SCI 발표논문

2017년 269편

2692017

제1저자 Jian Wei Xu · 교신저자 진호준

Jian Wei Xu, Lee ES, Chin HJ
Darbepoetin-α ameliorates diabetes-induced mesangial cell damage In Vitro and Vivo.
Int J Clin Exp Med. 2017;10(10):Epub ahead of print.

IF 1.069 신장내과
2682017

제1저자 E. Van Cutsem, 방영주 · 교신저자 E. Van Cutsem

E. Van Cutsem, Y.-J. Bang, W. Mansoor, R. D. Petty, Y. Chao, D. Cunningham, D. R. Ferry, N. R. Smith, P. Frewer, J. Ratnayake, P. K. Stockman, E. Kilgour, D. Landers.
A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification.
Ann Oncol. 2017;28(6):1316-1324.

IF 9.269 혈액종양내과
2672017

제1저자 옥찬영 · 교신저자 김범석

Ock CY, Kim S, Keam B, Kim S, Ahn YO, Chung EJ, Kim JH, Kim TM, Kwon SK, Jeon YK, Jung KC, Kim DW, Wu HG, Sung MW, Heo DS.
Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma.
Oncotarget. 2017;8(58):97920-97927..

IF 5.168 혈액종양내과
2662017

제1저자 김령, 김미화 · 교신저자 오도연

, , , , , ,
Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer.
Cancer Lett. 2017;411:162-170.

Abstract
There are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, PI3KCA. BKM120 inhibited the colony-forming ability and migration of BTC cells carrying wild-type (WT) PI3KCA and either mutant (MT) or WT K-Ras, but not of cells carrying mutations in both genes. In K-Ras-WT cells, BKM120 decreased the phosphorylation of Akt, its downstream effector kinase p70S6K, and the translational repressor 4E-BP1. Interestingly, BKM120 did not induce cell cycle arrest or suppress PI3K signaling via restoration of p-4E-BP1 in cells with PIK3CA and K-Ras double mutations. Notably, the resistance of dual K-Ras/PI3KCA-mutant cells to BKM120 was overcome by treatment with a combination of BKM120 and MEK162. Our findings thus support the clinical development of BKM120 monotherapy or BKM120/MEK162 combination therapy for the treatment of BTC.
PubMed IF 11.8 혈액종양내과
2652017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , ,
Clinical Outcomes According to Fractional Flow Reserve or Instantaneous Wave-Free Ratio in Deferred Lesions.
JACC Cardiovasc Interv. 2017;10(24):2502-2510.

Abstract
OBJECTIVES The authors investigated 2-year clinical outcomes according to fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) values in deferred lesions.
BACKGROUND Invasive physiological indices such as FFR or iFR are used in clinical practice to select ischemia-causing stenosis and to guide the treatment strategy for patients with coronary artery disease.
METHODS From the 3V FFR-FRIENDS (3-Vessel Fractional Flow Reserve for the Assessment of Total Stenosis Burden and Its Clinical Impact in Patients With Coronary Artery Disease) study, 821 deferred lesions (n = 374) with both FFR and iFR available were included in this study. The primary outcome was major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years. The lesions were classified according to FFR and iFR cutpoints into concordant normal (Group 1: FFR >0.80 and iFR >0.89), high FFR and low iFR (Group 2: FFR >0.80 and iFR ≤0.89), low FFR and high iFR (Group 3: FFR ≤0.80 and iFR >0.89), and concordant abnormal (Group 4: FFR ≤0.80 and iFR ≤0.89).
RESULTS Deferred lesions with low FFR (≤0.80) or low iFR (≤0.89) showed significantly higher rates of 2-year MACE, compared with high FFR (>0.80) or high iFR (>0.89), respectively (7.2% in low FFR vs. 2.4% in high FFR; p < 0.001; 8.1% in low iFR vs. 2.4% in high iFR; p < 0.001). Both FFR and iFR showed significant association with occurrence of MACE as continuous values (hazard ratio [HR] of FFR: 0.570, 95% confidence interval [CI]: 0.337 to 0.963; p < 0.001; HR of iFR: 0.350, 95% CI: 0.217 to 0.567; p < 0.001). When comparing the discriminant ability between FFR and iFR, the c-index was comparable between FFR and iFR (c-index 0.677 vs. 0.685; p = 0.857). Among 4 groups classified according to FFR and iFR levels, only Group 4 with concordant abnormal results showed significantly higher risk of MACE, compared with group 1 (HR: 7.708, 95% CI: 2.621 to 22.667; p < 0.001).
CONCLUSIONS Both FFR and iFR showed significant association with future risk of MACE in deferred lesions. The discordant results between FFR and iFR were not associated with the increased risk of MACE. The risk of MACE was significantly increased only in lesions with abnormal results of both FFR and iFR.
PubMed IF 12.7 순환기내과
2642017

제1저자 이소령 · 교신저자 최의근

, , , , ,
Temporal trends of antithrombotic therapy for stroke prevention in Korean patients with non-valvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants: A nationwide population-based study.
PLoS One. 2017;12(12):e0189495.

