SCI 발표논문

2016년 247편

972016

제1저자 김수환, 김병관 · 교신저자 김원

, , , , , , , ,
Characterization of gastrointestinal hemorrhage and prediction of mortality in Asian patients with alcoholic hepatitis.
J Gastroenterol Hepatol. 2016;31(4):814-21.

Abstract
BACKGROUND AND AIM Gastrointestinal bleeding (GIB) often accompanies alcoholic hepatitis (AH). The study aimed to investigate clinical characteristics of GIB in AH patients and to identify risk factors for mortality in AH patients with GIB.
METHODS Data from 329 patients hospitalized with AH in a single center during 1999-2014 were retrospectively analyzed. Patients with AH were dichotomized into GIB and non-GIB groups. The GIB group was further divided into portal hypertensive bleeding (PHB) and non-PHB groups. Clinical characteristics and survival outcomes were compared between the groups. Risk factors for mortality were analyzed using Cox regression.
RESULTS Among the 329 AH patients, 132 experienced GIB at admission or during hospitalization. The most common cause of GIB was an esophageal varix. The GIB group had worse survival outcomes than the non-GIB group (log-rank test, P = 0.034). The PHB group had worse survival outcomes than the non-PHB group (log-rank test, P = 0.001). On multivariate analysis, alcohol consumption, ascites, encephalopathy, infection, Maddrey's discriminant function, and the model for end-stage liver disease (MELD) score independently predicted mortality in the entire AH cohort. The MELD score (hazard ratio, 1.085; 95% confidence interval, 1.052-1.120; P < 0.001) and PHB (hazard ratio, 2.162; 95% confidence interval, 1.021-4.577; P = 0.044) were significant prognosticators for patients with AH and GIB.
CONCLUSIONS The presence of PHB and a higher MELD score adversely affected survival in AH patients with GIB. Accordingly, prompt endoscopic examination for exploring the etiologies of GIB may alert physicians to predict the risk of death in AH patients with GIB.
PubMed IF 3.5 소화기내과
962016

제1저자 옥찬영 · 교신저자 오도연

, , , , , , ,
Metabolic landscape of advanced gastric cancer according to HER2 and its prognostic implications.
Gastric Cancer. 2016;19(2):421-430.

Abstract
BACKGROUND In advanced gastric cancer (AGC), HER2 is a validated therapeutic target. However, the metabolic landscape of AGC based on HER2 status has not been reported. Furthermore, the prognostic value of HER2 in AGC is under debate. The purpose of this study was to determine the metabolic landscape and prognosis on the basis of HER2 status in AGC.
METHODS We analyzed 866 AGC patients treated with palliative chemotherapy and whose HER2 status was evaluated. HER2 positivity was defined as HER2 IHC 3+ or HER2/CEP17 ratio ≥2. Among them, 363 patients were evaluated with (18)F FDG-PET before chemotherapy. We analyzed mSUV (maximal standardized uptake value) according to HER2 status and clinical outcomes.
RESULTS Among 866 patients, 225 (26.0 %) had HER2+ GC. The mSUV of HER2+ GC was significantly higher than that of HER2- GC (12.6 vs. 8.7, p < 0.001). Increased HER2 IHC positivity was correlated with increased mSUV (IHC-: 8.1, IHC 1+: 8.2, 2+: 11.4, 3+: 13.2, p < 0.001). Excluding HER2+ patients who received HER2-targeting agents, OS of patients was not different by HER2 status (12.5 vs. 11.9 months, p = 0.688). However, according to tumor metabolism, patients with higher mSUV showed worse OS regardless of HER2 positivity (mSUV < 12.8:14.8, ≥12.8:8.6 months, p < 0.001).
CONCLUSION Tumor metabolism of AGC adversely influenced OS under treatment with cytotoxic chemotherapy. Tumor metabolism was higher in HER2+ AGC than HER2-. However, HER2 was not a prognostic factor in patients who received chemotherapy without HER2-targeting agents.
PubMed IF 6.1 혈액종양내과
952016

제1저자 옥찬영 · 교신저자 오도연

, , , , , , , ,
Weight loss at the first month of palliative chemotherapy predicts survival outcomes in patients with advanced gastric cancer.
Gastric Cancer. 2016;19(2):597-606.

