SCI 발표논문

전체 4,588편

22182017

제1저자 정소현 · 교신저자 오국환, 김인화

, , ,
Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients.
PLoS One. 2017;12(2):e0170535.

Abstract
Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development.
PubMed IF 2.8 신장내과
22172017

제1저자 이성우 · 교신저자 진호준

, , , , , ,
Tubular B7-1 expression parallels proteinuria levels, but not clinical outcomes in adult minimal change disease patients.
Sci Rep. 2017;7:41859.

Abstract
B7-1 is thought to play a pathogenic role in minimal-change disease (MCD). Recently, however, doubts have arisen regarding the role of B7-1 expression in MCD. Therefore, we aimed to identify the presence and clinical significance of B7-1 expression in MCD patients. The study participants included 28 adult MCD patients for whom kidney specimens were available. The intensity of B7-1 expression was assessed by two independent specialists. We analysed the association between the intensity of B7-1 expression and clinicopathological variables. No B7-1 expression in the glomeruli was observed in any of the 28 patients. Unexpectedly, however, 75.0% of the patients exhibited tubular B7-1 expression, with 35.7% demonstrating weak positive expressions and 39.3% demonstrating strong positive expressions. The level of proteinuria significantly increased as the intensity of tubular B7-1 expression increased. We also found trends of increasing blood urea nitrogen and serum creatinine levels with increased intensity of tubular B7-1 expression. However, we could not observe definite differences in long- and short-term clinical outcomes depending on the intensity of tubular B7-1 expression. In conclusion, B7-1 was expressed in renal tubular cells but not in glomeruli in adult MCD patients. The intensity of tubular B7-1 expression paralleled proteinuria levels, but not clinical outcomes.
PubMed IF 4.9 신장내과
22162017

제1저자 박지명 · 교신저자 임재준

, , , ,
Progression and Treatment Outcomes of Lung Disease Caused by Mycobacterium abscessus and Mycobacterium massiliense.
Clin Infect Dis. 2017;64(3):301-308.

Abstract
BACKGROUND Mycobacterium abscessus and Mycobacterium massiliense are grouped as the Mycobacterium abscessus complex. The aim of this study was to elucidate the differences between M. abscessus and M. massiliense lung diseases in terms of progression rate, treatment outcome, and the predictors thereof.
METHODS Between 1 January 2006 and 30 June 2015, 56 patients and 54 patients were diagnosed with M. abscessus and M. massiliense lung diseases, respectively. The time to progression requiring treatment and treatment outcomes were compared between the 2 groups of patients, and predictors of progression and sustained culture conversion with treatment were analyzed. In addition, mediation analysis was performed to evaluate the effect of susceptibility to clarithromycin on treatment outcomes.
RESULTS During follow-up, 21 of 56 patients with M. abscessus lung diseases and 21 of 54 patients with M. massiliense lung diseases progressed, requiring treatment. No difference was detected in the time to progression between the 2 patient groups. Lower body mass index, bilateral lung involvement, and fibrocavitary-type disease were identified as predictors of disease progression. Among the patients who began treatment, infection with M. massiliense rather than M. abscessus and the use of azithromycin rather than clarithromycin were associated with sustained culture conversion. The difference in treatment outcomes was partly mediated by the organism's susceptibility to clarithromycin.
CONCLUSIONS Progression rates were similar but treatment outcomes differed significantly between patients with lung disease caused by M. abscessus and M. massiliense. This difference in treatment outcomes was partly explained by the susceptibility of these organisms to clarithromycin.
PubMed IF 8.3 호흡기내과
22152017

제1저자 임수 · 교신저자 박경수

, , , , , , , , ,
Attenuation of carotid neointimal formation after direct delivery of a recombinant adenovirus expressing glucagon-like peptide-1 in diabetic rats.
Cardiovasc Res. 2017;113(2):183-194.