Abstract
BACKGROUND Following their introduction, the non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly prescribed in Asia for stroke prevention in patients with non-valvular atrial fibrillation (AF). Few contemporary data are available on temporal trends in antithrombotic therapy use in Asian countries, in the era of NOACs.
METHODS AND RESULTS Using the National Health Insurance Service database of the entire Korean adult AF population, the use of aspirin, vitamin K antagonist, and NOACs between 2008 and 2015 were analyzed (n = 276,246 in 2015). Most of the included cohort had CHA2DS2-VASc score ≥ 2 (78.2% in 2008 and 83.2% in 2015), yet approximately 17% were prescribed no antithrombotic therapy throughout the study period. Aspirin prescription consistently decreased (from 48.2% to 31.5%) over time, while OAC prescription significantly increased from 34.7% to 50.6%. NOAC prescriptions accounted for 50% of total OAC prescription in 2015. Similar trends in antithrombotic therapy were found both in men and in women, but women were more likely to be undertreated with OAC. Female gender, presence of vascular disease and prior intracranial hemorrhage were associated with OAC underuse.
CONCLUSIONS Between 2008 and 2015, a greater proportion of AF patients received OAC treatment with increasing NOAC prescription trends in the recent 3 years. A substantial proportion (approx. 50%) of Korean patients with AF still remain undertreated.
PubMed IF 2.8 순환기내과
2632017

제1저자 이종식 · 교신저자 임재준

, , , , , ,
Implication of species change of Nontuberculous Mycobacteria during or after treatment.
BMC Pulm Med. 2017;17(1):213.

Abstract
BACKGROUND Co-existence or subsequent isolation of multiple nontuberculous mycobacteria (NTM) species in same patient has been reported. However, clinical significance of these observations is unclear. The aim of this study was to determine clinical implications of changes of NTM species during or after treatment in patients with NTM lung disease.
METHODS Patients with NTM lung disease, who experienced changes of NTM species during treatment or within 2 years of treatment completion between January 1, 2009 and December 31, 2015, were included in the analysis. Demographic, clinical, microbiological, and radiographic data were reviewed and analyzed.
RESULTS During the study period, 473 patients were newly diagnosed with NTM lung disease. Treatment was started in 164 patients (34.6%). Among these 164 patients, 16 experienced changes of NTM species during or within 2 years of treatment completion. Seven showed changes from M. avium complex (MAC) to M. abscessus subspecies abscessus (MAA) and five patients displayed changes from M. abscessus subspecies massiliense (MAM) to MAC. With isolation of new NTM species, 6 out of 7 patients with change from MAC to MAA reported worsening of symptoms, whereas none of the five patients with change from MAM to MAC reported worsening of symptoms. All MAA isolated during or after treatment for MAC lung diseases showed inducible resistance to clarithromycin.
CONCLUSIONS Change of NTM species may occur during or after treatment for NTM lung disease. Especially, changes from MAC to MAA is accompanied by symptomatic and radiographic worsening as well as inducible resistance to clarithromycin.
PubMed IF 3.1 호흡기내과
2622017

제1저자 이창훈, 최성미 · 교신저자 김덕겸

, , , , , , , ,
Inhaled bronchodilators and acute myocardial infarction: a nested case-control study.
Sci Rep. 2017;7(1):17915.

Abstract
We investigated the association between the use of inhaled bronchodilators and the risk of AMI. A nested case-control study using the nationwide insurance claims database was conducted. Overall, 11,054 AMI cases and 47,815 matched (up to 1:5) controls were identified from 1,036,119 subjects without acute major cardiovascular events in the past year. Long-acting and short-acting β-agonists (LABAs and SABAs) were associated with increase in the risk of AMI, although an inhaled corticosteroid combined with a long-acting β-agonist was not. Long-acting muscarinic antagonists (LAMAs) in a dry powder inhaler (DPI) were significantly associated with reduced risk of AMI, while LAMAs in a soft mist inhaler (SMI) didn't decrease the risk of it. In hypertensive or diabetic patients, LAMAs in a DPI were associated with reduced risk of AMI, but LABAs were associated with increased risk. Among the β-blocker users, the reduction of AMI risk by LAMAs was the most significant. In conclusions, inhaled β-agonists were associated with increase in the risk of AMI, while LABAs accompanied by ICSs were not associated with increase in the risk of AMI. LAMAs in a DPI use were associated with lower risk of AMI.
PubMed IF 4.9 호흡기내과
2612017

제1저자 장영, 최원혁, 신동현 · 교신저자 이정훈

, , , , , , , , , , , , , , , , ,
Nucleos(t)ide Analogue Treatment for Patients With Hepatitis B Virus (HBV) e Antigen-Positive Chronic HBV Genotype C Infection: A Nationwide, Multicenter, Retrospective Study.
J Infect Dis. 2017;216(11):1407-1414.

Abstract
BACKGROUND Antiviral treatment for hepatitis B virus (HBV) e antigen (HBeAg)-positive chronic HBV infection is still controversial. We assessed whether antiviral treatment reduces the risk of liver disease progression in these patients.
METHODS This study included consecutive patients in 8 large-volume hospitals in Korea who tested positive for HBeAg and had an HBV DNA level of >20000 IU/mL, an alanine aminotransferase (ALT) level of <40 IU/L, and no evidence of cirrhosis. The primary end point was the development of hepatocellular carcinoma (HCC), and the secondary end point was the development of cirrhosis.
RESULTS A total of 484 patients were included: 87 were in the antiviral treatment group, and 397 were in the control group. Baseline liver function was significantly more favorable for the control group. After matching for propensity score to overcome those differences, the antiviral treatment group had a significantly reduced risk for HCC (hazard ratio [HR], 0.234; log-rank P = .046) and cirrhosis (HR, 0.235; log-rank P = .015), compared with the control group. After balancing the baseline characteristics by using inverse probability weighting, antiviral therapy significantly decreased the risk of HCC (HR, 0.189; log-rank P = .004) and cirrhosis (HR, 0.347; log-rank P = .036).
CONCLUSION Antiviral therapy for patients with HBeAg-positive chronic HBV infection and have a high HBV load reduces the risk of HCC, even if the ALT level is below the upper limit of normal.
PubMed IF 4.1 소화기내과
2602017

제1저자 서정원 · 교신저자 김효수

, , , , , , , , , , , , , ,
The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.
Int Heart J. 2017;58(6):853-860.