Abstract
BACKGROUND Weight loss during chemotherapy is a significant prognostic factor for poor survival in patients with advanced gastric cancer (AGC). However, in most studies, weight loss was measured at the end of chemotherapy, limiting its clinical use. In this study, we evaluated whether weight loss during the first month of chemotherapy could predict survival outcomes in patients with AGC.
METHODS We analyzed 719 patients with metastatic or recurrent AGC who were receiving palliative chemotherapy. We calculated the initial body mass index (BMIi), percent weight loss after 1 month of chemotherapy (ΔW 1m), percent weight loss after last administration of chemotherapy (ΔW end), and average weight loss per month during chemotherapy (ΔW/m). We correlated these data with overall survival (OS) by receiver-operating characteristic (ROC) curves and Kaplan-Meier curves, and performed a subgroup analysis using Cox regression.
RESULTS The probabilities of longer OS had stronger correlations with ΔW/m and ΔW 1m than with ΔW end or BMIi. A significant positive correlation between ΔW 1m and ΔW/m (r (2) = 0.591, p < 0.001) was observed. Median OS of patients with ΔW 1m more than 3 % was significantly shorter than in patients with less weight loss (OS: 9.7 vs. 16.3 months, p < 0.001). Subgroup analysis revealed that ΔW 1m accompanied poor survival irrespective of other clinical characteristics.
CONCLUSION Weight loss at the very first month of palliative chemotherapy could predict unfavorable survival outcomes in AGC.
PubMed IF 6.1 혈액종양내과
942016

제1저자 손일석 · 교신저자 오병희

, , , , , , ,
Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial.
Am J Cardiovasc Drugs. 2016;16(2):129-38.

Abstract
BACKGROUND This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).
METHODS In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.
RESULTS A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were -9.50 (8.46) mmHg in the OM/AML/HCTZ group and -4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.
CONCLUSION In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).
PubMed IF 3.2 순환기내과
932016

제1저자 이기형 · 교신저자 오도연, 임석아

, , , , , , , , , , , , , , , , ,
A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.
Support Care Cancer. 2016;24(4):1709-17.

Abstract
PURPOSE Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim.
METHODS In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1.
RESULTS The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly.
CONCLUSIONS Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.
PubMed IF 3.4 혈액종양내과
922016

제1저자 김경임 · 교신저자 윤성수, 오정미

, , , , , , , , , ,
Psychometric analysis of the Korean version of the high-dose chemotherapy specific quality of life questionnaire module from the European Organization for Research and Treatment of Cancer (EORTC QLQ-HDC29).
Qual Life Res. 2016;25(4):881-90.

Abstract
PURPOSE We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer high-dose chemotherapy specific quality of life questionnaire module (EORTC QLQ-HDC29) when implemented with Korean patients by conducting a multicenter, longitudinal study in three Korean hospitals.
METHODS A total of 226 patients who scheduled to receive the HDC followed by hematopoietic stem cell transplantation (HSCT) were enrolled. The patients were asked to complete three questionnaires [the EORTC Core Questionnaire (QLQ-C30), QLQ-HDC29, and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation] at four points in time: before HSCT and 100, 180, and 365 days after HSCT. Standard validity and reliability analyses were performed.
RESULTS Internal consistency of the QLQ-HDC29 was generally acceptable, as tested by Cronbach's α, except for the scales body image and the inpatient issues. Cronbach's α values for the Korean version of the QLQ-HDC29 were almost in accordance with results of the original version, except for the scales body image (lower to the original QLQ-HDC29, α = 0.73) and impact on family (higher to the original QLQ-HDC29, α = 0.52). Known-group comparison analyses showed significantly higher symptom burdens in patients with poor performance status or graft versus host disease (similar to the original QLQ-HDC29). The QLQ-HDC29 indicated good convergent and discriminant validity and showed responsiveness to changes in line with a clinical course over time after HSCT.
CONCLUSIONS The QLQ-HDC29 is generally reliable and adequate to assess QoL in Korean patients undergoing HDC followed by HSCT.
PubMed IF 3.4 혈액종양내과
912016

제1저자 진은효 · 교신저자 김상균

, , , , ,
Clinical outcomes of re-stenting in patients with stent malfunction in malignant gastric outlet obstruction.
Surg Endosc. 2016;30(4):1372-9.

