cognitive function of elderly patients with DTC.
DESIGN, SETTING, AND PARTICIPANTS A cross-sectional case-control study including 50 DTC patients aged 65 years or older (mean age 70.9 ± 5.0 y) who have received a TSH-suppressive therapy for at least 5 years and 90 control subjects matched for age, sex, education period, and depressive mood was conducted. Major Outcome Measure: Comprehensive cognitive domains were compared between the patient and control groups. The association between serum thyroid hormone concentration and cognitive function was investigated.
RESULTS The patient group had higher serum free T4 levels and suppressed TSH levels compared with the control group. Age, sex, education period, the Korean version of the Geriatric Depression Scale scores, and Cumulative Illness Rating Scale scores were not different between the 2 groups. All assessed neuropsychiatric tests were comparable in both groups. In the patient group, those with higher serum free T4 levels performed better on Mini-Mental State Examination and Trail Making Test A. The association between serum free T4 and Trail Making Test A was maintained after adjusting for age, education period, the Korean version of the Geriatric Depression Scale, and Cumulative Illness Rating Scale. In the control group, serum free T4 and TSH levels were not associated with any of the assessed cognitive domains.
CONCLUSION Our results demonstrated the safety of long-term TSH suppression on the cognitive function in elderly DTC patients. Furthermore, the positive correlations between serum free T4 levels and some cognitive domains suggest the potential beneficial effects of exogenous levothyroxine on the cognitive function of patients who lack endogenous thyroid hormone.
PubMed IF 5.4 내분비대사내과
1962014

제1저자 한정규 · 교신저자 김효수

, , , , , , , , , , , , , ,
Direct conversion of adult skin fibroblasts to endothelial cells by defined factors.
Circulation. 2014;130(14):1168-78.

Abstract
BACKGROUND Cell-based therapies to augment endothelial cells (ECs) hold great therapeutic promise. Here, we report a novel approach to generate functional ECs directly from adult fibroblasts.
METHODS AND RESULTS Eleven candidate genes that are key regulators of endothelial development were selected. Green fluorescent protein (GFP)-negative skin fibroblasts were prepared from Tie2-GFP mice and infected with lentiviruses allowing simultaneous overexpression of all 11 factors. Tie2-GFP(+) cells (0.9%), representing Tie2 gene activation, were detected by flow cytometry. Serial stepwise screening revealed 5 key factors (Foxo1, Er71, Klf2, Tal1, and Lmo2) that were required for efficient reprogramming of skin fibroblasts into Tie2-GFP(+) cells (4%). This reprogramming strategy did not involve pluripotency induction because neither Oct4 nor Nanog was expressed after 5 key factor transduction. Tie2-GFP(+) cells were isolated using fluorescence-activated cell sorting and designated as induced ECs (iECs). iECs exhibited endothelium-like cobblestone morphology and expressed EC molecular markers. iECs possessed endothelial functions such as Bandeiraea simplicifolia-1 lectin binding, acetylated low-density lipoprotein uptake, capillary formation on Matrigel, and nitric oxide production. The epigenetic profile of iECs was similar to that of authentic ECs because the promoters of VE-cadherin and Tie2 genes were demethylated. mRNA profiling showed clustering of iECs with authentic ECs and highly enriched endothelial genes in iECs. In a murine model of hind-limb ischemia, iEC implantation increased capillary density and enhanced limb perfusion, demonstrating the in vivo viability and functionality of iECs.
CONCLUSIONS We demonstrated the first direct conversion of adult fibroblasts to functional ECs. These results suggest a novel therapeutic modality for cell therapy in ischemic vascular disease.
PubMed IF 41.3 순환기내과
1952014

제1저자 허건위 · 교신저자 진호준

, , , , , , ,
Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy.
J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S155-63.

Abstract
We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-β1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRα, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRα and SREBP-1 expression and oxidative stress.
PubMed IF 3.2 신장내과
1942014

제1저자 김성균 · 교신저자 진호준

, , , , , ,
Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content.
J Korean Med Sci. 2014;29 Suppl 2(Suppl 2):S146-54.

Abstract
The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 µM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.
PubMed IF 3.2 신장내과

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