SCI 발표논문

2017년 269편

292017

제1저자 남준열 · 교신저자 이정훈, 김휘영

, , , , , , , , , , , , , ,
Oral Medications Enhance Adherence to Surveillance for Hepatocellular Carcinoma and Survival in Chronic Hepatitis B Patients.
PLoS One. 2017;12(1):e0166188.

Abstract
BACKGROUND/AIMS Regular surveillance for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients is essential to detect HCC earlier and to improve prognosis. This study investigated whether prescription of oral medication contributes to adherence to surveillance, early tumor detection, and overall survival (OS).
METHODS A total of 401 CHB patients who were newly diagnosed with HCC were included: 134 patients received no medication (group 1), 151 received hepatoprotective agents such as ursodeoxycholic acid and silymarin (group 2), and 116 received antiviral agents (group 3) at two years before HCC diagnosis. The primary endpoint was OS, and secondary endpoints were compliance to regular surveillance and HCC status at diagnosis.
RESULTS Compared to group 1, both group 2 and 3 had higher rates of good compliance to regular surveillance (defined as participation in >80% of imaging intervals being ≤6 months) (58.2%, 90.1%, and 97.4%, respectively; P<0.001), more HCC diagnosed at a very early stage (20.9%, 32.5%, and 36.2%; P = 0.019) and smaller tumor size (2.8±2.4cm, 1.9±1.1cm, and 1.8±0.9cm; P<0.001). Finally, compared to group 1, both group 2 (hazard ratio, 0.63; 95% confidence interval, 0.41-0.97; P = 0.035) and group 3 (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P = 0.002) had significantly longer OS. In mediation analysis, prolonged OS is resulted considerably from indirect effect mediated by shorter imaging interval (>100% in group 2 and 14.5% in group 3) rather than direct effect of medication itself.
CONCLUSIONS Prescription of oral medication improves compliance to surveillance and enables early detection of HCC, which is associated with enhanced survival.
PubMed IF 2.8 소화기내과
282017

제1저자 전예주 · 교신저자 정숙향

, , , ,
Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions.
Gut Liver. 2017;11(1):136-141.

Abstract
BACKGROUND/AIMS α-Fetoprotein (AFP) is normally <10 ng/mL in adults without malignancy or liver regeneration. However, hereditary or nonhereditary persistence of AFP in healthy adults may be encountered in clinical practice. This study describes four cases of persistent AFP elevation in healthy adults and investigates mutations in key transcription regulatory regions of the AFP gene as potential drivers of AFP overexpression.
METHODS Four healthy adults with persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20 controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP levels were collected from the families of two of the patients. We sequenced five regions that are critical for AFP expression: a promoter, two enhancers, and two silencers.
RESULTS One of the two cases in which family information was represented is the first case of hereditary persistence of AFP in South Korea. Mutations related to AFP overexpression were not found in the transcription regulatory regions among the four patients.
CONCLUSIONS Persistent AFP elevation is a heterogeneous condition with or without a hereditary pattern and may be caused by factors outside of transcription regulatory region changes. Further research on the mechanism of AFP elevation is needed.
PubMed IF 4.1 소화기내과
272017

제1저자 윤혁 · 교신저자 김상균

, , , , , , ,
Helicobacter pylori Eradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis.
Gut Liver. 2017;11(1):79-86.

Abstract
BACKGROUND/AIMS To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter pylori (HP) infection and after HP eradication.
METHODS We divided non-cancer patients into four groups according to the status of HP infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We compared cIAP2 mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression of cIAP2 messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferasemediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy.
RESULTS The expression of cIAP2 mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/ IM(-) groups (p<0.005). In the HP eradication group, the expression of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period.
CONCLUSIONS The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.
PubMed IF 4.1 소화기내과
262017

제1저자 김상균, 지선미 · 교신저자 김재준

, , , , , , , , , , , , , , , , ,
Quality of Life after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Prospective Multicenter Cohort Study.
Gut Liver. 2017;11(1):87-92.