Abstract
AIMS Enhancement of glucagon-like peptide-1 (GLP-1) reduces glucose levels and preserves pancreatic β-cell function, but its effect against restenosis is unknown.
METHODS AND RESULTS We investigated the effect of subcutaneous injection of exenatide or local delivery of a recombinant adenovirus expressing GLP-1 (rAd-GLP-1) into carotid artery, in reducing the occurrence of restenosis following balloon injury. As a control, we inserted β-galactosidase cDNA in the same vector (rAd-βGAL). Otsuka Long-Evans Tokushima rats were assigned to three groups (n = 12 each): (1) normal saline plus rAd-βGAL delivery (NS + rAd-βGAL), (2) exenatide plus rAd-βGAL delivery (Exenatide + rAd-βGAL), and (3) normal saline plus rAd-GLP-1 delivery (NS + rAd-GLP-1). Normal saline or exenatide were administered subcutaneously from 1 week before to 2 weeks after carotid injury. After 3 weeks, the NS + rAd-βGAL group showed the highest intima-media ratio (IMR; 3.73 ± 0.90), the exenatide + rAd-βGAL treatment was the next highest (2.80 ± 0.51), and NS + rAd-GLP-1 treatment showed the lowest IMR (1.58 ± 0.48, P < 0.05 vs. others). The proliferation and migration of vascular smooth muscle cells and monocyte adhesion were decreased significantly after rAd-GLP-1 treatment, showing the same overall patterns as the IMR. In injured vessels, the apoptosis was greater and MMP2 expression was less in the NS + rAd-GLP-1 than in the exenatide or rAd-βGAL groups. In vitro expressions of matrix metalloproteinases-2 and monocyte chemoattractant protein-1 and nuclear factor-kappa-B-p65 translocation were decreased more in the NS + rAd-GLP-1 group than in the other two groups (all P < 0.05).
CONCLUSION Direct GLP-1 overexpression showed better protection against restenosis after balloon injury via suppression of vascular smooth muscle cell migration, increased apoptosis, and decreased inflammatory processes than systemic exenatide treatment. This has potential therapeutic implications for treating macrovascular complications in diabetes.
PubMed IF 12.5 내분비대사내과
22142017

제1저자 이동화 · 교신저자 임수

, , , , , , , , , , ,
Effect of sarpogrelate, a selective 5-HT2A receptor antagonist, on characteristics of coronary artery disease in patients with type 2 diabetes.
Atherosclerosis. 2017;257:47-54.

Abstract
BACKGROUND AND AIMS Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is a potential antiplatelet agent. We performed a randomized study to evaluate the effect of sarpogrelate on vascular health in Korean patients with diabetes.
METHODS Forty diabetic patients aged 58.6 ± 6.8 years with 10-75% coronary artery stenosis, as assessed by coronary computed tomography angiography, were randomly assigned to sarpogrelate 300 mg/day plus aspirin 100 mg/day (SPG + ASA group) or aspirin 100 mg/day alone (ASA group) for 6 months. The primary endpoint of this study was the change in coronary artery disease including the calcium score (CACS), maximal stenosis, and plaque volume (calcified vs. noncalcified). The secondary endpoints were changes in biochemical parameters related to glucose and lipid metabolism, and in subclinical atherosclerosis assessed by ankle-brachial index and pulse wave velocity.
RESULTS After 6-month treatment, there was no significant difference in the changes in CACS, coronary stenosis, ankle-brachial index, and pulse wave velocity, between groups. The total plaque volume decreased from 82.4 ± 14.5 mm³ to 74.6 ± 14.4 mm³ in the SPG + ASA group, but increased from 64.9 ± 16.0 mm³ to 68.6 ± 16.3 mm³ in the ASA group (p < 0.05), mainly driven by changes in the noncalcified component (SPG + ASA group 15.6 ± 4.6 mm³ to 11.2 ± 3.7 mm³vs. ASA group 21.2 ± 6.2 mm³ to 22.8 ± 6.6 mm³, p < 0.01). Serum C-reactive protein levels and homeostasis model assessment of insulin resistance tended to decrease in the SPG + ASA group, but they were not altered in the ASA group.
CONCLUSIONS The present study demonstrated that sarpogrelate treatment may decrease coronary artery plaque volume, particularly the noncalcified portion, in patients with diabetes.
PubMed IF 7.1 내분비대사내과
22132017

제1저자 박지인 · 교신저자 이정표

, , , , , , , , , ,
Comparison of outcomes between the incremental and thrice-weekly initiation of hemodialysis: a propensity-matched study of a prospective cohort in Korea.
Nephrol Dial Transplant. 2017;32(2):355-363.

