SCI 발표논문
전체 4,588편
- 20982016
제1저자 허진 · 교신저자 김효수
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KAI1(CD82)-DARC(CD234) axis in the stem cell niche.Cell Cycle. 2016;15(15):1945-7.
- 20972016
제1저자 박효은, 곽민선 · 교신저자 최수연, 김동희
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Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study.J Clin Endocrinol Metab. 2016;101(8):3134-43.
PubMed IF 5.4 소화기내과Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown.
OBJECTIVE This study investigated the longitudinal association between NAFLD and CAC score.
DESIGN AND SETTING This study is a longitudinal cohort study performed in a healthcare center.
PARTICIPANTS Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography.
MAIN OUTCOME MEASURES CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed.
RESULTS More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043).
CONCLUSIONS NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.
- 20962016
제1저자 최수연 · 교신저자 성지동
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Combined effects of exercise capacity and coronary atherosclerotic burden on all-cause mortality in asymptomatic Koreans.Atherosclerosis. 2016;251:396-403.
PubMed IF 7.1 순환기내과Abstract
BACKGROUND AND AIMS Both exercise capacity and coronary artery calcium score (CACS) are important prognostic factors in cardiovascular outcome. Yet, whether there is a significant interaction between these two factors in influencing clinical outcome is still uncertain. This study investigated the combined effects of exercise capacity and CACS on all-cause mortality in an asymptomatic population.
METHODS From multicenter registry of health screening, a retrospective cohort of 25,972 asymptomatic subjects, who underwent both CACS and treadmill exercise test, was included in the final dataset for analysis. Outcome was defined as all-cause mortality, which was obtained from national mortality registry.
RESULTS The mean age of study subjects was 53.7 ± 7.7 years and 81.5% of them were males. Median follow-up duration was 5.5 (IQR 3.6-7.5) years and 226 (0.9%) cases of all-cause mortality occurred. In multivariate Cox's proportional hazard model with interaction term, exercise capacity ≥10 METs (HR 0.684, 95% CI 0.483-0.971) and CACS ≥400 (HR 3.328, 95% CI 1.850-5.988) were significant predictors of all-cause mortality. In patients with higher exercise capacity, the effect of high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. The HR for all-cause mortality of CACS ≥400, in those with lower exercise capacity, is estimated to be about three times of that in those with higher exercise capacity (HR 3.328 in <10 METs vs. 1.108 in ≥10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, creatinine, alanine transaminase and albumin.
CONCLUSIONS The effect of high CACS on all-cause mortality is lessened by good exercise capacity in the asymptomatic population. Good physical fitness may reduce the adverse effect of high coronary atherosclerotic burden.
- 20952016
제1저자 강지훈,허진,강진아 · 교신저자 김효수
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Priming mobilized peripheral blood mononuclear cells with the "activated platelet supernatant" enhances the efficacy of cell therapy for myocardial infarction of rats.Cardiovasc Ther. 2016;34(4):245-53.
PubMed IF 2.8 순환기내과Abstract
AIM Various methods are used to augment the efficacy of cell therapy in myocardial infarction (MI). In this study, we used the "activated platelet supernatant (APS)" to prime autologous "granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells ((mob) PBMCs)" and investigated the efficacy of cell-based therapy in MI.
METHOD Rat (mob) PBMCs were isolated after daily subcutaneous injections of G-CSF at 100 μg/kg for 3 days. APS was isolated separately after activating rat platelets with thrombin 0.5 U/mL for 2 hours. Priming was performed with APS for 6 hours. To check the paracrine effect of primed (mob) PBMCs, we used the 36-hour culture supernatant of the primed cells. A rat MI model was used for an in vivo model.
RESULT Cytokines such as IL-1β, IL-10, and TGFβ were 3.7±0.9-fold, 3.4±1.2-fold, and 1.2±0.1-fold higher in APS, respectively, compared with naïve platelet supernatant. By APS priming, (mob) PBMCs showed M2 polarization and upregulation of angiogenic molecules (i.e., TEK, IL-10, CXCL1, and CX3CR1). APS-primed (mob) PBMCs had a 2.3-fold increased adhesion ability, induced by upregulated integrins. Rat endothelial cells cultured in the 36-hour culture supernatant of APS-primed (mob) PBMCs showed a 1.6-fold augmented proliferation and capillary network formation. In vivo transplantation of APS-primed (mob) PBMCs into rat MI models showed a significant trend of reduction in fibrosis area (P=.001) and wall thinning (P=.030), which lead to improvement in cardiac function measured by echocardiography.
CONCLUSION Our data reveal that APS priming can enhance the wound-healing potential of (mob) PBMCs. APS priming may be a promising method for cell-based therapy of MI.
- 20942016
제1저자 박진균 · 교신저자 이은봉
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Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial.Clin Ther. 2016;38(8):1858-1868.e2.