Abstract
BACKGROUND AND AIMS Self-expanding metal stents (SEMS) have been used for the palliative treatment of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the clinical outcomes of salvage SEMS for stent malfunction and to identify the prognostic factors for a longer patency.
METHODS A total of 108 patients who underwent a secondary salvage SEMS placement for a primary stent malfunction were retrospectively reviewed at the Seoul National University Hospital between August 2004 and May 2013. The duration of patency for salvage SEMS was defined as the time between salvage SEMS placement and the recurrence of obstructive symptoms that were confirmed either endoscopically or radiologically.
RESULTS The technical and clinical success rates for salvage SEMS were 100 and 82.4% (95% confidence interval [CI] 74.0-89.0), respectively. A salvage SEMS malfunction occurred in 29 (26.9%) of the 108 patients. The median duration of patency for salvage SEMS was 59.5 days (range 3-928, 95% CI 73.7-118.3). Longer SEMS patencies of more than 60 days were significantly associated with palliative chemotherapy (odds ratio = 2.539, 95% CI 1.031-6.252, p = .043). For salvage SEMS, covered-uncovered stents had a longer patency duration, as compared with other combinations of primary and salvage stent types.
CONCLUSIONS Longer patency durations for salvage SEMS were associated with palliative chemotherapy after salvage SEMS insertion. Salvage SEMS could be a feasible and effective treatment for primary stent malfunction in malignant GOO.
PubMed IF 3.3 소화기내과
902016

제1저자 김세중 · 교신저자 이춘택

, , , , , , , , , ,
Factors associated with preserved pulmonary function in non-small-cell lung cancer patients after video-assisted thoracic surgery.
Eur J Cardiothorac Surg. 2016;49(4):1084-90.

Abstract
OBJECTIVES Some non-small-cell lung cancer patients have preserved pulmonary function after surgery. Compared with open thoracotomy, video-assisted thoracic surgery (VATS) is widely performed and preserves pulmonary function. Patients with non-small-cell lung cancer have an extremely poor prognosis without surgery. Clinicians should therefore decide which patients can safely tolerate lung resection. This study aimed to identify factors associated with preserving pulmonary function after VATS in non-small-cell lung cancer patients.
METHODS Three hundred and fifty-one patients with non-small-cell lung cancer underwent VATS and preoperative and 12-month postoperative pulmonary function tests. Patients with and patients without preserved forced expiratory volume in 1 s (FEV1) and diffusing capacity of carbon monoxide were compared.
RESULTS The FEV1 was preserved after VATS in 142 (40.5%) patients. In multivariable analysis, this group was significantly associated with VATS sublobar resection (P < 0.001) and resection at the right upper lobe or right middle lobe (vs right lower lobe, P = 0.048; vs left upper lobe, P = 0.003; vs left lower lobe, P = 0.015). Diffusing capacity of carbon monoxide was preserved in 129 (36.8%) patients. Multivariable analysis showed that VATS sublobar resection (P < .001), lower baseline diffusing capacity of carbon monoxide (P < 0.001) and right upper lobe or right middle lobe resection (vs right lower lobe, P = 0.0014; vs left upper lobe, P = 0.029, vs left lower lobe, P = 0.014) were significantly associated with preserved diffusing capacity of carbon monoxide.
CONCLUSIONS For preserving pulmonary function after non-small-cell lung cancer surgery, VATS sublobar resection was superior to VATS lobectomy, and surgery on the right upper lobe or right middle lobe was superior to that at other sites.
PubMed IF 3.3 호흡기내과
892016

제1저자 신철민 · 교신저자 김나영

, , , , ,
Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication.
Dig Dis Sci. 2016;61(4):1051-9.

Abstract
BACKGROUND Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet.
AIMS To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM).
METHODS Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up.
RESULTS Average follow-up duration was 33.7 months (range 2-97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (ρ = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015).
CONCLUSIONS In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression.
PubMed IF 2.8 소화기내과
882016

제1저자 김병근 · 교신저자 강혜련

, , , , , , ,
Allergies are still on the rise? A 6-year nationwide population-based study in Korea.
Allergol Int. 2016;65(2):186-191.

Abstract
BACKGROUND Some western countries recently have shown a slowdown in the incidence of allergic diseases after worldwide increasing trends, but there are few data from Asian populations concerning changing trend of allergic diseases. We evaluated the recent trends in the prevalence of asthma and other allergic diseases in Korea.
METHODS From the database of Korean National Health Insurance, a nationwide diagnostic data from 2009 to 2014 were extracted and the national prevalence was analyzed.
RESULTS The prevalence per 1000 people of atopic dermatitis, allergic rhinitis, and asthma in 2014 was 19.0, 133.1, and 36.3, respectively. The prevalence of three diseases was highest in the age group under 10 as, 95.0, 384.1, and 132.1 per 1000 people, while the prevalence in the over-10-year-group was only 11.6, 109.5, and 27.3, respectively. The prevalence of atopic dermatitis and allergic rhinitis gradually decreased with older age, but the prevalence of asthma showed a re-increasing pattern from the age group 30-39 and reached another peak for the age group 70-79. During the study period, the prevalence of asthma and atopic dermatitis showed decreasing tendency. In contrast, the prevalence of allergic rhinitis steadily increased until 2013, especially in the age group under 10.
CONCLUSIONS The national prevalence of atopic dermatitis, and asthma did not show noticeable increase any more in Korea. However, the prevalence of allergic rhinitis still on the rise until recently, especially in the age group under 10. This is the first report in Asia suggesting a slowdown of the incidence of allergic diseases.
PubMed IF 6.2 알레르기내과
872016

제1저자 최진우 · 교신저자 박경수

, , , , , , ,
DMC (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) improves glucose tolerance as a potent AMPK activator.
Metabolism. 2016;65(4):533-42.