Abstract
BACKGROUND/AIMS Endoscopic submucosal dissection (ESD) has been an established treatment for indicated early gastric cancer (EGC) without deterioration of quality of life (QOL) compared with surgical resection. The aim of this study was to evaluate long-term QOL in patients undergoing ESD for EGC.
METHODS Patients scheduled to undergo curative ESD for EGC were prospectively enrolled from 12 institutions between May 2010 and December 2011. Assessments of QOL with Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and a gastric cancer-specific questionnaire (STO22) were performed at baseline and at 7 days, 3 months, and 6 months after ESD.
RESULTS A total of 666 subjects were assessed for QLQ-C30 and QLQ-STO22. The mean QLQ-C30 score was 69.5 at baseline, 68.8 at 7 days, 73.1 at 3 months, and 73.2 at 6 months. The global health status on the EORTC QLQ-C30 was significantly improved after 3 and 6 months (p=0.0003 and p<0.0001, respectively). The QLQ-C30 and STO22 scores were not significantly different, or they only slightly deteriorated between before and immediately after ESD, but they were significantly improved after 3 and 6 months (p<0.05).
CONCLUSIONS QOL did not deteriorate immediately after ESD, and it improved more significantly at up to 6 months in patients who underwent curative ESD for EGC without significant complications.
PubMed IF 4.1 소화기내과
252017

제1저자 한승석 · 교신저자 나기영

, , , , , , , ,
Usefulness of Preoperative Echocardiography to Predict Acute Kidney Injury and Long-Term Mortality After Coronary Artery Bypass Grafting.
Am J Cardiol. 2017;119(2):231-236.

Abstract
Acute kidney injury (AKI) is a common complication in patients undergoing coronary artery bypass grafting (CABG), which is associated with significant morbidity and mortality. This study identified echocardiographic predictors of AKI and determined whether these predictors were related to long-term mortality in CABG. This retrospective cohort study included 1,300 patients who underwent echocardiography before CABG at 2 tertiary referral centers from 2004 to 2010. The best echocardiographic predictor of AKI was determined using multivariate and stepwise selection methods. Patients were followed for 72 ± 28.8 months (maximum 11 years) for all-cause mortality. We measured the adjusted odds ratio and hazard ratio for AKI and all-cause mortality, respectively, according to the chosen parameter. E/e' was the best predictor of AKI among echocardiographic parameters. The high E/e' group (>15) exhibited a greater odds ratio for AKI (2.2 [1.51 to 3.27]) than the low E/e' group (<8). The high E/e' group required a longer hospital stay (16 days [12 to 23 days]) than the low E/e' group (14 days [11 to 17 days]). There were 272 deaths (21%) during follow-up. The high E/e' group exhibited a greater hazard ratio for long-term mortality (1.9 [1.34 to 2.76]) than the low E/e' group, and this difference remained statistically significant regardless of the occurrence of AKI and the size of the ejection fraction volume. E/e' in preoperative echocardiography is the best predictor of AKI and long-term mortality in patients undergoing CABG.
PubMed IF 2.5 신장내과
242017

제1저자 조경민 · 교신저자 오도연

, , , , , , , ,
Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer.
Oncotarget. 2017;8(2):2329-2341.

Abstract
BACKGROUND AND PURPOSE Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy.
METHODS We reviewed 450 patients with unresectable BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy.
RESULTS Higher systemic inflammation status also had relation with a primary tumor site (p = 0.003) and higher levels of CEA (p = 0.038). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (6.90 vs. 9.80 months, p =0.002; 7.83 vs. 9.90 months, p =0.041, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) (p < 0.001, p = 0.013 respectively). Results are similar for PLR.
CONCLUSION Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.
PubMed IF 5.008 혈액종양내과
232017

제1저자 김효진 · 교신저자 오국환

, , , , , , , , , ,
Lower Education Level Is a Risk Factor for Peritonitis and Technique Failure but Not a Risk for Overall Mortality in Peritoneal Dialysis under Comprehensive Training System.
PLoS One. 2017;12(1):e0169063.

Abstract
BACKGROUND Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower education level on the development of peritonitis, technique failure, and overall mortality.
METHODS Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (9<academic year≤12, n = 229), and higher than high school (academic year>12, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression.
RESULTS A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20-65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10-2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10-3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53-2.33; P = 0.788) or intent-to-treat analysis (P = 0.726).
CONCLUSIONS Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD.
PubMed IF 2.8 신장내과
222017

제1저자 김수정 · 교신저자 임재준

, , , , , ,
Characteristics associated with progression in patients with of nontuberculous mycobacterial lung disease : a prospective cohort study.
BMC Pulm Med. 2017;17(1):5.