PubMed IF 3.7 류마티스내과Abstract
PURPOSE The aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA).
METHODS A randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization.
FINDINGS The allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (-9.0 [-23.8 to -0.4] vs -2.2 [-16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI-defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles.
IMPLICATIONS GCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116.
- 20932016
제1저자 박종선 · 교신저자 이상민
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Anti-inflammatory Effect of Erdosteine in Lipopolysaccharide-Stimulated RAW 264.7 Cells.Inflammation. 2016;39(4):1573-81.
PubMed IF 5.4 호흡기내과Abstract
Erdosteine is widely used as a mucolytic agent and also has free radical scavenging and antioxidant activities. However, little is known about the mechanisms of the anti-inflammatory effect of erdosteine. We investigated the effect of erdosteine on the activation of the nuclear factor (NF)-kB/inhibitor of NFkB (IkB), and the mitogen-activated protein kinase (MAPK) and Akt pathways in the mouse macrophage cell line RAW 264.7. Cultured RAW 264.7 cells were pretreated with erdosteine and stimulated with lipopolysaccharide (LPS). In Western blotting, pretreatment with erdosteine inhibited the IkBα degradation induced in RAW 264.7 cells by LPS. LPS-induced IkB kinase (IKK) activity and NF-kB transcription were inhibited by pretreatment with erdosteine. Production of IL-6 and IL-1β was also inhibited by erdosteine pretreatment. However, erdosteine did not inhibit LPS-induced phosphorylation of Akt and MAPKs. These results suggest that the anti-inflammatory effect of erdosteine in mouse macrophages is mediated through inhibition of LPS-induced NF-kB activation.
- 20922016
제1저자 장동기 · 교신저자 류지곤
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Risk Factors for Progression or Malignancy in Main-Duct and Mixed-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas.Pancreas. 2016;45(7):1027-31.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy.
METHODS Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion.
RESULTS Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy.
CONCLUSIONS A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.
- 20912016
제1저자 박재윤 · 교신저자 이정표
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Superior outcomes of kidney transplantation compared with dialysis: An optimal matched analysis of a national population-based cohort study between 2005 and 2008 in Korea.Medicine (Baltimore). 2016;95(33):e4352.
PubMed IF 2 신장내과Abstract
Data regarding kidney transplantation (KT) and dialysis outcomes are rare in Asian populations. In the present study, we evaluated the clinical outcomes associated with KT using claims data from the Korean national public health insurance program. Among the 35,418 adult patients with incident dialysis treated between 2005 and 2008 in Korea, 1539 underwent KT. An optimal balanced risk set matching was attempted to compare the transplant group with the control group in terms of the overall survival and major adverse cardiac event-free survival. Before matching, the dialysis group was older and had more comorbidities. After matching, there were no differences in age, sex, dialysis modalities, or comorbidities. Patient survival was significantly better in the transplant group than in the matched control group (P < 0.001). In addition, the transplant group showed better major adverse cardiac event-free survival than the dialysis group (P < 0.001; hazard ratio, 0.49; 95% confidence interval, 0.32-0.75). Korean patients with incident dialysis who underwent long-term dialysis had significantly more cardiovascular events and higher all-cause mortality rates than those who underwent KT. Thus, KT should be more actively recommended in Korean populations.
- 20902016
제1저자 유수종 · 교신저자 윤정환
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Percutaneous ethanol injection therapy is comparable to radiofrequency ablation in hepatocellular carcinoma smaller than 1.5 cm: A matched case-control comparative analysis.Medicine (Baltimore). 2016;95(35):e4551.
PubMed IF 2 소화기내과Abstract
Although percutaneous ethanol injection therapy (PEIT) is best indicated for patients with small hepatocellular carcinoma (HCC), the survival advantage of PEIT needs confirmation in real-world practice. This study was approved by the institutional review board, and the informed consent was waived. The study included 535 consecutive patients with newly diagnosed early stage (Barcelona Clinic Liver Cancer [BCLC] 0 or A) HCC who underwent initially radiofrequency ablation (RFA) (n = 288) or PEIT (n = 247) from January 2005 to December 2010. The primary outcome was overall survival (OS) and the secondary outcome was time to progression (TTP). The longest diameters of tumors of the groups differed significantly and larger for RFA group than PEIT group (P < 0.001; 1.94 ± 0.65 cm vs 1.60 ± 0.50 cm, respectively). The 5-year OS rates were 72.2% in the RFA group and 67.4% in the PEIT group (P = 0.608). Even after propensity score matching, OS rates between the 2 groups were similar (5-year OS: 72.8% with RFA [n = 175] and 68.0% with PEIT [n = 175]) (P = 0.709). Moreover, in patients with the longest diameter of tumors (≤1.5 cm), multivariate Cox regression analysis showed that the treatment modality was not a significant prognosticator for OS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 0.828-3.449; P = 0.149) and time to progression (HR, 1.160; 95% CI, 0.773-1.740; P = 0.474). PEIT and RFA show equal effectiveness in treating HCCs <1.5 cm in terms of OS and time to progression.