Abstract
OBJECTIVE We investigated the effect and regulatory mechanism of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from Cleistocalyx operculatus on metabolic parameters in myotubes, adipocytes and an obese mouse model.
MATERIALS AND METHODS Myotubes and adipocytes were incubated with or without DMC. Glucose uptake, fatty acid oxidation, AMPK activation and adipocytes differentiation were investigated. To examine in vivo effect of DMC, 30mg/kg/day DMC was administered by oral gavage for 2weeks in high fat fed C57BL/6 male mice and intra-peritoneal glucose tolerance test was performed. In order to examine whether DMC directly activates AMPK, we performed cell free AMPK assay and surface plasmon resonance spectroscopy analysis.
RESULT DMC increases glucose uptake and fatty acid oxidation (FAO) in myotubes. Also, DMC inhibits adipocyte differentiation in 3T3-L1 cells. Interestingly, DMC stimulates phosphorylation of AMP-dependent protein kinase (AMPK) alpha subunit (T172) by directly binding to AMPK, which results in the activation of AMPK. Furthermore, DMC binds AMPK with a higher affinity than AMP. When AMPK was knocked down, the stimulatory effect of DMC on FAO and its inhibitory effect on adipogenesis were abolished. These results suggest that the effects of DMC were primarily mediated by AMPK activation. In addition, treating mice fed a high fat diet with DMC improved glucose tolerance and significantly increased FAO of the muscles.
CONCLUSION DMC, as a novel AMPK activator, shows anti-diabetic effects in cell culture systems, such as myotubes and adipocytes, and in a diet-induced obese mouse model.
PubMed IF 16.7 내분비대사내과
862016

제1저자 오태정 · 교신저자 조영민

, ,
Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: Lessons from ileal transposition surgery.
J Diabetes Investig. 2016;7 Suppl 1(Suppl 1):94-101.

Abstract
Roux-en Y gastric bypass is a highly effective bariatric/metabolic surgical procedure that can induce robust weight loss and even remission of type 2 diabetes. One of the characteristic consequences of Roux-en Y gastric bypass is the expedited nutrient delivery to the distal small intestine, where L-cells are abundant and bile acid reabsorption occurs. To examine the role of the distal small intestine in isolation from other components of Roux-en Y gastric bypass, the ileal transposition (IT) surgery has been used in various rat models. IT relocates the distal ileal segment to the upper jejunum distal to the ligament of Treitz without any other alterations in the gastrointestinal anatomy. Therefore, IT exposes the distal ileal tissue to ingested nutrients after a meal faster than the normal condition. Although there is some inconsistency in the effect of IT according to different types of rat models and different types of surgical protocols, IT typically improved glucose tolerance, increased insulin sensitivity and induced weight loss, and the findings were more prominent in obese diabetic rats. Suggested mechanisms for the metabolic improvements after IT include increased L-cell secretion (e.g., glucagon-like peptides and peptide YY), altered bile acid metabolism, altered host-microbial interaction, attenuated metabolic endotoxemia and many others. Based on the effect of IT, we can conclude that the contribution of the distal small intestine to the metabolic benefits of bariatric/metabolic surgery is quite considerable. By unveiling the mechanism of action of IT, we might revolutionize the treatment for obesity and type 2 diabetes.
PubMed IF 3.6 내분비대사내과
852016

제1저자 나선희 · 교신저자 김홍빈

, , , , , , , , , , , , ,
Impact of the multiplex polymerase chain reaction in culture-positive samples on appropriate antibiotic use in patients with staphylococcal bacteremia.
Diagn Microbiol Infect Dis. 2016;84(4):353-7.