Abstract
BACKGROUND Patients with distinctive morphotype were more susceptible to nontuberculous mycobacterial lung disease (NTM-LD). However, little is known about the association between body morphotype and progression of NTM-LD. The aim of this study was to elucidate predictors of NTM-LD progression, focusing on body morphotype and composition.
METHODS Data from patients with NTM-LD who participated in NTM cohort which started in 1 July 2011 were analyzed. Patients with more than 6 months of follow up were included for analysis. NTM-LD progression was defined as clinician-initiated anti-NTM treatment, based on symptomatic and radiologic aggravation. Body morphotype and composition was measured at entry to the cohort using bioelectrical impedance analysis.
RESULTS NTM-LD progressed in 47 out of 150 patients with more than 6 months of follow up. Patients with middle (adjusted hazard ratio [aHR], 2.758; 95% confidence interval [CI], 1.112-6.843) or lowest tertile (aHR, 3.084; 95% CI, 1.241-7.668) of abdominal fat ratio had a higher risk of disease progression compared with the highest tertile. Other predictors for disease progression were presence of cavity on chest computed tomography (aHR, 4.577; 95% CI, 2.364-8.861), and serum albumin level <3.5 g/dL (aHR, 12.943; 95% CI, 2.588-64.718).
CONCLUSIONS Progression of NTM-LD is associated with body composition. Lower abdominal fat ratio is an independent predictor of NTM-LD progression.
TRIAL REGISTRATION ClinicalTrials.gov, NCT01616745 Registered 25 March 2012.
PubMed IF 3.1 호흡기내과
212017

제1저자 권용환 · 교신저자 김나영

, , , , , , , ,
Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats.
PLoS One. 2017;12(1):e0169113.

Abstract
The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age.
PubMed IF 2.8 소화기내과
202017

제1저자 김지원 · 교신저자 김경임, 윤성수

, , , , , , , , , ,
Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial.
PLoS One. 2017;12(1):e0168854.

Abstract
The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for oral mucositis (OM) induced by intensive chemotherapy with hematopoietic stem cell transplantation. In this phase 2 study, patients were randomized to either rhEGF (50 microg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration of NCI grade ≥2 OM, the incidence of NCI grade ≥3 OM and its duration, and patient-reported quality of life were also similar between the two groups. In the per-protocol analysis, however, the duration of opioid analgesic use was shorter in the rhEGF group (p = 0.036), and recipients in the rhEGF group required a lower cumulative dose of opioid analgesics than those in the placebo group (p = 0.046), among patients with NCI grade ≥2 OM. Adverse events were mild and transient. This study found no evidence to suggest that rhEGF oral spray reduces the incidence of OM. However, further studies are needed to investigate the effect of rhEGF on OM-induced pain reduction after intensive chemotherapy.
PubMed IF 2.8 혈액종양내과
192017

제1저자 이동현, 남준열 · 교신저자 윤정환

, , , , , , , , , ,
Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model.
Cancer Biol Ther. 2017;18(1):67-75.

Abstract
OBJECTIVE Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC.
METHODS Upregulation of natural killer group 2D (NKG2D) ligands (retinoic acid early inducible 1 [RAE-1], mouse; major histocompatibility complex class I polypeptide-related sequence A [MIC-A], human) were evaluated by FACS. VPA concentrations that did not reduce tumor volume were calculated to avoid VPA cytotoxicity in a C3H mouse model of HCC. CIK cells were generated from mouse splenocytes using interferon gamma, a CD3 monoclonal antibody, and interleukin 2. The potential synergistic effect of CIK cells combined with VPA was evaluated in the mouse model and tissue pathology was investigated.
RESULTS After 40 h of incubation with VPA, RAE-1 and MIC-A expression were increased in 4 HCC cell lines compared with that in control (2.3-fold in MH-134, 2.4-fold in Huh-7, 3.7-fold in SNU-761, and 6.5-fold in SNU-475). The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10 mg/kg/day. CIK cells were well generated from C3H mouse splenocytes. After 7 d of treatment with CIK cells plus VPA, a synergistic effect was observed on relative tumor volume in the mouse model of HCC. While the relative tumor volume in untreated control mice increased to 11.25, that in the combination treatment group increased to only 5.20 (P = 0.047).
CONCLUSIONS The VPA-induced increase in NKG2D ligands expression significantly enhanced the effects of CIK cell therapy in a mouse model of HCC.
PubMed IF 5.7 소화기내과
182017

제1저자 안은경, 옥찬영 · 교신저자 오도연

, , , , , , , , , , , , , , , ,
Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment.
Ann Oncol. 2017;28(1):110-115.

Abstract
BACKGROUND A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies.
PATIENTS AND METHODS GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics.
RESULTS Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy.
CONCLUSIONS Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.
PubMed IF 80.4 혈액종양내과
172017

제1저자 하태훈 · 교신저자 고성준

, , , , , , , , , ,
Alcoholic Liver Disease Is Associated with an Increased Risk of Gastric Cancer.
Dig Dis Sci. 2017;62(1):273-279.