- 20892016
제1저자 한정규 · 교신저자 김효수
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Interaction between platelets and endothelial progenitor cells via LPA-Edg-2 axis is augmented by PPAR-δ activation.J Mol Cell Cardiol. 2016;97:266-77.
PubMed IF 4.9 순환기내과Abstract
BACKGROUND Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor regulating cell metabolism. The role of PPAR-δ in late endothelial progenitor cells (EPCs) has not been fully elucidated. We aim to understand the effects of PPAR-δ activation on late EPC and to reveal the underlying mechanism.
METHODS AND RESULTS Treatment with a highly selective PPAR-δ agonist (GW501516) induced proliferation of late EPCs and enhanced their vasculogenic potential. Search for the target molecule of PPAR-δ activation revealed endothelial differentiation gene (Edg)-2. Chromatin immunoprecipitation and promoter assays demonstrated that Edg-2 gene was specifically induced by PPAR-δ through direct transcriptional activation. Lysophosphatidic acid (LPA), an Edg ligand, mimicked the pro-vasculogenic effects of GW501516 in late EPCs whereas Edg antagonist (Ki16425) blocked these effects. Edg-2 is a membrane receptor for LPA which is a major growth factor from activated platelets. Thus, the interaction between platelets and late EPCs via the LPA-Edg-2 axis was assessed. Platelet supernatant boosted the pro-vasculogenic effects of GW501516, which was reversed by antagonist to PPAR-δ (GSK0660) or Edg (Ki16425). Both of in vivo Matrigel plug model and mouse skin punch-wound model demonstrated that the combination of platelets and PPAR-δ-activated late EPCs synergistically enhanced vascular regeneration.
CONCLUSIONS There exists a synergistic interaction between human platelets and late EPCs leading to vascular regeneration. This interaction consists of LPA from platelets and its receptor Edg-2 on the surface of EPCs and can be potentiated by PPAR-δ activation in EPCs. A PPAR-δ agonist is a good candidate to achieve vasculogenesis for ischemic vascular disease.
- 20882016
제1저자 이주엽 · 교신저자 김나영
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Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth quadruple therapy for the first-line eradication of Helicobacter pylori: a prospective, multi-center, randomized clinical trial.BMC Gastroenterol. 2016;16(1):79.
PubMed IF 3.2 소화기내과Abstract
BACKGROUND The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy.
METHODS In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication.
RESULTS Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040).
CONCLUSIONS Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy.
TRIAL REGISTRATION ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
- 20872016
제1저자 양예원 · 교신저자 임석아, 김태용
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Prognostic impact of AJCC response criteria for neoadjuvant chemotherapy in stage II/III breast cancer patients: breast cancer subtype analyses.BMC Cancer. 2016;16:515.
PubMed IF 4.1 혈액종양내과Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is a standard treatment for stage II/III breast cancer patients, and response to NAC is a useful prognostic marker. Since its introduction, 6-8 cycles of NAC has become the standard regimen to improve the outcome of these patients. The purpose of this study is to evaluate the prognostic impact of the American Joint Committee on Cancer (AJCC) response criteria and this tool's usefulness in four different breast cancer subtypes.
METHODS We conducted a retrospective cohort study of clinical stage II/III breast cancer patients who received NAC of more than 6 cycles. Response after NAC and the clinicopathological factors were reviewed. AJCC response criteria for NAC were adopted from the AJCC Manual, 7th edition: complete response (CR), partial response (PR), and no response (NR).
RESULTS A total of 183 patients were enrolled; 22 (12.0 %), 123 (67.2 %), and 38 (20.8 %) patients showed CR, PR, and NR, respectively. The AJCC response was significantly associated with relapse-free survival (RFS) (P < 0.001), whereas pathologic CR (pCR), the current gold standard for response evaluation for NAC, was not (P = 0.140). AJCC response was a significant prognostic factor for RFS in all four breast cancer subtypes, namely luminal A (P = 0.006), luminal B (P = 0.001), HER-2 enriched (P = 0.039), and triple-negative breast cancer (P = 0.035).
CONCLUSIONS The AJCC response criteria represent a simple and easily reproducible tool for response evaluation of NAC patients and a useful clinical prognostic marker for RFS. These criteria also have a prognostic impact in all four breast cancer subtypes, including luminal A in which pCR has a limited role.
- 20862016
제1저자 윤창환,최영은, 차영륜 · 교신저자 김효수,채인호
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Diabetes-Induced Jagged1 Overexpression in Endothelial Cells Causes Retinal Capillary Regression in a Murine Model of Diabetes Mellitus: Insights Into Diabetic Retinopathy.Circulation. 2016;134(3):233-47.