Abstract
It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.
PubMed IF 1.4 순환기내과
2592017

제1저자 최윤진, 박영수 · 교신저자 김나영

, , , , , ,
Gender differences in ghrelin, nociception genes, psychological factors and quality of life in functional dyspepsia.
World J Gastroenterol. 2017;23(45):8053-8061.

Abstract
AIM to evaluate gender differences in the aspect of ghrelin, nociception-related genes and psychological aspects and the quality of life (QoL) in Korean functional dyspepsia (FD) patients.
METHODS Total of 191 persons were prospectively enrolled between March 2013 and May 2016 in Seoul National Bundang Hospital, and classified into control and FD group based on ROME III criteria. Questionnaire included assessment for dyspepsia symptoms, QoL and anxiety or depression. Preproghrelin and nociception genes in the gastric mucosa and plasma acyl/des-acyl ghrelin were measured.
RESULTS Lower level of plasma acyl ghrelin in FD patients compared to control was significant only in male (15.9 fmol/mL vs 10.4 fmol/mL, P = 0.017). Significantly higher mRNA expressions of nerve growth factor and transient receptor potential vanilloid receptor 1 were observed in male (P = 0.002 and P = 0.014, respectively) than in female. In contrast, female FD patients had a higher anxiety and depression score than male FD (P = 0.029), and anxiety score was correlated with epigastric pain only in female FD patients (female: Spearman rho = 0.420, P = 0.037). The impairment of overall QoL was more prominent in female FD patients than male patients (5.4 ± 0.3 vs 6.5 ± 0.3, P = 0.020).
CONCLUSION Gender differences of ghrelin and nociception-related genes in male and psychological factors in female underlie FD symptoms. More careful assessment of psychological or emotional status is required particularly for the female FD patients.
PubMed IF 7.7 소화기내과
2582017

제1저자 이상훈 · 교신저자 박종선

, , , , , , , , , , , , , , , , , , ,
Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study.
Respir Res. 2017;18(1):204.

Abstract
BACKGROUND The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea.
METHODS The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC <10%). Factors affecting treatment response were evaluated by multivariate logistic regression analysis.
RESULTS A total of 261 patients with iNSIP were enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid treatment was performed in 86 patients. The treatment group showed a significant improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume (FEV₁), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p < 0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related with lung function improvement. Sero-positivity ANA was significantly lower in the response group (p = 0.013), compared to that in the non-response group. A shorter duration of respiratory symptoms at diagnosis was significantly associated with a good response to treatment (p = 0.018).
CONCLUSION Treatment with corticosteroids and/or immunosuppressants improved lung function in iNSIP patients, which was more pronounced in sero-negative ANA and shorter symptom duration patients. These findings suggest that early treatment should be considered in iNSIP patients, even in an early disease stage.
PubMed IF 5.7 호흡기내과
2572017

제1저자 정정화 · 교신저자 김진욱

, , , , , , ,
Development of a nomogram for screening of hepatitis B virus-associated hepatocellular carcinoma.
Oncotarget. 2017;8(63):106499-106510.

Abstract
Current strategy of hepatocellular carcinoma (HCC) surveillance evaluates individual risks of HCC for defining candidates for surveillance, but estimated risks are not utilized for clinical decision-making during actual screening. We sought to determine whether consideration of individual risks improve the performance of ultrasound (US)-based HCC screening in a real-world chronic hepatitis B (CHB) cohort. This single center retrospective cohort study analyzed 27,722 screening US tests from 4,175 consecutive CHB patients. Logistic regression analysis was performed to identify independent parameters predicting presence of HCC. A nomogram was built based on the independent predictors of HCC and compared with US-only screening by receiver operating characteristics analysis. The cost-effectiveness of the nomogram was assessed by decision curve analysis. HCC developed in 222 patients with the incidence of 0.769 per 1000 person-year during the median follow-up of 63 months. Age, sex, presence of cirrhosis, serum alpha-fetoprotein (AFP) levels and positive US test results were independent predictors of HCC presence. A nomogram based on these predictors showed higher C-statistics compared to US-only screening (0.960 vs. 0.731 and 0.935 vs. 0.691 for derivation and validation cohort, respectively; p < 0.001). Decision curve analysis showed higher net benefit of the HCC nomogram-guided screening model compared to US-only screening in the risk threshold range between 0 and 0.3. A nomogram composed of age, sex, presence of cirrhosis, serum AFP levels and US findings better predicted the presence of HCC compared to US-only screening in CHB on surveillance.
PubMed IF 5.168 소화기내과
2562017

제1저자 이지은 · 교신저자 김경민

, , , , , , , , , ,
Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: A cross-sectional observation.
Bone. 2017;105:269-275.