Abstract
Rapid identification of the microorganisms in patients with bacteremia may be useful in clinical practice. We evaluated the impact of the multiplex polymerase chain reaction (PCR) on appropriate antibiotic use for patients with gram-positive cocci cluster (GPCC) bacteremia. We divided the GPCC bacteremia cases into a pre-PCR group (2010-2011) and a post-PCR group (2012-2013). A total 664 cases were included in the pre-PCR group; and 570, in the post-PCR group. In methicillin-susceptible Staphylococcus aureus (MSSA) cases, optimal antibiotics were administered earlier in the post-PCR group (77.4h versus 42.6h, P=0.035). Although the proportions of glycopeptide exposure did not differ (54.7% versus 56.7%, P=0.799), the duration of exposure decreased (69.6h versus 30.7h, P=0.004). In methicillin-resistant S. aureus cases, the time to optimal antibiotics administration did not differ (45.4h versus 43.7h, P=0.275). Multiplex PCR test significantly improved the early initiation of optimal antibiotics in MSSA bacteremia and reduced the unnecessary glycopeptide exposure.
PubMed IF 1.8 감염내과
842016

제1저자 정경연, 김석모 · 교신저자 박영주, 장항석

, , , , , , , , , , , , , , , , , , ,
Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years.
Clin Endocrinol (Oxf). 2016;84(4):587-97.

Abstract
CONTEXT The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC).
OBJECTIVE We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors.
DESIGN This was a retrospective analysis from 1982 to 2012.
PATIENTS Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012).
MEASUREMENTS These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin.
RESULTS Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po-BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po-BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14-472·11; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 cm (HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality.
CONCLUSIONS Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival.
PubMed IF 2.8 내분비대사내과
832016

제1저자 백규현 · 교신저자 김재환

, , , , , , , , ,
Risk Factors for Gallstone Formation in Resected Gastric Cancer Patients.
Medicine (Baltimore). 2016;95(15):e3157.

Abstract
Previous studies reported increased incidence of gallstone formation after gastrectomy. However, there were few reports about factors other than surgical technique. The purpose of this study is to investigate the spectrum of risk factors of gallstone formation after gastrectomy. From June 2003 to December 2008, 1480 patients who underwent gastrectomy due to gastric cancer but had no gallstones before surgery were identified. Electronic medical records were retrospectively reviewed. Gallstones were assessed by computerized tomography or ultrasound performed as surveillance for recurrence. There were 987 men (66.7%) and the median age was 59.0 years. The median follow-up period was 47.0 months. According to the surgical technique, 754 (50.9%), 459 (31.1%), and 267 (18.0%) underwent subtotal gastrectomy with Billroth I (STG B-I) and Billroth II (STG B-II) anastomosis, and total gastrectomy (TG). Within the follow-up period, gallstone formation occurred in 106 of 1480 patients (7.2%), the only 9 patients (0.6%) experienced symptomatic cholecystitis. By multivariate Cox regression analysis, age (HR 1.02, 95% CI 1.00-1.04), male (1.65, 1.02-2.67), diabetes mellitus (2.15, 1.43-3.24), ≥4% decrease of body mass index after surgery (1.66, 1.02-2.70), STG B-II (1.63, 1.03-2.57), and TG (2.35, 1.43-3.24) compared with STG B-I were associated with gallstone formation. Common bile duct stone formation occurred in 20 of 1480 patients (1.4%) and was only associated with gallstones. After gastrectomy, there were considerable numbers of patients with newly developed gallstones; however, prophylactic cholecystectomy should not be routinely recommended. Gastrectomy (STG B-II or TG), old age, male sex, diabetes mellitus, and decreased body mass index were associated with gallstones.
PubMed IF 2 소화기내과
822016

제1저자 안영미 · 교신저자 이해영

, , , , , , , , , ,
Influence of initial angiotensin receptor blockers on treatment persistence in uncomplicated hypertension: A nation-wide population-based study.
Clin Exp Hypertens. 2016;38(3):325-30.

Abstract
We identified 55 504 uncomplicated, treatment-naïve hypertensive patients who started angiotensin II receptor blockers (ARBs) in 2012 from national claims data. The proportion of patients remaining on any hypertension treatment at 12 months and the adherence rate were similar between the losartan cohort (66.82% and 68.25%) and the nonlosartan ARB cohort (67.48% and 69.01%). After adjusting for confounding factors, there was no difference in persistence (aHR 0.98, 95% confidence interval (CI) 0.95-1.01) on hypertension treatment between losartan and nonlosartan ARB cohort. Post hoc analysis showed that patients initially prescribed eprosartan, irbesartan (both, aHR 1.33), and telmisartan (aHR 1.11) were more likely to discontinue the initial drug, whereas valsartan initiators (aHR 0.96) were less likely compared with losartan initiators.
PubMed IF 6.8 순환기내과
812016

제1저자 옥찬영, 김세희 · 교신저자 김범석

, , , , , , , , , , , , , ,
PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma.
Oncotarget. 2016;7(13):15901-14.