Abstract
BACKGROUND Recent reports have suggested the possible benefit of beginning hemodialysis (HD) at a rate less frequent than three times weekly and incrementally increasing the dialysis dose. However, the data regarding the benefits and safety of incremental HD are insufficient.
METHODS We analyzed 927 patients with newly initiated HD from the Clinical Research Center for End-Stage Renal Disease cohort from 2008 to 2014. The patients were classified into a thrice-weekly initiation group or an incremental initiation group (one to two sessions per week) according to the frequency of HD per week at baseline. We compared health-related quality of life (HRQOL), daily urine volume at 12 months and all-cause mortality between the groups. We matched the thrice-weekly and incremental groups at a 1:2 ratio using propensity score matching.
RESULTS A total of 312 patients (207 in the thrice-weekly group and 105 in the incremental group) were selected. All-cause mortality was comparable between the two groups before and after propensity score matching. The HRQOL tended to be better in the incremental group for the majority of domains of the Kidney Disease Quality of Life Short Form and Beck's Depression Inventory; however, only the symptoms and problems domain was significantly better in the incremental group at 3 months after HD. At 12 months after HD, there were no differences between the groups. The daily urine volume at 12 months after HD was similar between the two groups.
CONCLUSIONS Incremental HD initiation showed comparable results to thrice-weekly initiation for HRQOL, residual renal function and all-cause mortality. Incremental HD may be considered an additional option for HD initiation in selected patients.
PubMed IF 8.3 신장내과
22122017

제1저자 강은정 · 교신저자 오국환

, , , , , , , , , , ,
Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).
J Korean Med Sci. 2017;32(2):221-230.

Abstract
The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m². The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.
PubMed IF 3.2 신장내과
22112017

제1저자 송경호, 정숙인 · 교신저자 이신원

, , , , , , , , , , , , , , , ,
Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort.
Eur J Clin Microbiol Infect Dis. 2017;36(2):285-294.

Abstract
Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 10⁷ CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.
PubMed IF 3.2 감염내과
22102017

제1저자 송영신 · 교신저자 임수

, , , , , , ,
Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012.
Diabetes Metab J. 2017;41(1):38-50.

Abstract
BACKGROUND The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.
METHODS Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.
RESULTS The percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.
CONCLUSION Application of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.
PubMed IF 8.2 내분비대사내과
22092017

제1저자 나선희 · 교신저자 김남중

, , , , , , , , , , ,
Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites.
Scand J Gastroenterol. 2017;52(2):199-203.

Abstract
OBJECTIVE Ascitic fluid infections (AFI) in cirrhotic patients can be classified into two groups: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). The aim of this study was to compare the clinical characteristics and outcomes of the two groups of patients with AFI.
METHODS We retrospectively reviewed the medical records of cirrhotic patients with AFI. We evaluated demographic data, clinical presentations of AFI, laboratory findings, liver function, and mortality rates.
RESULTS Between January 2005 and December 2014, 533 patients with AFI were evaluated; 259 (48.6%) had SBP and 274 (51.4%) CNNA. Ascites neutrophil count (4410/mm³ versus 1046/mm³, p < .001) and the blood culture positive rate (38.1% versus 20.1%, p < .001) were higher in the SBP group, which also had a higher MELD score (24.29 versus 22.05, p = .004). Seven-day mortality was higher in the SBP group (9.4% versus 4.5%, p = .027) but there was no significant difference in 30-day (22.1% versus 17.5%) or 90-day mortality rate (36.1% versus 36.4%).
CONCLUSIONS Patients in the SBP group had a higher MELD score, ascites neutrophil count, and positive blood culture rate. Although seven-day mortality rate was higher in the SBP group, the 30-day and 90-day mortality rates were similar in the two groups.
PubMed IF 1.8 감염내과
22082017

제1저자 한지혜, 오태정 · 교신저자 임수

, , , , , , , , , , ,
The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE -/- mice fed a western diet.
Diabetologia. 2017;60(2):364-376.