Abstract
Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1-L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.
PubMed IF 3.9 내분비대사내과
2552017

제1저자 송영신, 임정아 · 교신저자 박영주

, , , , , , , , , ,
Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer.
Eur J Endocrinol. 2017;177(6):465-473.

Abstract
OBJECTIVE Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer (FTC) over time have not been reported. Moreover, the prognostic effects of RAS and TERT promoter mutations in FTC have not been clearly elucidated. We investigated changes in the clinicopathological characteristics of patients with FTC over four decades, as well as the clinical significance of genetic mutations of FTC.
DESIGN AND METHODS This retrospective study included 690 patients with FTC who underwent thyroidectomy between 1973 and 2015 at the Seoul National University Hospital. In 134 samples, genetic tests for N/H/KRAS and TERT promoter mutations and PAX8/PPARγ rearrangement were performed.
RESULTS The age at diagnosis has increased (P < 0.001) in recent decades and extrathyroidal extension of the tumor has become less common (P = 0.033). Other clinicopathological characteristics and prognosis of FTC have not significantly changed. The prevalence of RAS mutations decreased (P = 0.042) over time, whereas that of TERT promoter mutations remained stable. RAS mutations were associated with distant metastasis and persistent disease, and TERT promoter mutations were associated with distant metastasis, advanced TNM stage, recurrence and disease-specific mortality. FTC patients with coexistent RAS and TERT promoter mutations showed a higher recurrence risk than those with only one mutation.
CONCLUSIONS The age at diagnosis of FTC and the frequency of extrathyroidal extension have changed over four decades. Moreover, the prevalence of RAS mutations decreased. RAS and TERT promoter mutations may be associated with poor clinical outcomes in FTC, especially when the two mutations coexist.
PubMed IF 6.7 내분비대사내과
2542017

제1저자 홍아람, 김정희 · 교신저자 김상완

, , , , , , , , ,
Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice.
Eur J Endocrinol. 2017;177(6):475-483.

Abstract
OBJECTIVE Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years.
DESIGN AND METHODS This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines.
RESULTS The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study.
CONCLUSIONS We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.
PubMed IF 6.7 내분비대사내과
2532017

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , , ,
Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017;18(12):1637-1651.

Abstract
BACKGROUND Olaparib combined with paclitaxel has previously shown a significant improvement in overall survival versus placebo plus paclitaxel as second-line therapy in a phase 2 study in Asian patients with advanced gastric cancer, especially in those with ataxia-telangiectasia mutated protein (ATM)-negative tumours. Here, we report the primary efficacy and safety analyses from a subsequent phase 3 trial.
METHODS This double-blind, randomised, placebo-controlled, phase 3 study (GOLD) recruited Asian patients aged 18 years or older (≥20 years if Japanese) with advanced gastric cancer that had progressed following, or during, first-line chemotherapy. Patients were randomly assigned (1:1) to receive oral olaparib (100 mg twice daily) plus paclitaxel (80 mg/m² intravenously) or matching placebo plus paclitaxel. Randomisation was done through an interactive voice response system and no stratification factors were used. Patients and investigators were masked to treatment allocation. Two co-primary populations were assessed: the overall population of all patients and patients whose tumours were ATM-negative (identified after randomisation, before the data cutoff date, March 28, 2016). The primary endpoint in both populations was overall survival (defined as the time from the date of randomisation until death from any cause before data cutoff); a significant difference was defined as p<0·025. Efficacy was assessed in the intention-to-treat populations and safety in patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT01924533 (study ID, D081BC00004), and is ongoing but no longer recruiting participants.
FINDINGS Between Sept 3, 2013, and March 28, 2016, 643 patients were enrolled from 58 study sites in hospitals and medical centres in China, Japan, South Korea, and Taiwan. 525 eligible patients were randomly assigned: 263 to receive olaparib plus paclitaxel and 262 to receive placebo plus paclitaxel. 94 patients were determined to have ATM-negative tumours before unmasking for the primary analysis (48 in the olaparib plus paclitaxel group and 46 in the placebo plus paclitaxel group). Overall survival did not differ between treatment groups in the overall patient population (median overall survival 8·8 months [95% CI 7·4-9·6] in the olaparib group vs 6·9 months [6·3-7·9] in the placebo group; HR 0·79 [97·5% CI 0·63-1·00]; p=0·026) or in the ATM-negative population (12·0 months [7·8-18·1] vs 10·0 months [6·4-13·3]; 0·73 [0·40-1·34]; p=0·25). In the overall patient population, the most common grade 3 or worse adverse events in the olaparib plus paclitaxel group were neutropenia (78 [30%] of 262 patients), leucopenia (42 [16%]), and decreased neutrophil count (40 [15%]); in the placebo plus paclitaxel group, they were neutropenia (59 [23%] of 259 patients), leucopenia (27 [10%]), and decreased white blood cell count (21 [8%]). Adverse events with an outcome of death causally related to study treatment (according to investigator assessment) were reported in two patients: liver injury in one patient (<1%) in the olaparib plus paclitaxel group and cardiac failure in one patient (<1%) in the placebo plus paclitaxel group.
INTERPRETATION The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in the overall or ATM-negative population of Asian patients with advanced gastric cancer. The study generated informative efficacy and safety data regarding the use of olaparib in combination with a chemotherapeutic agent and provides a foundation for future studies in this difficult-to-treat patient population.
FUNDING AstraZeneca.
PubMed IF 33.7 혈액종양내과
2522017

제1저자 장경민 · 교신저자 김학령

, , , , , , , , ,
Additional Value of Brachial-Ankle Pulse Wave Velocity to Single-Photon Emission Computed Tomography in the Diagnosis of Coronary Artery Disease.
J Atheroscler Thromb. 2017;24(12):1249-1257.