Abstract
Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.
PubMed IF 5.008 혈액종양내과
802016

제1저자 박준원 · 교신저자 이은영

, , , , , ,
Low dose etanercept treatment for maintenance of clinical remission in ankylosing spondylitis.
Clin Exp Rheumatol. 2016;34(4):592-9.

Abstract
OBJECTIVES To investigate the efficacy and safety of low-dose etanercept treatment after clinical remission of ankylosing spondylitis (AS) in the real world.
METHODS Data on 134 AS patients who were treated with etanercept for more than 12 months and achieved clinical remission (BASDAI<4 and CRP<0.5 mg/dL) were extracted from a large single centre registry. Drug survival and incidence of adverse events in 100 patients who reduced the dose during follow up (low-dose group) were compared with 34 patients who maintained the initial dose (standard-dose group). For minimisation of selection bias between the two groups, the same analyses were performed in a propensity score-matched population.
RESULTS Both groups showed similar BASDAI score and CRP levels during the follow-up. Drug survivals between the two groups were also comparable up to 4 years (vs. standard-dose group, adjusted HR=0.472, 95% CI 0.155-1.435). The same analysis performed after propensity score-matching showed concordant result. The incidence of injection site reactions in the low-dose group was significantly lower, and the incidence of other adverse events showed no differences between the two groups. In the low-dose group, dose reduction after more than 24 weeks of standard-dose treatment was associated with longer drug survival (adjusted HR=0.261, 95% CI 0.084-0.809).
CONCLUSIONS Low-dose etanercept treatment after achieving clinical remission can be an alternative treatment option in terms of its comparable long-term efficacy and favourable safety in AS. More than 24 weeks of standard-dose treatment before dose reduction may be beneficial for longer drug survival in this strategy.
PubMed IF 3.2 류마티스내과
792016

제1저자 이종찬 · 교신저자 황진혁

, , , , , ,
Clinical impact of neoadjuvant treatment in resectable pancreatic cancer: a systematic review and meta-analysis protocol.
BMJ Open. 2016;6(3):e010491.

Abstract
INTRODUCTION Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs.
METHOD AND ANALYSIS This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I(2)-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger's test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
ETHICS AND DISSEMINATION This review does not use primary data, and formal ethical approval is not required. Findings will be disseminated through peer-reviewed journals and committee conferences.
TRIAL REGISTRATION NUMBER CRD42015023820.
PubMed IF 2.5 소화기내과
782016

제1저자 김세중 · 교신저자 Shuichi Takayama

, , , , , ,
Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip.
Biofabrication. 2016;8(1):015021.

Abstract
Nephrotoxicity is often underestimated because renal clearance in animals is higher compared to in humans. This paper aims to illustrate the potential to fill in such pharmacokinetic gaps between animals and humans using a microfluidic kidney model. As an initial demonstration, we compare nephrotoxicity of a drug, administered at the same total dosage, but using different pharmacokinetic regimens. Kidney epithelial cell, cultured under physiological shear stress conditions, are exposed to gentamicin using regimens that mimic the pharmacokinetics of bolus injection or continuous infusion in humans. The perfusion culture utilized is important both for controlling drug exposure and for providing cells with physiological shear stress (1.0 dyn cm(-2)). Compared to static cultures, perfusion culture improves epithelial barrier function. We tested two drug treatment regimens that give the same gentamycin dose over a 24 h period. In one regimen, we mimicked drug clearance profiles for human bolus injection by starting cell exposure at 19.2 mM of gentamicin and reducing the dosage level by half every 2 h over a 24 h period. In the other regimen, we continuously infused gentamicin (3 mM for 24 h). Although junctional protein immunoreactivity was decreased with both regimens, ZO-1 and occludin fluorescence decreased less with the bolus injection mimicking regimen. The bolus injection mimicking regimen also led to less cytotoxicity and allowed the epithelium to maintain low permeability, while continuous infusion led to an increase in cytotoxicity and permeability. These data show that gentamicin disrupts cell-cell junctions, increases membrane permeability, and decreases cell viability particularly with prolonged low-level exposure. Importantly a bolus injection mimicking regimen alleviates much of the nephrotoxicity compared to the continuous infused regimen. In addition to potential relevance to clinical gentamicin administration regimens, the results are important in demonstrating the general potential of using microfluidic cell culture models for pharmacokinetics and toxicity studies.
PubMed IF 8.2 신장내과
772016

제1저자 장은선 · 교신저자 정숙향

, , , , ,
Diagnostic Performance of Alpha-Fetoprotein, Protein Induced by Vitamin K Absence, Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma.
PLoS One. 2016;11(3):e0151069.