Abstract
AIMS/HYPOTHESIS A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action.
METHODS Forty-eight 5-week-old male ApoE ^-/- mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic arch/valve areas and cardiovascular risk variables in the blood and tissues were evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body composition was determined using dual-energy x-ray absorptiometry.
RESULTS After 8 weeks of treatment, the empagliflozin and glimepiride groups exhibited decreased blood glucose levels. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the empagliflozin groups than in the control or glimepiride groups. Insulin resistance and circulating concentrations of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and urinary microalbumin decreased after empagliflozin treatment, and this significantly correlated with plaque size. Empagliflozin treatment reduced weight and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in plaque and adipose tissue compared with the control or glimepiride group. Empagliflozin treatment increased adiponectin levels.
CONCLUSIONS/INTERPRETATION Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by empagliflozin.
PubMed IF 10.4 내분비대사내과
22072017

제1저자 김광일 · 교신저자 Steven Steinhubl

, ,
Digital technology to enable aging in place.
Exp Gerontol. 2017;88:25-31.

Abstract
Aging, both of individuals and populations, presents challenges and opportunities. The multitude of morbidities and disabilities that are a too common component of aging represent significant challenges to individuals, their families and to healthcare systems. Aging in place is the ability to safely and comfortably maintain an independent and high quality of life in one's own home and community and is a highly desirable goal of most individuals with the additional benefit of significantly impacting the impending enormous healthcare burden. In order to make this possible, new care models that take advantage of novel technologies for tracking important physiologic and safety parameters need to be developed and implemented. By thoughtfully doing so, it can be possible to seamlessly provide preventative interventions when and as needed, detect the earliest signs of aggravation of chronic conditions, or identify and respond to any emergency situations, such as falls or cardiac arrest. In contrast to current approaches, caring for elderly individuals in their homes based on a digital technology infrastructure could be effective and cost-saving. In this review, we provide an overview of the characteristics of potential digital solutions applicable to creative aging along with the existing evidence supporting their ability to improve care, increase quality of life, and substantially decrease the emotional and financial costs associated with aging.
PubMed IF 5.1 순환기내과
22062017

제1저자 황재진 · 교신저자 이동호

, , , , ,
Clinicopathological characteristics of patients who underwent additional gastrectomy after incomplete endoscopic resection for early gastric cancer.
Medicine (Baltimore). 2017;96(7):e6172.

Abstract
To evaluate the clinicopathological characteristics and factors that lead to residual tumors in patients who underwent additional gastrectomy for incomplete endoscopic resection (ER) for early gastric cancer (EGC).Between 2003 and 2013, the medical records of patients underwent additional gastrectomy after incomplete ER were retrospectively reviewed. Those diagnosed with the presence of histologic residual tumor in specimens obtained by gastrectomy were assigned to the residual tumor (RT) group (n = 47); those diagnosed with the absence of histologic residual tumor were assigned to the nonresidual tumor (NRT) group (n = 33).In the multivariate analysis, endoscopic piecemeal resection, Helicobacter pylori infection, large tumor size (>2 cm), and both (lateral and vertical) marginal involvement were independent factors of the presence of residual tumor in additional gastrectomy after incomplete resection ER for EGC and the rates of independent factors were significantly higher in the RT group than in the NRT group (P < 0.05).Before ER, preexamination to accurately determine the GC invasion depth and the presence of LN metastasis is very important. During ER, surgeons should attempt to perform en bloc resection and to resect the mucous membrane with adequate safety margins to prevent tumor invasion into the lateral and vertical margins.
PubMed IF 2 소화기내과
22052017

제1저자 양민석 · 교신저자 강혜련

, , , , , ,
True rise in anaphylaxis incidence: Epidemiologic study based on a national health insurance database.
Medicine (Baltimore). 2017;96(5):e5750.