Abstract
AIM The aim of this study was to investigate whether information on arterial stiffness can improve the value of single-photon emission computed tomography (SPECT) in the detection of obstructive coronary artery disease (CAD).
METHODS A total of 233 patients (age: 62.2±10.8 years, 60.3% males) with detected ischemia on SPECT undergoing invasive coronary angiography (ICA) and brachial-ankle pulse wave velocity (baPWV) measurement within a month was retrospectively reviewed.
RESULTS Of the 233 patients, 190 (81.5%) had obstructive CAD (≥50% luminal stenosis). The difference in baPWV according to the presence of obstructive CAD was significant in patients in the mild ischemia group [summed stress score (SSS): 4-8] (1,770±364 cm versus 1,490±328 cm, p＜0.001) but not in the moderate (SSS: 9-13) or severe (SSS: ≥14) ischemia groups (p＞0.05 for each). Receiver operating characteristic curve analyses showed that the diagnostic value of baPWV for obstructive CAD was significant only in patients in the mild ischemia group (area under curve: 0.714; p=0.001) but not in the moderate or severe ischemia groups (p＞0.05 for each). Adding information on baPWV to SPECT results and clinical parameters significantly increased diagnostic accuracy in the detection of obstructive CAD in patients with mild ischemia (integrated discrimination improvement p=0.006) but not in those with moderate or severe ischemia on SPECT (p＞0.05 for each).
CONCLUSIONS The results of this study suggest that baPWV may have additional value to SPECT for the detection of obstructive CAD, especially in patients with mild ischemia on SPECT.
PubMed IF 3.4 순환기내과
2512017

제1저자 박진주 · 교신저자 최동주

, , , , , , , , , , , , , ,
Short and long-term prognostic value of hyponatremia in heart failure with preserved ejection fraction versus reduced ejection fraction: An analysis of the Korean Acute Heart Failure registry.
Int J Cardiol. 2017;248:239-245.

Abstract
BACKGROUND Hyponatremia is a well-known risk factor for worse outcomes in heart failure (HF) patients. The impact of hyponatremia according to the ejection fraction (EF) is unclear. We evaluated the prognostic value of hyponatremia according to HF type.
METHODS AND RESULTS The Korea Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients. Hyponatremia was defined as serum sodium level<135mmol/L at hospital admission. HF with preserved and reduced ejection fraction were defined as an LVEF ≥50% and LVEF ≤40%, respectively. Among 5103 patients with available EF, 2088 (60%) had HFrEF, and 1284 (25%) had HFpEF. There was no difference in serum sodium level between the groups (HFrEF: 137.4±4.7mmol/L vs. HFpEF: 137.5±5.0mmol/L, P=0.710). Hyponatremic patients had higher in-hospital mortality or urgent heart transplantation in all (11.3% vs. 4.5%, P<0.001), in HFrEF (13.1% vs. 4.9%, P<0.001), and in HFpEF (6.0% vs. 1.9%, P<0.001). After adjustment for significant covariates, hyponatremia was associated with 1.5 fold increased risk for 1-year post-discharge death in the HFrEF group (HR, 1.52; 95% CI, 1.24-1.86), but not in the HFpEF group (HR, 1.16; 95% CI, 0.84-1.61). During admission, the sodium status changed in 22% of the patients and the discharge sodium status had greater prognostic value.
CONCLUSIONS Hyponatremia is independent of HF type. Hyponatremia is a significant risk factor for adverse in-hospital outcomes; however its long-term prognostic value is only limited to patients with HFrEF, but not for those with HFpEF.
PubMed IF 3.3 순환기내과
2502017

제1저자 강시혁 · 교신저자 최동주

, , , , , , ,
Risk of stroke in congestive heart failure with and without atrial fibrillation.
Int J Cardiol. 2017;248:182-187.

Abstract
BACKGROUND Heart failure has been associated with an increased risk for ischemic stroke. This study estimated the risk of stroke and thromboembolism for patients with congestive heart failure (CHF) in the context of the general population, especially compared to those with atrial fibrillation (AF).
METHODS Data of patients discharged alive from 2003 to 2012 were extracted from the National Health Insurance Corporation sample cohort. Subjects were classified into control (n=90,277), CHF (n=4533), AF (n=1187), and CHF plus AF (n=1213) groups.
RESULTS CHF was associated with an increased risk for ischemic stroke, which was significant after various adjustment models. Annualized stroke risk was 0.54 (0.52-0.57) per 100 person-years for the control group, 2.00 (1.79-2.21) for the CHF group, 2.27 (1.84-2.69) for the AF group, and 2.87 (2.38-3.36) for the CHF plus AF group. The CHA₂DS₂-VASc scoring schema had a moderate discriminatory value for stroke risk in patients with CHF as well as in AF. The risk of stroke for the CHF group was comparable to that of the AF group when stratified according to the CHA₂DS₂-VASc scores. Those with CHA₂DS₂-VASc score of 0 or 1 were at low risk for stroke for both CHF and AF.
CONCLUSION Patients with CHF are at increased risk for ischemic stroke and thromboembolism. This study showed that the CHA₂DS₂-VASc schema can help stratify stroke risk for individual CHF patients. Stroke is a frequent complication among patients with CHF; therefore, safe and effective strategies to prevent stroke are needed.
PubMed IF 3.3 순환기내과
2492017

제1저자 최의근 · 교신저자 Peng-Sheng Chen

, , ,
Ganglionated plexi as neuromodulation targets for atrial fibrillation.
J Cardiovasc Electrophysiol. 2017;28(12):1485-1491.