PubMed IF 41.3 순환기내과Abstract
BACKGROUND Several mechanisms have been proposed to account for diabetes-induced microvasculopathy (DMV). Although Notch signaling was reported to be affected by glucose metabolism in endothelial cells during developmental angiogenesis, it has not been investigated in vascular remodeling of adult capillaries in relation to diabetes mellitus.
METHODS We induced diabetes mellitus in 8-week-old adult mice by intravenously administering streptozotocin. After 6 weeks, we harvested organs, including retina, heart, and skeletal muscle, and evaluated the capillaries with immunofluorescence and confocal microscopy. We modulated endothelial Notch signaling using chemical inhibitors in wild-type mice or transgenic mice, inducing conditional knockout of Jagged1 or Mib1.
RESULTS DMV was characterized by capillary remodeling, regression, and decreased density. Notch ligand Jagged1, but not δ-like ligand 4, was markedly increased in endothelial cells of diabetic mice. Using endothelium-specific Jagged1 knockdown mice, we found that blocking Jagged1 prevented DMV even under diabetic conditions. Furthermore, in the inducible endothelium-specific Jagged1 knockdown mice, blocking Jagged1 even at 4 weeks after the establishment of DMV could reverse it, leading to normalization of retinal vasculature. A search for downstream signals revealed that diabetes mellitus decreased the nuclear localization of Notch1 intracellular domain and reduced the expression of VE-cadherin and N-cadherin in endothelial cells. Chemical Notch inhibition phenocopied DMV in normal mice.
CONCLUSIONS Our findings indicate that diabetes mellitus induces Jagged1 overexpression and suppresses Notch signaling in endothelial cells, leading to DMV in adult mice. We conclude that dysregulated intercellular Notch signaling may be a novel mechanism of DMV.
- 20852016
제1저자 권지혜 · 교신저자 임종필
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Disease Phenotype, Activity and Clinical Course Prediction Based on C-Reactive Protein Levels at Diagnosis in Patients with Crohn's Disease: Results from the CONNECT Study.Gut Liver. 2016;10(4):595-603.
PubMed IF 4.1 소화기내과Abstract
BACKGROUND/AIMS C-reactive protein (CRP) is an easily measured index of disease activity, but its ability to predict clinical course is controversial. We therefore designed a study to determine whether the CRP level at Crohn's disease (CD) diagnosis is a valuable indicator of the disease phenotype, activity, and clinical course.
METHODS We retrospectively analyzed 705 CD patients from 32 institutions. The patients were classified into two groups according to CRP level. The patients' demographic and clinical characteristics and their use of immunosuppressive or biological agents were recorded. Disease location and behavior, hospitalization, and surgery were analyzed.
RESULTS A high CRP was associated with younger age, steroid use, colonic or ileocolonic location, high CD activity index, and active inflammation at colonoscopy (p<0.001). As the disease progressed, patients with high CRP were more likely to exhibit strictures (p=0.027). There were significant differences in the use of 5-aminosalicylic acid, antibiotics, corticosteroids, azathioprine, and infliximab (p<0.001, p<0.001, p<0.001, p<0.001, and p=0.023, respectively). Hospitalization was also more frequent in patients with high CRP.
CONCLUSIONS The CRP level at diagnosis is useful for evaluating the phenotype, activity, and clinical course of CD. Closer follow-up strategies, with early aggressive treatment, could be considered for patients with high CRP.
- 20842016
제1저자 강시혁 · 교신저자 최의근
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Underweight is a risk factor for atrial fibrillation: A nationwide population-based study.Int J Cardiol. 2016;215:449-56.
PubMed IF 3.3 순환기내과Abstract
BACKGROUND Obesity is a well-known risk factor for development of atrial fibrillation (AF). However, the impact of underweight on AF has not been previously recognized. We sought to determine the risk of AF in subjects with underweight in this study.
METHODS We analyzed clinical data from a total of 132,063 individuals with the age of 40years or older who received health care checkups arranged by the national insurance program between 2003 and 2004. Newly diagnosed nonvalvular AF was identified using claim data during a median follow-up duration of 9.0years.
RESULTS The mean body mass index (BMI) of patients was 23.9kg/m(2), and 3,323 individuals (2.5%) were classified as being underweight (BMI <18.5kg/m(2)). During the study period, 3,237 individuals (2.5%) developed AF. There was a U-shaped relationship between BMI and AF occurrence: Each 1.0kg/m(2) increase of BMI above 20kg/m(2) was associated with a 6% increased risk of AF (p<0.001), while each 1.0kg/m(2) lower BMI below 20kg/m(2) was associated with a 13% increased risk of AF (p<0.001) after multivariable adjustment. Underweight was significantly associated with 23% increased risk of AF, while obesity classes I and II were with 26% and 120% increased risk of AF, respectively. Excess risk of AF in the underweight was independent of thyroid disease, chronic lung disease, or history of malignancy, and was not attributable to cigarette smoking, low socioeconomic status, excessive physical activity, or heavy alcohol consumption.