Abstract
BACKGROUND & AIMS Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance.
METHODS Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers.
RESULTS Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient's age, etiology and tumor invasiveness of HCC affected the performance of each marker.
CONCLUSIONS AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.
PubMed IF 2.8 소화기내과
762016

제1저자 이주명 · 교신저자 구본권

, , , , , , , , ,
Coronary Flow Reserve and Microcirculatory Resistance in Patients With Intermediate Coronary Stenosis.
J Am Coll Cardiol. 2016;67(10):1158-1169.

Abstract
BACKGROUND The prognostic impact of microvascular status in patients with high fractional flow reserve (FFR) is not clear.
OBJECTIVES The goal of this study was to investigate the implications of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients who underwent FFR measurement.
METHODS Patients with high FFR (>0.80) were grouped according to CFR (≤2) and IMR (≥23 U) levels: group A, high CFR with low IMR; group B, high CFR with high IMR; group C, low CFR with low IMR; and group D, low CFR with high IMR. Patient-oriented composite outcome (POCO) of any death, myocardial infarction, and revascularization was assessed. The median follow-up was 658 days (interquartile range: 503.8 to 1,139.3 days).
RESULTS A total of 313 patients (663 vessels) were assessed with FFR, CFR, and IMR. Correlation (r = 0.201; p < 0.001) and categorical agreement (kappa value = 0.178; p < 0.001) between FFR and CFR were modest. Low CFR was associated with higher POCO than high CFR (p = 0.034). There were no significant differences in clinical and angiographic characteristics among groups. Patients with high IMR with low CFR had the highest POCO (p = 0.002). Overt microvascular disease (p = 0.008), multivessel disease (p = 0.033), and diabetes mellitus (p = 0.033) were independent predictors of POCO. Inclusion of a physiological index significantly improved the discriminant function of a predictive model (relative integrated discrimination improvement 0.467 [p = 0.037]; category-free net reclassification index 0.648 [p = 0.007]).
CONCLUSIONS CFR and IMR improved the risk stratification of patients with high FFR. Low CFR with high IMR was associated with poor prognosis. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).
PubMed IF 22.3 순환기내과
752016

제1저자 하혜림 · 교신저자 오도연

, , , , , , , , , , , ,
Survival Outcomes According to Adjuvant Treatment and Prognostic Factors Including Host Immune Markers in Patients with Curatively Resected Ampulla of Vater Cancer.
PLoS One. 2016;11(3):e0151406.

Abstract
BACKGROUND Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca.
METHODS AND FINDINGS We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9-129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11-2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00-2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13-2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20-5.53) and elevated CA 19-9 (HR 1.794, 95% CI: 1.07-3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%).
CONCLUSIONS Vascular invasion and elevated CA 19-9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors.
PubMed IF 2.8 혈액종양내과
742016

제1저자 육정환, 김효리 · 교신저자 김태용, 임석아

, , , , , , , , , , , , , , , ,
Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.
J Cancer Res Clin Oncol. 2016;142(3):707-14.

Abstract
PURPOSE In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy.
METHODS Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics.
RESULTS A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008).
CONCLUSIONS High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.
PubMed IF 3.3 혈액종양내과
732016

제1저자 윤혁 · 교신저자 김나영

, , , , , , , , ,
Risk Factors for Metachronous Gastric Neoplasms in Patients Who Underwent Endoscopic Resection of a Gastric Neoplasm.
Gut Liver. 2016;10(2):228-36.

Abstract
BACKGROUND/AIMS To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm.
METHODS We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms.
RESULTS A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 highgrade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020).
CONCLUSIONS In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.
PubMed IF 4.1 소화기내과
722016

제1저자 김광일 · 교신저자 진호준

, , , , ,
Low Hemoglobin A1c Increases the Risk of Disability in Community-dwelling Older Non-diabetics Adults.
J Nutr Health Aging. 2016;20(3):341-6.