Abstract
The autonomic nervous system plays an important role in the genesis of atrial fibrillation and is one of the candidate targets for atrial fibrillation therapy. This review focuses on the role of the autonomic nervous system in atrial fibrillation development and discusses the results of the ganglionated plexi catheter and surgical ablation in preclinical and clinical studies. The heart is innervated by the extrinsic and intrinsic autonomic nervous systems. The intrinsic autonomic nervous system consists of multiple ganglionated plexi and axons, which innervate the neighboring atrial myocardium and control their electrophysiological properties. Abnormal autonomic innervation has been observed in an animal model of atrial fibrillation and in humans. Direct recordings of autonomic nerve activity in canine models showed that atrial tachyarrhythmia episodes were invariably preceded by intrinsic cardiac autonomic nerve activity, thus supporting the importance of intrinsic cardiac autonomic nerve activity as the triggers for atrial tachyarrhythmia. Targeting ganglionated plexi with catheter ablation improves the outcomes of paroxysmal atrial fibrillation ablation in addition to pulmonary vein antrum isolation. Ablation of ganglionated plexi alone without pulmonary vein isolation is also useful in controlling paroxysmal atrial fibrillation in some patients. However, surgical ganglionated plexi ablation in patients with a large left atrium, persistent atrial fibrillation, and/or a history of prior catheter ablation does not result in additional benefits. These different outcomes suggest that ganglionated plexi ablation is effective in managing patients with paroxysmal atrial fibrillation, but its effects in patients with persistent atrial fibrillation and advanced atrial diseases might be limited.
PubMed IF 2.4 순환기내과
2482017

제1저자 유미연 · 교신저자 진호준

, , ,
Short-term anti-proteinuric effect of tacrolimus is not related to preservation of the glomerular filtration rate in IgA nephropathy: A 5-year follow-up study.
PLoS One. 2017;12(11):e0188375.

Abstract
BACKGROUND The immunosuppressive drug tacrolimus has the short-term effect of reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN). Our study investigated the effects on proteinuria and kidney function after discontinuation of tacrolimus.
METHODS Patients with biopsy-proven IgAN were included in the study and randomly divided into two treatment groups. There was a corresponding control group for each treatment group. The first group included patients treated with tacrolimus (Tac vs non-Tac group) and the second group included patients with a renin angiotensin system blocker (RASi vs non-RASi group). The Tac group received treatment for up to 16 weeks, with the administration of tacrolimus being ceased at the final visit (trial phase). We tracked the patients at 12, 24, 52, and 240 weeks (observational phase). The primary outcomes examined were the percentage change (from the trial phase to the observational phase) of time-averaged proteinuria (TA-proteinuria; g/g creatinine [cr]) and the estimated glomerular filtration rate (eGFR). Time-averaged proteinuria was defined as the average of urine protein to creatinine ratio (UPCR), measured every 3 months during both the trial and observational phases of the study.
RESULTS A significant reduction in UPCR was observed in the Tac group compared to non-Tac group at the 4 and 8 week visits during the trial phase (p = 0.023 and p = 0.003, respectively). However, the difference between the Tac group and non-Tac group was not evident in the other review periods, estimated by linear mixed effect model. The percentage change in TA-proteinuria was greater in the Tac group than that in the corresponding control group (116 ± 96% vs. 63 ± 239%, p = 0.004). Therefore, during the observational phase, TA-proteinuria was not significantly different between the Tac group and the non-Tac group (1.150 ± 0.733 g/g cr vs. 1.455 ± 2.017 g/g cr, p = 0.775). The levels of eGFR throughout the observational phase were not significantly different between the two groups. Furthermore, the mean rate of eGFR change throughout both phases of the study was -6.4 ± 5.9 mL/min/1.73 m2/year in the non-Tac group and -5.4 ± 7.9 mL/min/1.73 m2/year in the Tac group (p = 0.988).
CONCLUSION The anti-proteinuric effect of tacrolimus was promptly reversed 3 months after discontinuing the drug. The use of tacrolimus for a short period of time for patients with IgAN temporarily reduces proteinuria, but the data showed no long-term efficacy regarding proteinuria reduction and improvement of renal function.
PubMed IF 2.8 신장내과
2472017

제1저자 김경민 · 교신저자 임수

, , , , , ,
Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report.
Cardiovasc Diabetol. 2017;16(1):146.