Abstract
BACKGROUND Little information is available regarding the relationship between alcoholic liver diseases (ALD) and the development of gastric neoplasia.
AIM The aim of this study was to examine whether ALD is associated with the increased risk of gastric neoplasia.
METHODS We reviewed the medical records 514 patients diagnosed with ALD at Seoul Metropolitan Government Boramae Hospital between January 2000 and December 2011. Control subjects were selected by using propensity score matching (age, sex, and body mass index) from 8190 members of the general population who underwent EGD for screening for gastric neoplasia at Boramae Health Promotion Center during the study period. We compared the frequency of gastric neoplasia between the two groups and evaluated the risk factors for the development of gastric cancer in patients with ALD. In addition, we compared the frequency of gastric cancer between patients with ALD and those with nonalcoholic steatohepatitis (NASH).
RESULTS Of the 514 patients with ALD, 16 patients (3.1 %) had gastric neoplasia, including 14 gastric cancers (2.7 %). The odds of detecting a gastric cancer in ALD patients were approximately 4.77 times greater than in healthy controls [odds ratio (OR) 4.77; 95 % confidence interval (CI) 1.36-16.69; P = 0.007]. ALD (OR 5.32, 95 % CI 1.51-18.68, P = 0.009) was found to be an independent risk factor by multivariate logistic analysis. However, there were no significant differences in the prevalence of gastric adenoma and gastric cancer between patients with ALD and those with NASH.
CONCLUSIONS The rate of gastric cancer was significantly higher in patients with ALD than in healthy controls, suggesting that strict endoscopic surveillance is warranted in patients with ALD.
PubMed IF 2.8 소화기내과
162017

제1저자 김학령 · 교신저자 김명아

, , , , , , , , , , , , , ,
Sex Difference in the Association Between Brachial Pulse Pressure and Coronary Artery Disease: The Korean Women's Chest Pain Registry (KoROSE).
J Clin Hypertens (Greenwich). 2017;19(1):38-44.

Abstract
This study was performed to investigate the association between brachial pulse pressure (PP) and the presence/extent of obstructive coronary artery disease (CAD) in men and women. Study data were obtained from a nation-wide registry composed of 632 patients (173 men and 459 women, 58.1±10.5 years) with suspected CAD who underwent invasive coronary angiography. PP was higher in patients with obstructive CAD (≥50% stenosis) than those without CAD in both sexes (P=.032 in men; P<.001 in women). However, PP increased proportionally with the increasing number of obstructed coronary arteries in women (P<.001) but not in men (P=.070). Multiple logistic-regression analyses demonstrated that higher PP (≥50.5 mm Hg) was an independent factor for determining obstructive CAD even after controlling for potential confounders in women (odds ratio, 2.83; 95% confidence interval, 1.40-5.73; P=.004). These results were consistent in 173 selected women matched with 173 men based on age and CAD severity. In conclusion, the association between brachial PP and obstructive CAD was more pronounced in women than in men. Brachial PP can be a simple and useful indicator of CAD especially in women.
PubMed IF 2.9 순환기내과
152017

제1저자 옥찬영 · 교신저자 오도연

, , , , , , , , ,
Signature of cytokines and angiogenic factors (CAFs) defines a clinically distinct subgroup of gastric cancer.
Gastric Cancer. 2017;20(1):164-174.

Abstract
BACKGROUND Little is known about cytokine and angiogenic factors (CAFs) in gastric cancer (GC) in terms of tumor classification and prognostic value. Here, we aimed to correlate CAF signature with overall survival (OS) in GC.
METHODS We measured pretreatment serum levels of 52 kinds of CAFs in 68 GC patients who were treated with fluoropyrimidine and platinum combination chemotherapy using multiplex bead immunoassays and enzyme-linked immunosorbent assay. We evaluated correlations between CAF levels and pathological features and OS.
RESULTS Three distinct patient groups were identified: one with high levels of proangiogenic factors, another with high levels of proinflammatory factors, and the other with high levels of both factors. Eleven CAFs [interleukin (IL)-2 receptor-alpha, growth-regulated alpha protein, hepatocyte growth factor, macrophage colony-stimulating factor, stromal cell-derived factor, IL-6, IL-8, IL-10, interferon-gamma, vascular endothelial growth factor, and osteopontin] were independently correlated with poor OS. Clustering analysis of these 11 CAFs revealed distinct high and low 11-CAF signature groups. High 11-CAF signature was associated with shorter OS (10.1 vs. 17.9 months, p = 0.026) along with poor performance status, and the presence of signet ring cell components in multivariate analysis of OS (HR 1.76, p = 0.029). The patients' traditional clinicopathological characteristics were not significantly different between the high and low 11-CAF signature groups.
CONCLUSION Serum CAF profiling differentiated GC patient groups. A high 11-CAF signature could identify GC patients with a poor prognosis when treated with standard chemotherapy who need urgent new treatment strategies.
PubMed IF 6.1 혈액종양내과
142017