CONCLUSION BMI has a U-shaped relationship with the risk of AF. Underweight was an independent risk factor for AF independent of confounding factors such as chronic lung disease and malignancy. These findings suggest that underweight is associated with biological effects that contribute to the development of AF.
- 20832016
제1저자 이춘수, 김윤기 · 교신저자 김효수
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Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE-cadherin Phosphorylation.Sci Rep. 2016;6:29393.
PubMed IF 4.9 순환기내과Abstract
The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1α (SDF-1α), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1α)-blocker or Src-inhibitor. Disruption of endothelial cell-to-cell junctions in the immuno-fluorescence images correlated with the actual leakage of the endothelial monolayer in the transwell endothelial permeability assay. In the Miles assay, vascular leakage was observed in the ears into which SDF-1α was injected, and this effect was aggravated by DPP4-inhibitor. In the model of retinopathy of prematurity, DPP4-inhibitor increased not only retinal vascularity but also leakage. Additionally, in the murine diabetic retinopathy model, DPP4-inhibitor increased the phosphorylation of Src and VE-cadherin and aggravated vascular leakage in the retinas. Collectively, DPP4-inhibitor induced vascular leakage by augmenting the SDF-1α/CXCR4/Src/VE-cadherin signaling pathway. These data highlight safety issues associated with the use of DPP4-inhibitors.
- 20822016
제1저자 임우현,채인호 · 교신저자 김효수
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Comparison of dual antiplatelet therapy prescribed as one-pill versus two-pill regimen. A pooled analysis of individual patient data from the three MR-CAPCIS trials.Thromb Haemost. 2016;116(1):78-86.
PubMed IF 5.2 순환기내과Abstract
Fixed-dose combination (FDC) drugs can simplify the medication regimen and potentially improve adherence. However, evidence is lacking about the efficacy and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the three independent MR-CAPCIS trials were pooled and analysed. In those trials, subjects who had been treated with either dual antiplatelet therapy (DAPT) or aspirin alone after drug-eluting stent (DES) implantation were randomly assigned to one-pill or to two-pill DAPT group. Platelet reactivity was measured with VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks after treatment. In the present study, primary efficacy endpoint was changes in platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965 subjects were analysed. In prior clopidogrel and aspirin users, PRU was well maintained regardless of switching to either one-pill or two-pill DAPT (ΔPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7 in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between them (p=0.499). The incidence of high on-treatment platelet reactivity at eight weeks, defined as PRU≥235 in Western people, was 34.8 % in one-pill DAPT group and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU ≥275 in Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high platelet reactivity on clopidogrel were female gender, increasing age, and diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT showed similar efficacy to two-pill DAPT in terms of platelet reactivity in patients receiving DES in Korea.
- 20812016
제1저자 박진균 · 교신저자 이은봉
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Survival rates of cancer patients with and without rheumatic disease: a retrospective cohort analysis.BMC Cancer. 2016;16:381.
PubMed IF 4.1 류마티스내과Abstract
BACKGROUND To compare the outcomes of gastric, colon, lung, and breast cancer patients with and without rheumatic diseases (RD).
METHODS This retrospective study compared the cancer survival rates of a cohort of 122 cancer patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), or systemic sclerosis with that of a cohort of 366 age-, sex-, and, cancer type-matched patients without RD who received medical care from 2000 to 2014. Staging, comorbidities, and functional status were ascertained. Survival was compared using the Kaplan-Meier method. Relative risk of death was estimated as a hazard ratio (HR) using Cox regression analysis.
RESULTS The mean age of the RD patients at the time of cancer diagnosis was 58.7 ± 11.5 years. The overall survival rate of gastric cancer patients did not differ between the cohorts. The survival of lung or breast cancer was worse in patients with RA or DM/PM than in those without RD (all, p < 0.05). After adjusting for cancer stage, comorbidity index, performance status and age at the time of cancer diagnosis (as well as interstitial lung disease for lung cancer group), the mortality rate among lung cancer patients with RA was significantly higher (HR, 1.81; 95 % CI, 1.03-3.18) than that of lung cancer patients without RD, whereas SSc was associated with decreased mortality of lung cancer (HR, 0.16; 95 % CI, 0.04-0.58). DM/PM were associated with increased mortality of breast cancer patients (HR, 297.39; 95 % CI, 4.24-20842.33).
CONCLUSIONS RA and DM/PM seemed to be associated with a higher mortality in patients with lung or breast cancers, whereas SSc seemed to be associated with decreased mortality in patients with lung cancer. It is warranted to explore the survival effect of tailored cancer treatments according to specific RD.