Abstract
BACKGROUND The cardiovascular benefits of statins have been proven, but their effect on circulation in small vessels has not been examined fully. We investigated the effect of 20 mg rosuvastatin on biomarkers, including paraoxonase-1 (PON-1) and asymmetric dimethylarginine (ADMA), and on microvascular reactivity.
METHOD We enrolled 20 dyslipidemic patients with type 2 diabetes and 20 age- and body mass index (BMI)-matched healthy controls. Rosuvastatin (20 mg/day) was given to the patient group for 12 weeks. Biochemical parameters, including PON-1 and ADMA, were compared between the patient and control groups, and before and after rosuvastatin treatment in the patient group. Fasting and 2 h postprandial levels of PON-1 and ADMA after mixed-meal challenge were also compared. Microvascular reactivity in a peripheral artery was examined using laser Doppler flowmetry.
RESULTS The respective mean ± standard deviation of age and BMI were 50.1 ± 3.8 year and 25.8 ± 3.7 kg/m² in the patients and 50.2 ± 3.2 year and 25.4 ± 3.4 kg/m² in the controls. The patient group had worse profiles of cardiometabolic biomarkers, including PON-1 and ADMA, than the controls. In the patients treated with 20 mg rosuvastatin, low-density lipoprotein (LDL)-cholesterol decreased from 147.2 ± 26.5 to 68.3 ± 24.5 mg/dL and high-density lipoprotein (HDL)-cholesterol increased from 42.4 ± 5.2 to 44.7 ± 6.2 mg/dL (both P < 0.05). Both fasting and 2 h postprandial levels of PON-1 increased and those of ADMA decreased after treatment with rosuvastatin for 12 weeks. The changes in postprandial levels of both biomarkers were greater than those after fasting. Microcirculation assessed as reactive hyperemia in the patients after an ischemic challenge increased significantly from 335.3 ± 123.4 to 402.7 ± 133.4% after rosuvastatin treatment. The postprandial changes in the biomarkers were significantly associated with improvement of microvascular reactivity.
CONCLUSIONS Rosuvastatin treatment for 12 weeks improved microvascular reactivity with concomitant beneficial changes in the postprandial levels of PON-1 and ADMA. These results suggest that rosuvastatin improves the postprandial cardiometabolic milieu in type 2 diabetes. Trial registration ClinicalTrials.gov: NCT02185963 (July 7, 2014).
PubMed IF 15.6 내분비대사내과
2462017

제1저자 이윤빈, 최종호 · 교신저자 윤정환, 김기진

, , , , , ,
Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation.
Stem Cells Int. 2017;2017:5180579.

Abstract
In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33-a posttranscriptional regulator of CPT1A-in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production-an indicator of mitochondrial function-was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.
PubMed IF 3.6 소화기내과
2452017

제1저자 김현지 · 교신저자 강시혁

, , , , , , , , , ,
Cardiovascular Effects of Long-Term Exposure to Air Pollution: A Population-Based Study With 900 845 Person-Years of Follow-up.
J Am Heart Assoc. 2017;6(11):JAHA.117.007170.

Abstract
BACKGROUND Studies have shown that long-term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter [PM_2.5]) increases the risk of all-cause and cardiovascular mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long-term exposure to air pollution among residents of Seoul, Korea.
METHODS AND RESULTS Healthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person-years). The risk of major cardiovascular events increased with higher mean concentrations of PM_2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29-1.43) per 1 μg/m³ PM_2.5. Other pollutants including PM_2.5-10 of CO, SO₂, and NO₂, but not O₃, were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus.
CONCLUSIONS This large-scale population-based study demonstrated that long-term exposure to air pollution including PM_2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor.
PubMed IF 6 순환기내과
2442017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , ,
Exploring Coronary Circulatory Response to Stenosis and Its Association With Invasive Physiologic Indexes Using Absolute Myocardial Blood Flow and Coronary Pressure.
Circulation. 2017;136(19):1798-1808.

Abstract
BACKGROUND Although invasive physiological assessment for coronary stenosis has become a standard practice to guide treatment strategy, coronary circulatory response and changes in invasive physiological indexes, according to different anatomic and hemodynamic lesion severity, have not been fully demonstrated in patients with coronary artery disease.
METHODS One hundred fifteen patients with left anterior descending artery stenosis who underwent both ¹³N-ammonia positron emission tomography and invasive physiological measurement were analyzed. Myocardial blood flow (MBF) measured with positron emission tomography and invasively measured coronary pressures were used to calculate microvascular resistance and stenosis resistance.
RESULTS With progressive worsening of angiographic stenosis severity, both resting and hyperemic transstenotic pressure gradient and stenosis resistance increased (P<0.001 for all) and hyperemic MBF (P<0.001) and resting microvascular resistance (P=0.012) decreased. Resting MBF (P=0.383) and hyperemic microvascular resistance (P=0.431) were not changed and maintained stable. Both fractional flow reserve and instantaneous wave-free ratio decreased as angiographic stenosis severity, stenosis resistance, and transstenotic pressure gradient increased and hyperemic MBF decreased (all P<0.001). When the presence of myocardial ischemia was defined by both low hyperemic MBF and low coronary flow reserve, the diagnostic accuracy of fractional flow reserve and instantaneous wave-free ratio did not differ, regardless of cutoff values of hyperemic MBF and coronary flow reserve.
CONCLUSIONS This study demonstrated how the coronary circulation changes in response to increasing coronary stenosis severity using ¹³N-ammonium positron emission tomography-derived MBF and invasively measured pressure data. Currently used resting and hyperemic pressure-derived invasive physiological indexes have similar patterns of relationships to the different anatomic and hemodynamic lesion severities.
CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01366404.
PubMed IF 41.3 순환기내과
2432017

제1저자 박연희, 임석아 · 교신저자 정경해

, , , , , , , , , , , , , , , , , , ,
Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer.
Eur J Cancer. 2017;86:385-393.