제1저자 임수 · 교신저자 이문규

, , , , , , , , , , , , , , ,
Efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes: A double-blind randomized controlled trial (INICOM study).
Diabetes Obes Metab. 2017;19(1):87-97.

Abstract
BACKGROUND Gemigliptin is a new dipeptidyl peptidase-IV inhibitor. We investigated the efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes (T2D).
METHODS A total of 433 T2D patients with a glycosylated haemoglobin (HbA1c) level of 7.5% to 11.0% and a fasting plasma glucose (FPG) concentration <270 mg/dL were randomly assigned to 3 groups: (1) gemigliptin 50 mg qd + metformin 1000 to 2000 mg qd (titrated individually), (2) gemigliptin 50 mg qd, or (3) metformin 1000 to 2000 mg qd. The primary end-point was the change in HbA1c level after 24 weeks. Secondary end-points were the changes in FPG, insulin, proinsulin and C-peptide levels. The percentages of responders who achieved an HbA1c level <7% (or <6.5%) were compared between treatment groups.
RESULTS Baseline HbA1c levels were 8.7% in all groups. The mean changes in HbA1c level from baseline to week 24 were -2.06%, -1.24% and -1.47% in the combination, gemigliptin monotherapy and metformin monotherapy groups, respectively. The 95% confidence intervals for between-group differences in HbA1c changes were -1.02 to -0.63 in the combination group vs the gemigliptin group and -0.82 to -0.41 vs the metformin group, which confirmed the superiority of combination therapy. A significantly higher percentage of patients in the combination therapy group reached the target HbA1c level <7% (or <6.5%) compared with the monotherapy groups. No severe side effects were observed.
CONCLUSIONS In T2D patients, the initial combination of gemigliptin and metformin had superior efficacy without safety concerns compared with monotherapy with either drug.
PubMed IF 6.1 내분비대사내과
132017

제1저자 김연욱, 김정희 · 교신저자 박영식

, , , , , ,
Vertebral bone attenuation on low-dose chest CT: quantitative volumetric analysis for bone fragility assessment.
Osteoporos Int. 2017;28(1):329-338.

Abstract
UNLABELLED This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT.
INTRODUCTION Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility.
METHODS A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard.
RESULTS The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05).
CONCLUSION LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.
PubMed IF 5.4 호흡기내과
122017

제1저자 민세희 · 교신저자 한서경, 조영민

, , ,
Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis.
Diabetes Metab Res Rev. 2017;33(1).

Abstract
BACKGROUND Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors.
METHODS We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through June 2015. Randomized controlled trials published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between SGLT2i/INS and DPP4i/INS indirectly with covariates adjustment. Risk of potential bias was assessed.
RESULTS Fourteen eligible randomized controlled trials comprising 6980 patients were included (five SGLT2 inhibitor studies and nine DPP4 inhibitor studies). Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbA_1c [weighted mean difference (WMD) -0.24%, 95% confidence interval (CI) -0.43 to -0.05%], fasting plasma glucose (WMD -18.0 mg/dL, 95% CI -28.5 to -7.6 mg/dL) and body weight (WMD -2.38 kg, 95% CI -3.18 to -1.58 kg) from baseline than DPP4i/INS without increasing the risk of hypoglycaemia (relative risks 1.19, 95% CI 0.78 to 1.82).
CONCLUSIONS Sodium glucose cotransporter 2 inhibitors achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin. There has been no direct comparison of SGLT2 inhibitors and DPP4 inhibitors in patients with T2DM inadequately controlled with insulin therapy. In this study, we performed indirect meta-analysis comparing SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy. Without increasing hypoglycaemia, SGLT2 inhibitors showed better glycaemic control and greater weight reduction than DPP4 inhibitors in patients with T2DM inadequately controlled with insulin. The results of the current study could serve as the best available evidence in selecting oral agents to improve glycaemic control in insulin-treated T2DM patients. Copyright © 2016 John Wiley & Sons, Ltd.
PubMed IF 8.3 내분비대사내과
112017

제1저자 안정남 · 교신저자 이정표

, , , , , , , , , , , ,
Chronic Kidney Disease After Acute Kidney Injury Requiring Continuous Renal Replacement Therapy and Its Impact on Long-Term Outcomes: A Multicenter Retrospective Cohort Study in Korea.
Crit Care Med. 2017;45(1):47-57.