- 20802016
제1저자 한재준 · 교신저자 김동완
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Change in PD-L1 Expression After Acquiring Resistance to Gefitinib in EGFR-Mutant Non-Small-Cell Lung Cancer.Clin Lung Cancer. 2016;17(4):263-270.e2.
PubMed IF 3.9 혈액종양내과Abstract
INTRODUCTION Therapies targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) have been successful in a subset of patients with non-small-cell lung cancer (NSCLC). PD-L1 expression in tumor tissues has been suggested as a predictive and prognostic marker. We examined the change in PD-L1 expression after gefitinib in patients with EGFR-mutant NSCLC.
MATERIALS AND METHODS Paired tumor tissues were collected before and after gefitinib from 18 patients. PD-L1 expression on the tumor and immune cells was defined by the H-score of immunohistochemical staining (range, 0-300). The correlations between the change in PD-L1 expression and clinicopathologic characteristics were analyzed.
RESULTS PD-L1 expression on tumor cells showed an increase in the median H-score from 25 to 40 (P = .067). Of the 18 patients, 7 (38.9%) had a marked increase in the median H-score (range, 80-180; group A) and 11 (61.1%) had no change in the median H-score (0 for both scores; group B). In groups A and B, the median progression-free survival for gefitinib was 13 and 12 months (P = .594), and the median overall survival was "not reached" and 38 months (P = .073), respectively. MET positivity by immunohistochemistry in biopsies after gefitinib therapy was significantly associated with group A (P = .028). The PD-L1 H-score by immunohistochemistry, but not by tumor cells, showed correlations with other immune cells; FOXP3(+) expression in biopsies before gefitinib use, and PD-1(+) and CD3(+) in biopsies after gefitinib therapy, respectively.
CONCLUSION PD-L1 expression in tumor cells markedly increased in a subset of patients after gefitinib treatment. Thus, rebiopsy should be considered when using PD-L1 expression as a biomarker.
- 20792016
제1저자 최연악 · 교신저자 오도연
, , , , , , , , , ,
Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study.Cancer Res Treat. 2016;48(3):1045-55.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC.
MATERIALS AND METHODS Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.
RESULTS Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group.
CONCLUSION In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.
- 20782016
제1저자 남아롱, 김지원 · 교신저자 오도연
, , , , , , , , , , ,
Src as a Therapeutic Target in Biliary Tract Cancer.Mol Cancer Ther. 2016;15(7):1515-24.
PubMed IF 6.9 혈액종양내과Abstract
Src, a nonreceptor tyrosine kinase, is involved in a number of cancer-related signaling pathways and aberrantly activated in biliary tract cancer (BTC). This study aimed to elucidate the potential role of Src as a therapeutic target in BTC. We tested bosutinib, an orally active c-Src/Abl kinase inhibitor, alone or in combination with cytotoxic agents using 9 human BTC cell lines: SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079, SNU-1196, HuCCT1, TFK-1, and EGI-1. Of these, SNU-308 and SNU-478 were relatively sensitive to bosutinib. Bosutinib abrogated phosphorylation of Src and its downstream molecules, and significantly increased G1 cell-cycle arrest and apoptosis. Bosutinib significantly inhibited cell migration and invasion and decreased epithelial-mesenchymal transition markers. Bosutinib combined with gemcitabine or cisplatin showed synergistic antiproliferative and antimigratory effects. In addition, this combination further inhibited phosphorylation of Src and its downstream molecules and decreased epithelial-mesenchymal transition marker expression compared with bosutinib alone. We established a SNU-478 xenograft model for in vivo experiments, because SNU-478 was more tumorigenic than SNU-308. Bosutinib combined with gemcitabine or cisplatin showed significantly more potent antitumor effects than bosutinib alone. Bosutinib combined with gemcitabine further decreased Ki-67 expression and Src phosphorylation, and further increased TUNEL expression. Our data suggest that Src might be a potential therapeutic target in BTC. Bosutinib demonstrated promising antitumor activity alone or in combination with gemcitabine or cisplatin in BTC cells, which supports further clinical development in patients with advanced BTC. Mol Cancer Ther; 15(7); 1515-24. ©2016 AACR.
- 20772016
제1저자 서경진, 유한석 · 교신저자 임석아, 이경훈
, , , , , , , , , , , , ,
Loss of ataxia-telangiectasia-mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer.Breast Cancer Res Treat. 2016;158(2):233-41.