Abstract
The incidence trend of anaphylaxis in Asia is not well investigated. The aim of this study is to estimate the entire population-based incidence of anaphylaxis in Korea using a nationwide administrative database.Data over a 7-year period (2008-2014) was obtained from the Korean National Health Insurance (NHI) claims database which covers 97.9% of the entire Korean population. Using diagnosis codes from the International Classification of Diseases-10 for anaphylaxis (T78.0, T78.2, T80.5, and T88.6), we identified the annual number of patients who had visited any hospital with a primary diagnosis of anaphylaxis. Incidence rates were calculated using the population distribution data of all NHI beneficiaries.The incidence of anaphylaxis in Korea was 32.19 episodes per 100,000 person-years in 2014, which nearly doubled from 2008 (16.02 episodes per 100,000 person-years). The incidence of anaphylaxis increased continuously throughout these years regardless of gender and age groups (P for trend < 0.001). Female was significantly less predisposed than male (adjusted odds ratio [OR], 0.69; 95% confident interval [CI], 0.66-0.72; P < 0.001). The incidence was the lowest in 0 to 19 age group and the highest in 40 to 69 age group (adjusted OR, 2.41; 95% CI, 2.29-2.54; P < 0.001).In conclusion, we report the increasing time trend of anaphylaxis incidence rates using nationwide claims database for the first time in Asia.
PubMed IF 2 알레르기내과
22042017

제1저자 김형우 · 교신저자 황진혁

, , , , ,
Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern.
Medicine (Baltimore). 2017;96(5):e5926.

Abstract
Several reports showed that interleukin-6 (IL-6) or -8 (IL-8) might be useful inflammatory biomarkers for pancreatic ductal adenocarcinoma (PDAC), although these clinical impact is still open to debate. The aim of this study was to elucidate whether serum levels of IL-6 and IL-8 at diagnosis could predict the tumor progression pattern of PDAC, especially in extensive hepatic metastasis.According to the tumor burden of hepatic metastasis at the last follow-up, tumor progression pattern was defined as follows: no or limited (unilobar involvement and 5 or less in the within liver, limited group) and extensive hepatic metastasis (bilobar or more than 5, progressed group). Fifty-three PDAC patients with initially no or limited hepatic metastasis were enrolled retrospectively.Around 42 (79.2%) were included in the limited and 11 (20.8%) in the progressed group. The median serum level of IL-6 in the progressed group was elevated significantly compared with the limited group. However, the median serum level of IL-8 was not. Furthermore, multivariate analysis revealed that the elevated serum level of IL-6 was an independent risk factor for progression to extensive hepatic metastasis (odds ratio 1.928, 95% confidence interval 1.131-3.365, P = 0.019), but IL-8 was not. However, higher IL-6 did not predict shorter survival.High serum IL-6 can be an independent risk factor for progression to extensive hepatic metastasis in PDAC patients.
PubMed IF 2 소화기내과
22032017

제1저자 이동현 · 교신저자 이정훈, 정용진

, , , , , , , , , , , , , ,
Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area.
PLoS One. 2017;12(1):e0170394.

Abstract
BACKGROUND Recently, a modified insulin-like growth factor-1 (IGF)-Child-Turcotte-Pugh (CTP) classification was proposed to improve the original CTP classification. This study aimed to validate the new IGF-CTP classification system as a prognostic maker for patients with hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area.
METHODS We conducted a post-hoc analysis of a prospective cohort study. We used Harrell's C-index and U-statistics to compare the prognostic performance of both IGF-CTP and CTP classifications for overall survival. We evaluated the relationship between HCC stage and the four components of the IGF-CTP classification (serum levels of IGF-1, albumin, and total bilirubin and prothrombin time [PT]) using nonparametric trend analysis.
RESULTS We included a total of 393 patients in this study. In all, 55 patients died during the median follow-up of 59.1 months. There was a difference between IGF-CTP class and CTP class in 14% of patients. Overall, the IGF-CTP classification system had a higher prognostic value (C-index = 0.604, 95% confidence interval [CI] = 0.539-0.668) than the CTP system (C-index = 0.558, 95% CI = 0.501-0.614), but the difference was not statistically significant (P = .07 by U-statistics). A lower serum level of IGF-1 was related to a more advanced cancer stage (P < .01). The remaining components of the IGF-CTP classification were not significantly related to tumor stage (P = .11 for total bilirubin; P = .33 for albumin; and P = .39 for PT).
CONCLUSIONS The IGF-CTP classification was slightly better than the original CTP classification for predicting survival of patients with HCC in a chronic hepatitis B endemic area. This is most likely due to the fact that serum IGF-1 levels reflect underlying HCC status.
PubMed IF 2.8 소화기내과
22022017

제1저자 강시혁 · 교신저자 연태진

, , , , , , , , , , ,
Angiographic outcomes of Orsiro biodegradable polymer sirolimus-eluting stents and Resolute Integrity durable polymer zotarolimus-eluting stents: results of the ORIENT trial.
EuroIntervention. 2017;12(13):1623-1631.