Abstract
OBJECTIVES Severe acute kidney injury requiring continuous renal replacement therapy is associated with a high risk of early mortality. Our objectives were to identify a cohort of early survivors and to follow their renal progress and long-term mortality.
DESIGN Multicenter, observational, retrospective cohort study.
SETTING ICUs in tertiary academic hospitals in Korea.
PATIENTS From 2009 to 2013, we identified 1,764 severe acute kidney injury patients who were started on continuous renal replacement therapy at four hospitals. Of these, we identified 331 survivors for whom we could identify renal function at baseline and at 3 months.
INTERVENTIONS None.
MEASUREMENTS AND MAIN RESULTS The 331 patients were separated into two groups based on their renal function at 3 months after the start of continuous renal replacement therapy. Those who displayed significant deterioration in renal function compared to baseline, defined as greater than or equal to 50% increase in serum creatinine or greater than or equal to 35% decrease in the estimated glomerular filtration rate, or those who continued to receive renal replacement therapy were designated as a "3-month chronic kidney disease progression" group. Those with a return to baseline, less than 50% increase in serum creatinine or less than 35% decrease in the estimated glomerular filtration rate, were designated as a "3-month chronic kidney disease nonprogression" group. The acute kidney injury patients requiring continuous renal replacement therapy showed a higher risk of progression to end-stage renal disease compared to that of stage 3 chronic kidney disease patients who did not undergo an acute kidney injury episode, even if the acute kidney injury was recovered at 3 months after continuous renal replacement therapy initiation. Furthermore, "3-month chronic kidney disease progression" was associated with a high risk of progression to end-stage renal disease and long-term mortality over a median follow-up period of 12.7 (3.8-33.2) and 20.4 (7.5-39.7) months, respectively. Older age, higher baseline serum creatinine levels, and higher blood urea nitrogen concentrations at continuous renal replacement therapy initiation, and lower 24-hour urine output after continuous renal replacement therapy initiation are associated with an increased risk of "3-month chronic kidney disease progression."
CONCLUSIONS Renal functional assessment at 3 months after continuous renal replacement therapy initiation can be useful in predicting progression to end-stage renal disease and long-term mortality. Furthermore, continuous close monitoring and management of acute kidney injury patients requiring continuous renal replacement therapy are required, even in those with recovered renal function.
PubMed IF 7.5 신장내과
102017

제1저자 차용준, 김유정 · 교신저자 이세훈

, , , , , , , , , , , , ,
Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma.
Cancer Res Treat. 2017;49(1):129-140.

Abstract
PURPOSE Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established.
MATERIALS AND METHODS Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups.
RESULTS Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups.
CONCLUSION In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.
PubMed IF 4.2 혈액종양내과
92017

제1저자 정고은 · 교신저자 임정윤

, , , , , , ,
Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease.
Dig Liver Dis. 2017;49(1):57-62.

Abstract
AIMS Hemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD.
METHODS A retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010.
RESULTS Graded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend=0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06-3.10) for women and 1.43 (1.00-2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend=0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73-1.91) in women and 1.76 (1.16-2.66) in men.
CONCLUSIONS The risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.
PubMed IF 4.9 소화기내과
82017

제1저자 차문용,권유욱,안효숙,정효빈 · 교신저자 김효수,묵인희

, , , , , , , , , , , ,
Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease.
Stem Cells Transl Med. 2017;6(1):293-305.

Abstract
Transplantation of stem cells into the brain attenuates functional deficits in the central nervous system via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors. To identify patient-specific and safe stem cells for treating Alzheimer's disease (AD), we generated induced pluripotent stem cells (iPSCs) derived from mouse skin fibroblasts by treating protein extracts of embryonic stem cells. These reprogrammed cells were pluripotent but nontumorigenic. Here, we report that protein-iPSCs differentiated into glial cells and decreased plaque depositions in the 5XFAD transgenic AD mouse model. We also found that transplanted protein-iPSCs mitigated the cognitive dysfunction observed in these mice. Proteomic analysis revealed that oligodendrocyte-related genes were upregulated in brains injected with protein-iPSCs, providing new insights into the potential function of protein-iPSCs. Taken together, our data indicate that protein-iPSCs might be a promising therapeutic approach for AD. Stem Cells Translational Medicine 2017;6:293-305.
PubMed IF 5.9 순환기내과
72017

제1저자 권지현 · 교신저자 윤성수

, , , , , , , , , , , , , , , ,
Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.
Cancer Med. 2017;6(1):100-108.

