SCI 발표논문

2012년 229편

492012

제1저자 윤영광 · 교신저자 김태유

, , , , , , ,
Down-regulation of mitogen-inducible gene 6, a negative regulator of EGFR, enhances resistance to MEK inhibition in KRAS mutant cancer cells.
Cancer Lett. 2012;316(1):77-84.

Abstract
Previously, we found that KRAS mutant cancer cells showed variable response to AZD6244, a MEK inhibitor through differential activation of EGFR/AKT. To investigate its mechanism, we performed cDNA microarray using four KRAS mutant cancer cells. We found that treatment with AZD6244 reduced the expression of mitogen-inducible gene 6 (MIG6), a negative feedback regulator for EGFR, in AZD6244-resistant cells, while activity of EGFR and AKT was increased in these cells. Reconstitution or knockdown of MIG6 expression affected cancer cell responses to AZD6244. Treatment with a combination of EGFR inhibitor and AZD6244 inhibited cell proliferation synergistically without activation of AKT in AZD6244-resistant cells. Our study provides a mechanism of differential response to MEK inhibition in KRAS mutant cancer.
PubMed IF 11.8 혈액종양내과
482012

제1저자 이연주 · 교신저자 유철규

, , , , , , , , , ,
The clinical implications of bronchoscopy in hemoptysis patients with no explainable lesions in computed tomography.
Respir Med. 2012;106(3):413-9.

Abstract
INTRODUCTION Hemoptysis is observed frequently in patients, although chest computed tomography (CT) shows no explainable lesion as the cause of hemoptysis. However, the clinical course of these patients has not been reported fully.
METHODS This study included patients who visited Seoul National University Hospital and Seoul National University Bundang Hospital to be treated for hemoptysis from January 2003 through October 2009 and who had no lesion causing hemoptysis in chest CT. We retrospectively analyzed their bronchoscopic and clinical findings.
RESULTS A total of 228 patients were included, and the mean follow-up duration was 781 days. All patients underwent bronchoscopy. The bronchoscopic findings of 191 patients (83.8%) were negative for hemoptysis and showed the possible causes of bleeding in 37 patients (16.2%). Forty-three of the 191 patients with negative bronchoscopic findings had oronasopharyngeal problems or were using anticoagulants. After excluding these 43 patients, hemoptysis recurred in 29 (19.6%) of the remaining patients. Thirteen of the patients whose bronchoscopic findings identified the possible causes of bleeding (35.1%) experienced recurrence. Only one patient (0.4%) was diagnosed with lung cancer by the initial bronchoscopy, and no patient developed malignancy during the follow-up period.
CONCLUSION The recurrence rate was higher in the patients with positive findings than in the patients with negative findings on bronchoscopy. Although about 20% of patients with negative bronchoscopy findings experienced recurrence, the clinical course of those in whom recurrent bleeding occurred was usually benign.
PubMed IF 3.3 호흡기내과
472012

제1저자 이정훈 · 교신저자 윤정환

, , , , , , , , , , ,
Simple scoring system predicting genotypic resistance during rescue therapy for Lamivudine-resistant chronic hepatitis B.
J Clin Gastroenterol. 2012;46(3):243-50.

Abstract
GOAL In this study, we aimed to devise a simple scoring system predicting the risk of genotypic resistance (GR) to current rescue therapies for patients with lamivudine (LAM)-resistant chronic hepatitis B.
BACKGROUND LAM and adefovir (ADV) combination therapy should be recommended for an initial rescue therapy against LAM-resistant hepatitis B virus (HBV). However, there still are many LAM-resistant patients being treated with entecavir (ETV) or ADV monotherapy.
STUDY This retrospective cohort study included consecutive patients treated for LAM-resistant chronic hepatitis B with ETV or ADV monotherapy, or LAM/ADV combination therapy. The cumulative probabilities of GR and virological responses and breakthrough according to clinical variables were analyzed by survival analyses and derived an index for future GR.
RESULTS A total of 224 patients were included (median treatment duration=117.9 wk). Using risk factors indentified on multivariable analyses, a simple index for future GR (Antiviral Resistance Prediction Index, ARPI) was developed with 3 clinical variables: the rescue therapy regimens (+0, ADV; +1, ETV; +2, LAM/ADV), HBV DNA reduction at 12 weeks (+0, <3 log10 copies/mL; +1, >3 log10 copies/mL), and the initial HBV DNA level (+0, >10 copies/mL; +1, <10 copies/mL). No patient with ARPI ≥2 exhibited GR, whereas 47% of the patients with an ARPI <2 developed GR by week 144 (P=0.005).
CONCLUSIONS The results of this study suggest that the ARPI is a simple and early index that can be used to determine the risk for subsequent GR during rescue therapy for LAM-resistant chronic hepatitis B.
PubMed IF 2.7 소화기내과
462012

제1저자 곽민선 · 교신저자 윤정환

, , , , , , ,
Risk factors, clinical features, and prognosis of the hepatocellular carcinoma with peritoneal metastasis.
Dig Dis Sci. 2012;57(3):813-9.