Abstract
BACKGROUND Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel.
PATIENTS AND METHODS This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate.
RESULTS A total of 118 patients (median age: 50, 24-66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. The mean number of metastatic sites was 3 (range 1-8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (P = 0.457). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2-32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001).
CONCLUSION EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity.
TRIAL REGISTRATION KCSG BR13-11; ClinicalTrials.gov, NCT02263495.
PubMed IF 7.9 혈액종양내과
2422017

제1저자 김형진 · 교신저자 김범석, 박창민

, , , , , , , ,
The prognostic value of CT radiomic features for patients with pulmonary adenocarcinoma treated with EGFR tyrosine kinase inhibitors.
PLoS One. 2017;12(11):e0187500.

Abstract
PURPOSE To determine if the radiomic features on CT can predict progression-free survival (PFS) in epidermal growth factor receptor (EGFR) mutant adenocarcinoma patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) and to identify the incremental value of radiomic features over conventional clinical factors in PFS prediction.
METHODS In this institutional review board-approved retrospective study, pretreatment contrast-enhanced CT and first follow-up CT after initiation of TKIs were analyzed in 48 patients (M:F = 23:25; median age: 61 years). Radiomic features at baseline, at 1st first follow-up, and the percentage change between the two were determined. A Cox regression model was used to predict PFS with nonredundant radiomic features and clinical factors, respectively. The incremental value of radiomic features over the clinical factors in PFS prediction was also assessed by way of a concordance index.
RESULTS Roundness (HR: 3.91; 95% CI: 1.72, 8.90; P = 0.001) and grey-level nonuniformity (HR: 3.60; 95% CI: 1.80, 7.18; P<0.001) were independent predictors of PFS. For clinical factors, patient age (HR: 2.11; 95% CI: 1.01, 4.39; P = 0.046), baseline tumor diameter (HR: 1.03; 95% CI: 1.01, 1.05; P = 0.002), and treatment response (HR: 0.46; 95% CI: 0.24, 0.87; P = 0.017) were independent predictors. The addition of radiomic features to clinical factors significantly improved predictive performance (concordance index; combined model = 0.77, clinical-only model = 0.69, P<0.001).
CONCLUSIONS Radiomic features enable PFS estimation in EGFR mutant adenocarcinoma patients treated with first-line EGFR TKIs. Radiomic features combined with clinical factors provide significant improvement in prognostic performance compared with using only clinical factors.
PubMed IF 2.8 혈액종양내과
2412017

제1저자 홍준식 · 교신저자 김석진

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Improved prognostic stratification using NCCN- and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma.
Oncotarget. 2017;8(54):92171-92182.

Abstract
The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.
PubMed IF 5.168 혈액종양내과
2402017

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , ,
Clinical Relevance of 18F-Sodium Fluoride Positron-Emission Tomography in Noninvasive Identification of High-Risk Plaque in Patients With Coronary Artery Disease.
Circ Cardiovasc Imaging. 2017;10(11):CIRCIMAGING.117.006704.

Abstract
BACKGROUND ¹⁸F-sodium fluoride (¹⁸F-NaF) positron-emission tomography has been introduced as a potential noninvasive imaging tool to identify plaques with high-risk characteristics in patients with coronary artery disease. We sought to evaluate the clinical relevance of ¹⁸F-NaF uptake using optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography in patients with coronary artery disease.
METHODS AND RESULTS The target population consisted of 51 prospectively enrolled patients (93 stenoses) who underwent ¹⁸F-NaF positron-emission tomography before invasive coronary angiography. ¹⁸F-NaF uptake was compared with IVUS- and OCT-derived plaque characteristics. In the coronary computed tomography angiography subgroup (46 lesions), qualitative lesion characteristics were compared between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative plaques using adverse plaque characteristics. The plaques with ¹⁸F-NaF uptake showed significantly higher plaque burden, more frequent posterior attenuation and positive remodeling in IVUS, and significantly higher maximum lipid arc and more frequent microvessels in OCT (all P<0.05). There were no differences in minimum lumen area and area of calcium between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative lesions. Among 51 lesions with ¹⁸F-NaF-positive uptake, 48 lesions (94.1%) had at least one of high-risk characteristics. The ¹⁸F-NaF tissue-to-background ratio in plaques with high-risk characteristics was significantly higher than in those without (1.09 [95% confidence interval, 0.85-1.34] versus 0.62 [95% confidence interval, 0.42-0.82], P<0.001 for IVUS definition; 0.76 [95% confidence interval, 0.54-0.98] versus 0.42 [95% confidence interval, 0.21-0.62], P=0.014 for OCT definition). Among the 15 lesions that met both IVUS- and OCT-defined criteria for high-risk plaque, 14 (93.3%) showed ¹⁸F-NaF-positive uptake. There was no difference in the prevalence of plaques with any adverse plaque characteristics between ¹⁸F-NaF-positive and ¹⁸F-NaF-negative plaques in the coronary computed tomography angiography subgroup (85.2% versus 78.9%; P=0.583).
CONCLUSIONS This study's results suggest that ¹⁸F-NaF positron-emission tomography can be a useful noninvasive diagnostic tool to identify and localize plaque with high-risk characteristics.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02388412.
PubMed IF 9.1 순환기내과

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