Abstract
We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD.
PubMed IF 3.5 혈액종양내과
62017

제1저자 구보경 · 교신저자 김원, 김동희

, , , , , , ,
Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis.
J Hepatol. 2017;66(1):123-131.

Abstract
BACKGROUND & AIMS We explored whether sarcopenia is associated with the histological severity of non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) and significant fibrosis.
METHODS In a biopsy-proven NAFLD cohort, the appendicular skeletal muscle mass (ASM) was measured. Sarcopenia was defined as a ASM/body weight (ASM%) value beyond two standard deviations below the mean for healthy young adults.
RESULTS Among the entire set of 309 subjects, the prevalence of sarcopenia in subjects without NAFLD, with non-alcoholic fatty liver (NAFL), and with NASH were 8.7%, 17.9%, and 35.0%, respectively (p<0.001). ASM% was inversely correlated with the severity of fibrosis (p<0.001), and the prevalence of significant fibrosis (⩾F2) was higher in subjects with sarcopenia than in those without (45.7% vs. 24.7%; p<0.001). A crude analysis revealed that sarcopenia was associated with NAFLD (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.58-9.25), which became insignificant after adjustment for body mass index (BMI), diabetes, and hypertension. Among NAFLD subjects, subjects with sarcopenia were more likely to have NASH than those without sarcopenia through a multivariate analysis adjusted for age, gender, BMI, hypertension, diabetes, and smoking status (OR, 2.28; 95% CI, 1.21-4.30), and this finding was obtained even after adjustment for insulin resistance (OR, 2.30; 95% CI, 1.08-4.93). Sarcopenia was also associated with significant fibrosis independent of BMI and insulin resistance (OR, 2.05; 95% CI, 1.01-4.16).
CONCLUSIONS In this large biopsy-proven NAFLD cohort, sarcopenia was significantly associated with NASH and significant fibrosis.
LAY SUMMARY Low muscle mass was found to be associated with histological severity in non-alcoholic fatty liver disease, and sarcopenia was significantly associated with non-alcoholic steatohepatitis and significant fibrosis, independent of obesity, inflammation, and insulin resistance. Clinical trial number: NCT 02206841.
PubMed IF 40.1 소화기내과
52017

제1저자 이승표, 임형준 · 교신저자 정재민, 김용진

, , , , , , , , , , , , ,
Noninvasive Imaging of Myocardial Inflammation in Myocarditis using 68Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography.
Theranostics. 2017;7(2):413-424.

Abstract
The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized ⁶⁸Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with ⁶⁸Ga. The efficacy of ⁶⁸Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. ⁶⁸Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). ⁶⁸Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value<0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value<0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. ⁶⁸Ga-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with ⁶⁸Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis.
PubMed IF 14.9 순환기내과
42017

제1저자 김학령 · 교신저자 조주희

, , , , , ,
Association between arterial stiffness and left ventricular diastolic function in relation to gender and age.
Medicine (Baltimore). 2017;96(1):e5783.

Abstract
Left ventricular (LV) diastolic dysfunction and subsequent overt heart failure are more prevalent in elderly women. Close interaction between arterial stiffness and LV morphology/function has been reported. The aim of this study was to investigate whether there is an age- and gender-dependent relationship between arterial stiffness and LV diastolic function. A total of 819 subjects (58.6 ± 13.3 years, 50.2% men) without structural heart disease (LV ejection fraction ≥50%) were retrospectively analyzed. All participants underwent transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement on the same day. The association of baPWV with septal e' velocity and average E/e' was assessed. In the total study subjects, baPWV was negatively correlated with septal e' velocity (r = 0.383, P < 0.001), and positively correlated with E/e' (r = -0.266, P < 0.001). These linear correlations remained significant even after stratificaion of the study subjects by age (<65 years vs ≥65 years) and genders (P < 0.05 for each). There were obvious differences in baPWV according to groups with normal LV diastolic function, intermediate profile and LV diastolic dysfunction in young (P = 0.010) and elderly (≥65 years) women (P < 0.001) and eldery men (P = 0.012) but not in elderly men (P = 0.270). There was a significant association of baPWV with septal e' velocity (β = -0.258, P = 0.020) and E/e' (β = 0.122, P = 0.030) in elderly women even after controlling for multiple clinical covariates. This independent association was not seen in younger women and men (P > 0.05 for each). In conclusion, baPWV was independently associated with septal e' velocity and E/e' in elderly women but not in younger women or men. The results of this study provide additional evidence that increased arterial stiffness plays an important role in the development of heart failure with preserved ejection fraction as well as LV diastolic dysfunction in elderly women.
PubMed IF 2 순환기내과
32017