Abstract
OBJECTIVE To describe the health characteristics of individuals with low HbA1c levels and evaluate the association between HbA1c level and disability or all-cause mortality in non-diabetic older adults.
DESIGN Prospective observational cohort study.
SETTING Seongnam, Gyeongi Province, Korea.
PARTICIPANTS Among the 1,000 community-dwelling Koreans ≥ 65 years of age who were followed for 5 years, 760 non-diabetic individuals were analyzed.
MEASUREMENTS Activities of Daily Living (ADL) and Instrumental ADL (IADL) were evaluated and mortality data were obtained from the National Statistics Office of Korea.
RESULTS The mean age was 76.3 (SD 9.0) years, and 319 subjects (42.0%) were male. Lower level of HbA1c was associated with less frequent hypertension and less frequent use of aspirin or statin, and lower values of body mass index, hematocrit, total iron-binding capacity, albumin, and cholesterol level. The participants were categorized into 3 groups according to their HbA1c (group I, < 5.5%; group II, 5.5~5.9%; and group III, 6.0 ~ 6.4%). Although, there was no significant difference in functional status according to baseline HbA1c level, disability was more frequently observed as the HbA1c level decrease (18.3% in group I, 12.5% in group II, and 5.3% in group III, p=0.029) at the 5-year follow-up evaluation. There were 172 deaths (22.6%) during the follow-up period. There was no significant difference in mortality among the groups, however, group I had a 2.071-fold higher risk for the incident disability or mortality over group III after adjusting age, gender, and possible confounder (95% CI: 1.040 ~ 4.124, p=0.038).
CONCLUSIONS Lower level of HbA1c was associated with an increased risk of disability in non-diabetic older adults.
PubMed IF 5 신장내과
712016

제1저자 이도영 · 교신저자 박영주, 하정훈

, , , , , , , , ,
Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.
Thyroid. 2016;26(3):404-13.

Abstract
BACKGROUND This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC).
METHODS A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci.
RESULTS The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013).
CONCLUSIONS The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.
PubMed IF 6.6 내분비대사내과
702016

제1저자 홍아람, 김정희 · 교신저자 신찬수

, , , ,
Trabecular bone score as a skeletal fragility index in acromegaly patients.
Osteoporos Int. 2016;27(3):1123-1129.

Abstract
SUMMARY Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients.
INTRODUCTION Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients.
METHODS We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis.
RESULTS Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P < 0.05), although BMD at all sites were similar for the two groups. In eugonadal acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041).
CONCLUSIONS Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.
PubMed IF 5.4 내분비대사내과
692016

제1저자 김정희 · 교신저자 신찬수

, , , , , , ,
Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women.
Osteoporos Int. 2016;27(3):1161-1168.

Abstract
SUMMARY In a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat.
INTRODUCTION The effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women.
METHODS Cross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA).
RESULTS In an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = -0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (β = -0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (β = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution.
CONCLUSION Our findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.
PubMed IF 5.4 내분비대사내과
682016

제1저자 정경연, 김경민 · 교신저자 임수

, , , , , , , , ,
Age- and sex-specific association of circulating osteocalcin with dynamic measures of glucose homeostasis.
Osteoporos Int. 2016;27(3):1021-1029.

Abstract
SUMMARY Our study showed that serum osteocalcin levels are closely related to glucose metabolism in men of all ages and younger women. This association disappeared in postmenopausal women in which increases bone turnover rates. The association between serum osteocalcin levels and glucose homeostasis should be interpreted according to age and sex.
INTRODUCTION Osteocalcin, a marker of bone formation, appears to be associated with glucose homeostasis. We investigated the age- and sex-specific association of serum osteocalcin level with variables related to glucose metabolism.
METHODS This study was based on cross-sectional analysis from 719 participants aged 20-85 years after excluding patients taking antidiabetic or antiosteoporotic drugs. The subjects were divided into four groups according to age and sex as follows: men <50 years (n = 131), men ≥50 years (n = 191), women <50 years (n = 108), and women ≥50 years (n = 279). Anthropometric and biochemical variables including insulin resistance (HOMA-IR) and β cell function (HOMA-β) from a 75-g oral glucose tolerance test, and serum 25-OH-vitamin D and parathyroid hormone levels were measured.
RESULTS The serum osteocalcin level was significantly higher in women aged ≥50 years compared with women <50 years (20.4 ± 7.8 vs. 17.9 ± 6.8 ng/ml, p < 0.001), but there was no difference between men aged ≥50 years and men <50 years (16.4 ± 5.9 vs. 16.8 ± 6.0 ng/ml, p = 0.905). The participants diagnosed with diabetes had lower serum osteocalcin levels than normal or prediabetic participants. Multivariable regression analyses including HOMA-IR and HOMA-β indicated that serum osteocalcin levels had a negative and independent association with HbA1c levels in men and women aged <50 years, but not in women ≥50 years.
CONCLUSIONS Low osteocalcin levels are associated with impaired glucose metabolism in men and premenopausal women. The osteocalcin levels may be determined by factors related to bone metabolism in postmenopausal women. Our data suggest that the serum levels of osteocalcin associated with glucose homeostasis should be interpreted according to age and sex.
PubMed IF 5.4 내분비대사내과

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