PubMed IF 3.3 혈액종양내과Abstract
We investigated the correlation of ataxia-telangiectasia-mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. ATM loss was observed in 126/407 evaluable cases (31.0 %), and was significantly associated with larger tumor size, lymph node metastasis, higher tumor grade, and ER- and/or PR-negative status. ATM loss was also associated with significantly lower disease-free survival rates than those in patients with intact ATM (5-year disease-free survival rate 81.2 vs. 90.7 %, p = 0.015). In multivariate analysis, ATM loss combined with abnormal p53 expression was an independent predictor of shorter disease-free survival [hazard ratio (HR) 3.48; 95 % confidence interval (CI), 1.48-8.17, p = 0.004]. A tendency towards a poorer prognosis was observed for tumoral ATM loss alone, although statistical significance was not reached (HR 1.74; 95 % CI 0.95-3.20; p = 0.075). In subgroup analysis, ATM loss was associated with shorter disease-free survival in patients who did not receive adjuvant anthracycline chemotherapy (5-year disease-free survival rate 92.7 % in intact ATM group vs. 68.1 % in ATM loss group, p = 0.002), but this poor prognosis was overcome in patients who did (5-year disease-free survival rate 89.8 vs. 84.4 %, p = 0.243), suggesting more benefit from anthracycline-based chemotherapy. Tumors with loss of ATM expression have a poor prognosis and their prognoses are dependent on the use of adjuvant anthracycline. ATM loss might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy.
- 20762016
제1저자 서경진 · 교신저자 김범석
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Serum Neuron-Specific Enolase Levels Predict the Efficacy of First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations.Clin Lung Cancer. 2016;17(4):245-252.e1.
PubMed IF 3.9 혈액종양내과Abstract
OBJECTIVES Our study aimed to determine the predictive and prognostic values of the serum neuron-specific enolase (NSE) level in patients who had non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and who had been treated with EGFR-tyrosine kinase inhibitors (TKIs).
MATERIALS AND METHODS We retrospectively analyzed 151 patients who had NSCLC harboring EGFR mutations and had received either gefitinib or erlotinib as first-line treatment between 2005 and 2014. The serum NSE level was measured before initiation of EGFR-TKI treatment.
RESULTS Of the 151 patients, 92 (60.9%) had elevated NSE levels (> 16.3 ng/mL). Patients with elevated NSE levels showed significantly shorter progression-free survival (PFS) after EGFR-TKI treatment than those with normal NSE levels (median PFS, 10.5 months vs. 15.4 months; P = .034). Multivariate analysis demonstrated that elevated NSE levels (hazard ratio [HR], 1.656; P = .017), CNS metastasis at diagnosis (HR, 1.567; P = .037), and male gender (HR, 1.840; P = .005) were independent predictive factors for short PFS. A significant difference in overall survival (OS) was observed between patient groups with elevated and normal NSE levels (median OS, 17.0 months vs. 29.1 months; P < .001), and serum NSE level remained an independent prognostic factor for OS in multivariate analysis (HR, 2.671; P < .001).
CONCLUSION Patients with elevated serum NSE levels have significantly shorter PFS and OS. The NSE level is both a predictive marker of EGFR-TKI treatment and a prognostic marker in EGFR-mutant NSCLC patients.
- 20752016
제1저자 김희진 · 교신저자 김나영
, , , , , , , , , , , ,
Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?Gastric Cancer. 2016;19(3):798-807.
PubMed IF 6.1 소화기내과Abstract
BACKGROUND A large-scale study was performed to identify the risk factors for developing synchronous and metachronous colorectal cancer (CRC) in gastric cancer (GC) patients, including microsatellite instability (MSI) and p53 overexpression.
METHODS A total of 1041 GC patients who underwent endoscopic resection or surgery and underwent colonoscopy simultaneously or during surveillance for GC were consecutively enrolled. Clinicopathologic characteristics, MSI, and p53 overexpression were compared between the GC patients with and those without synchronous and metachronous CRC.
RESULTS Of the 1041 patients, CRCs were detected in 67 (6.4 %) patients with GC. Forty-six (4.4 %) had synchronous CRC and 21 (2.0 %) had metachronous CRC. Univariate analysis indicated that age ≥63 years (P < 0.001), male sex (P = 0.005), and p53 overexpression (P = 0.040) were significantly associated with a higher incidence of CRC. However, body mass index, smoking, tumor location, tumor multiplicity, tumor histology, TNM stage, and MSI were not significantly associated with the incidence of CRC. Age ≥63 years (OR: 5.881; 95 % CI: 3.083-11.221; P < 0.001) and male sex (OR: 2.933; 95 % CI: 1.307-6.584; P = 0.009) were risk factors for CRC in GC patients according to multivariate analysis.
CONCLUSIONS GC patients who are male and/or ≥63 years old are recommended to receive colonoscopy to detect CRC. MSI and p53 overexpression were not useful molecular markers for predicting CRC in GC.
- 20742016
제1저자 김경민 · 교신저자 임수
, ,
Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia.Korean J Intern Med. 2016;31(4):643-50.
PubMed IF 2.2 내분비대사내과Abstract
Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective.
- 20732016
제1저자 이승아, 차명진 · 교신저자 오세일
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Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing.Heart Vessels. 2016;31(7):1131-9.