Abstract
BACKGROUND The clinical features and prognosis of hepatocellular carcinoma (HCC) with peritoneal metastasis have not been fully evaluated.
AIMS This study aimed to investigate the risk factors, clinical features, and prognosis of HCC with peritoneal metastasis.
METHODS Patients who were diagnosed as HCC with peritoneal metastasis and the same number of randomly selected, risk factor-matched HCC controls without peritoneal metastasis were included. The risk factors and overall survival were compared between peritoneal metastasis-positive and -negative groups after adjustment of other variables.
RESULTS HCC rupture was an independent risk factor for peritoneal metastasis in HCC patients (P = 0.008). When the risk factors (age, sex, Child-Pugh score, and intrahepatic tumor stage) were matched, peritoneal metastasis failed to independently affect overall survival (P = 0.511). In the peritoneal metastasis-positive group, advanced Child-Pugh class [hazard ratio (HR), 1.99; 95% confidence interval (CI), 1.07-3.72; P = 0.030] and progressive intrahepatic HCC status (HR, 19.04; 95% CI, 2.55-142.13; P = 0.004) were independent risk factors for early death. Complications such as ileus, bleeding, and hydronephrosis due to rectovesical mass were reported in 1.5-7.4% in the peritoneal metastasis-positive group.
CONCLUSIONS Peritoneal metastasis was not found to be an independent prognostic factor of HCC, and among HCC patients with peritoneal metastasis, those with advanced Child-Pugh class and with uncontrolled intrahepatic HCC showed poor survival. Therefore, the maintenance of favorable hepatic function and control of intrahepatic HCC should still be emphasized in HCC patients with peritoneal metastasis.
PubMed IF 2.8
452012

제1저자 이상협 · 교신저자 김혜령

, , , , , ,
Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients.
Pathol Int. 2012;62(3):167-75.

Abstract
The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1-2 years postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35 (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases, respectively. The expression statuses of the MDR-related proteins were positively correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2 (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion. MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047). High BCRP expression in PDAC was a significant prognostic factor for early tumor recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR-related proteins are frequently expressed in PDAC, and high BCRP expression is a significant independent predictor for early recurrence and poor survival. Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in identifying a subgroup of patients with a poor prognosis.
PubMed IF 1.9 소화기내과
442012

제1저자 양효준 · 교신저자 이효석

, , , ,
Antiviral efficacy of combination therapy with entecavir and adefovir for entecavir/lamivudine-resistant hepatitis B virus with or without adefovir resistance.
J Med Virol. 2012;84(3):424-30.

Abstract
There is little clinical information on the management of hepatitis B virus (HBV) that is resistant to multiple drugs including entecavir (ETV). The present retrospective cohort study assessed the antiviral efficacy of ETV/adefovir dipivoxil (ADV) combination therapy for ETV-resistant HBV with prior lamivudine (LAM) resistance, and either with or without previous ADV resistance. The cumulative probability of achieving a virological response (undetectable serum HBV DNA) was compared by Kaplan-Meier analysis and the Breslow method. Seventeen patients with ETV-resistant HBV who were treated with ETV/ADV combination therapy for at least 6 months at a tertiary care center, were included; seven had dual resistance to ETV and LAM [ADV-r(-) group] and 10 had triple resistance to ETV, LAM, and ADV [ADV-r(+) group]. The median follow-up period was 9 months (range, 6-23). A virological response was noted in seven patients after a median of 3 months (range, 3-12) of treatment; five in the ADV-r(-) group and two in the ADV-r(+) group. The cumulative probability of a virological response was significantly higher in the ADV-r(-) group than in the ADV-r(+) group (6 months cumulative probability, 57.1% vs. 11.1%). In conclusion, ETV/ADV combination therapy led to virological responses in five of seven patients with resistance to ETV and LAM, but a significantly poorer response in patients with prior ADV resistance than in those without prior ADV resistance. Therefore, ETV/ADV combination therapy could be a useful therapeutic option for ETV- and LAM-resistant HBV without prior ADV resistance.
PubMed IF 3.7 소화기내과
432012

제1저자 허진 · 교신저자 김효수

, , , , , , , , , , ,
New method to differentiate human peripheral blood monocytes into insulin producing cells: Human hematosphere culture.
Biochem Biophys Res Commun. 2012;418(4):765-9.