제1저자 이진솔 · 교신저자 윤성수

, , , , ,
MCM7 polymorphisms associated with the AML relapse and overall survival.
Ann Hematol. 2017;96(1):93-98.

Abstract
The minichromosome maintenance complex component 7 (MCM7) encodes a member of MCM complex, which plays a critical role in the initiation of gene replication. Due to the importance of MCM complex, MCM7 gene has been regarded as a candidate gene for cancer development. In the present study, seven MCM7 polymorphisms were genotyped in 344 subjects composed of 103 acute myeloid leukemia (AML) patients and 241 normal controls to examine the possible associations between MCM7 polymorphisms and the risk of AML. MCM7 polymorphisms were not associated with the risk of AML (P > 0.05). However, MCM7 polymorphisms were significantly related to the relapse of AML and overall survival. The rs2070215 (N144S) showed a protective effect to the risk of AML relapse (OR = 0.37; P ^corr = 0.02). In haplotype analyses, the ht1 and ht2 showed significant associations with the risk of AML relapse (P ^corr = 0.02-0.03). In addition, rs1534309 showed an association with the overall survival of AML patients. Patients with major homozygote genotype (CC) of rs1534309 showed a higher survival rate than the patients with other genotypes (CG and GG). The results of the present study indicate that MCM7 polymorphisms may be able to predict the prognosis of AML patients.
PubMed IF 2.3 혈액종양내과
22017

제1저자 김선욱 · 교신저자 김광일

, , , , , , ,
Clinical implication of frailty assessment in older patients with atrial fibrillation.
Arch Gerontol Geriatr. 2017;70:1-7.

Abstract
BACKGROUND We aimed to show the frailty status in older AF patients, and to find the association between frailty and the scores of CHA₂DS₂-VASc and HAS-BLED. Ultimately, we sought to investigate the impact of frailty on cardiovascular and all-cause mortality in older AF patients.
METHODS We retrospectively evaluated 365 patients (≥65years old) with AF, who underwent comprehensive geriatric assessment (CGA) between 2007 and 2014 in a single tertiary hospital. The CHA₂DS₂-VASc and HAS-BLED scores were calculated based on the electronic medical records and the frailty index was computed from the CGA data. The primary outcomes were cardiovascular and all-cause mortality.
RESULTS Frailty status was positively associated with the CHA₂DS₂-VASc score (P<0.001) and the HAS-BLED score (P=0.01). Patients with high CHA₂DS₂-VASc and HAS-BLED scores were more likely to be treated with anticoagulants rather than antiplatelet agents. However, frailty status was not associated with antithrombotic therapy. During the follow-up period (median [interquartile range], 22.9 [8.4-42.2] months), 141 patients (38.6%) died, of which 48 were due to cardiovascular events. CHA₂DS₂-VASc score could predict cardiovascular mortality, but not all-cause mortality. In contrast, frailty status was the independent predictor for both cardiovascular and all-cause mortality after adjusting for possible confounders (hazard ratio for all-cause mortality, 4.549; 95% CI, 2.756-7.509; P<0.001).
CONCLUSION Frailty assessment can be used to predict mortality in older AF patients, and provides additional prognostic value, along with the CHA₂DS₂-VASc and HAS-BLED scores.
PubMed IF 4.7 순환기내과
12017

제1저자 송우정 · 교신저자 조상헌

, , , , , , , , , , , , , , ,
Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review.
J Allergy Clin Immunol Pract. 2017;5(1):135-143.e1.

Abstract
BACKGROUND Fractional exhaled nitric oxide (Feno) is a safe and convenient test for assessing T_H2 airway inflammation, which is potentially useful in the management of patients with chronic cough.
OBJECTIVE To summarize the current evidence on the diagnostic usefulness of Feno for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough.
METHODS A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of Feno (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2.
RESULTS We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from about 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency.
CONCLUSIONS We did not find strong evidence to support the use of Feno tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence.
PubMed IF 6.6 알레르기내과

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