Abstract
AIMS We performed a randomised controlled open-label non-inferiority trial to compare angiographic outcomes between the ultra-thin strut, biodegradable hybrid polymer Orsiro sirolimus-eluting stent (O-SES) and the durable biocompatible polymer Resolute Integrity zotarolimus-eluting stent (R-ZES).
METHODS AND RESULTS A total of 372 patients planned to undergo percutaneous coronary revascularisation were randomly assigned 2:1 to treatment with O-SES or R-ZES (250 and 122 patients, respectively). O-SES was non-inferior to R-ZES for the primary endpoint, in-stent late lumen loss at nine months (median 0.06 mm [interquartile range, -0.09 to 0.24 mm] versus 0.12 mm [-0.07 to 0.32 mm]; p for non-inferiority <0.001; p for superiority=0.205). Percent diameter stenosis was significantly lower in the O-SES group than in the R-ZES group (15.0 [10.0 to 20.0] versus 20.0 [13.3 to 26.0]; p=0.002). Target lesion failure occurred in 2.4% and 3.3% of the O-SES and R-ZES groups, respectively (p=0.621). Subgroup analyses showed consistently similar outcomes between the two groups in terms of the primary endpoint, except for the diabetic subgroup.
CONCLUSIONS O-SES was non-inferior to R-ZES in terms of in-stent late loss at nine months. Angiographic restenosis and clinical adverse events were low in both groups. This study confirms the good safety and efficacy profiles of both contemporary coronary stents.
PubMed IF 9.2 순환기내과
22012017

제1저자 김경아 · 교신저자 정숙향

, , ,
Nationwide Seropositivity of Hepatitis A in Republic of Korea from 2005 to 2014, before and after the Outbreak Peak in 2009.
PLoS One. 2017;12(1):e0170432.

Abstract
BACKGROUND/AIMS The epidemiologic shift of hepatitis A virus (HAV) infection in the South Korean population resulted in a peak outbreak of hepatitis in 2009. The aim of this study was to clarify the seropositivity of anti-HAV antibody (anti-HAV) and its demographic characteristics before and after the peak outbreak from 2005 to 2014.
METHODS This retrospective study analyzed the anti-HAV data of all individuals from 1,795 medical institutions referred to a major central laboratory from January 2005 through December 2014, as a sentineal tool for monitoring annual variation of anti-HAV positivity. The prevalence of anti-HAV was adjusted for age and area with the standard population based on the 2010 Census data.
RESULTS A total of 424,245 individuals were included in this study. The overall age-adjusted anti-HAV prevalence decreased from 65.6% in 2005 to 62.2% in 2014. During the 10-year period, the seroprevalence continuously decreased in persons aged 30 to 39 years (69.6% to 32.4%) and those aged 40 to 49 years (97.9% to 79.3%) due to the cohort effect. In contrast, it increased in persons aged 10 to 19 years (15.4% to 35.2%), while it was the lowest (8.7%) in 2010 before rebounding to 20.2% in 2014 in persons aged 20 to 29 years due to a vaccination effect.
CONCLUSION Although the HAV vaccination rate increased, the anti-HAV seropositivity in South Korea decreased from 65.6% to 62.2% in this study population. In particular, the immunity of young adults was still low, and an outbreak of HAV is possible in the near future. Therefore, continuous monitoring and optimal preventive measures to prevent future outbreaks should be considered.
PubMed IF 2.8 소화기내과
22002017

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
21992017

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
21982017

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
21972017

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
21962017

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
21952017

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
21942017

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
21932017

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
21922017

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
21912017

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
21902017

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
21892017

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

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