PubMed IF 1.5 순환기내과Abstract
Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient's 12-lead ECG. During a mean 15.6 years (range 3.3-30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22-2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15-2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03-1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01-1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.
- 20722016
제1저자 기모란 · 교신저자 정숙향
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Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study.Liver Int. 2016;36(7):1067-73.
PubMed IF 6.2 소화기내과Abstract
BACKGROUND & AIMS The population-based epidemiology of Budd-Chiari syndrome (BCS), a rare disease of hepatic venous outflow obstruction, is largely unknown. This study aimed to elucidate the nationwide population-based incidence, prevalence, complications, case fatalities and direct medical cost of BCS in South Korea from 2009 to 2013.
METHODS Using two large data sources, the Health Insurance Review and Assessment Service Claims database and Rare Intractable Disease registration program database in Korea, we identified all patients with BCS who were registered under International Classification of Diseases 10 (code I82.0). The age- and sex-adjusted incidence and prevalence of BCS were calculated with analysis of complications and direct medical costs.
RESULTS A total of 424 patients with BCS were identified in 2009-2013, with a female-to-male ratio of 1.8 and a median age of 51 years old. The average age- and sex-adjusted incidence from 2011 to 2013 was 0.87 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 5.29 per million population. Among them, 10.3% accompanied liver cancer and 3.3% underwent liver transplantation. Annual case-fatality rate was 2.8%. Direct medical costs excluding uninsured services for BCS increased by year from 385 720 USD in 2009 to 765 983 USD in 2013.
CONCLUSIONS This is the first population-based study on the epidemiology of BCS in an Asian country, which presented a higher prevalence than in Western studies. It suggests early diagnosis or improved prognosis of BCS in recent years, and clinical features of BCS that differ by geography.
- 20712016
제1저자 박주경 · 교신저자 류지곤
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Clinical Outcomes of Endoscopic Ultrasonography-Guided Pancreatic Cyst Ablation.Pancreas. 2016;45(6):889-94.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES Endoscopic ultrasonography-guided ethanol ablation therapy for pancreatic cystic lesions is a minimally invasive treatment but still is an experimental therapy. The aims were to investigate the safety and efficacy of endoscopic ultrasonography-guided ethanol ablation therapy.
METHODS The inclusion criteria were the following: clinically indeterminate pancreatic cystic lesions in radiologic imaging studies, 2 to 5 cm unilocular or oligolocular cysts without communication to main pancreatic duct, and patients with high-risk operation.
RESULTS There were 91 study patients with median follow-up of 40 months. The response rate was as follows: complete resolution, 41 (45%); partial resolution, 37; and persistent cysts, 13. Pancreatic cystic lesions were categorized based on cystic fluid analysis: 9 intraductal papillary mucinous neoplasms (IPMNs), 12 mucinous cystic neoplasms, 33 serous cystic neoplasms, and 28 uncategorized cysts. The success rate was significantly different according to cystic fluid analysis (serous cystic neoplasm, 58%; mucinous cystic neoplasm, 50%; IPMN, 11%; uncategorized cysts, 39%; P < 0.0001). There were 3 patients with mild pancreatitis after the treatment.
CONCLUSIONS Endoscopic ultrasonography-guided ethanol ablation therapy seems to be a safe treatment modality. However, it was only effective in 11% of IPMNs. Therefore, the clinical application should be very limited for certain patients who could not tolerate the surgical treatment.
- 20702016
제1저자 박완범,조주연 · 교신저자 김홍빈,송상훈
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Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.Int J Antimicrob Agents. 2016;48(1):106-110.
PubMed IF 5 감염내과Abstract
Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy.
- 20692016
제1저자 박흥우 · 교신저자 박흥우
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Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations.Eur Respir J. 2016;48(1):104-14.
PubMed IF 23.8 알레르기내과Abstract
Methacholine bronchial provocation test provides the concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 s (FEV1) from baseline (PC20). The dose-response slope (DRS), and other continuous indices of responsiveness (CIR; the percentage decline from the post-diluent baseline FEV1 after the last dose of methacholine), and per cent recovery index (PRI; the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation) are alternative measures. The clinical relevance of these indices in predicting acute asthma exacerbations has not been fully evaluated.In two prospective cohorts of childhood and elderly asthmatics, baseline PC20, DRS, CIR and PRI were measured and evaluated as predictors of acute asthma exacerbations.We found that PRI was significantly related to the presence of asthma exacerbations during the first year of follow-up in both cohorts of childhood (p=0.025) and elderly asthmatics (p=0.003). In addition, PRI showed a significant association with the total number of steroid bursts during 4.3 years of follow-up in the cohort of childhood asthmatics (p=0.04).We demonstrated that PRI, an index of reversibility following methacholine-induced bronchoconstriction, was a good clinical predictor of acute exacerbations of asthma in both childhood and elderly asthmatics.
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