Abstract
Strategy to differentiate stem cells into insulin producing cells (IPCs) in vitro has been a promising one to get cell source of β-cell replacement therapy for diabetes. It has been suggested that islets and neurons share features and nestin-positive cells could differentiate into IPCs. We have recently developed a three-dimensional culture system using human peripheral blood cells named as blood-born hematosphere (BBHS). Here we showed that most of BBHS were composed of nestin-positive cells. Under the four-stage differentiation protocol for IPCs, we plated nestin-positive BBHS onto fibronectin-coated dish. These cells form islet-like clusters and most of them expressed insulin. Pancreatic specific genes were turned on, such as transcription factors (Pdx-1, Ngn3 and Nkx6.1), genes related to endocrine function (Glut-2 and PC2) or β cell function (Kir6.2, SUR1). Furthermore islet differentiation was confirmed by dithizone (DTZ) staining to detect zinc ion which binds insulin protein within the cells. Finally, IPCs derived from BBHS showed capability to secrete insulin in response to glucose stimulation. Taken together, our novel protocol successfully induced islet-like human insulin producing cells out of BBHS. This strategy of ex vivo expansion of IPCs using BBHS provides an autologous therapeutic cell source for the treatment of diabetes.
PubMed IF 2.5 순환기내과
422012

제1저자 임수, 최형진 · 교신저자 장학철

, , , , , , , , , ,
Subclinical atherosclerosis in a community-based elderly cohort: the Korean Longitudinal Study on Health and Aging.
Int J Cardiol. 2012;155(1):126-33.

Abstract
BACKGROUND Early detection of atherosclerosis in elderly people is important because of high cardiovascular mortality. However, only few studies have evaluated the prevalence of subclinical atherosclerosis in Asian elderly people. We evaluated subclinical atherosclerosis using various methods in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA).
METHODS Subjects aged over 65 years without symptomatic chest pain were recruited for the KLoSHA in 2006 by random stratified sampling (439 men and 561 women). Anthropometrics, biochemical parameters, body composition, and abdominal fat by computed tomography (CT) were measured. Multidetector-row cardiac CT for coronary artery calcium score (CACS) and severity of stenosis, and carotid sonography for intima-media thickness (IMT) were used to detect subclinical atherosclerosis. Pulse wave velocity (PWV) and ankle-brachial index (ABI) were also measured.
RESULTS The prevalence of subclinical atherosclerosis defined by coronary stenosis >50%, CACS >100, PWV >9m/s, carotid-IMT >0.8mm, or ABI <0.9 was 17.6%, 28.1%, 37.9%, 39.2%, and 29.6%, respectively. There were significant, but modest correlations among parameters. Although male sex, diabetes mellitus, hypertension, abnormal BMI, and higher insulin resistance were associated with subclinical atherosclerosis, older age was found to be the most robust predictor after controlling for multiple factors.
CONCLUSION Our results suggest that proactive screening with multiple measurements in elderly subjects, particularly in men and those with diabetes mellitus or hypertension, may help to identify asymptomatic patient with atherosclerosis. Further studies exploring the predictive value of diagnostic tools can determine the most appropriate measurement for predicting future cardiovascular events.
PubMed IF 3.3 내분비대사내과
412012

제1저자 박효은 · 교신저자 김형관

, , , , , , , ,
Ventricular dyssynchrony of idiopathic versus pacing-induced left bundle branch block and its prognostic effect in patients with preserved left ventricular systolic function.
Am J Cardiol. 2012;109(4):556-62.

Abstract
The extent of left ventricular (LV) dyssynchrony might not be comparable between right ventricular pacing-induced left bundle branch block (RV-LBBB) and idiopathic LBBB (iLBBB), despite the morphologic analogy on the electrocardiogram. The objectives of the present study were to elucidate the differences in the LV dyssynchrony index (LVdys) between RV-LBBB and iLBBB, and to assess the prognostic implication of LV dyssynchrony. The conventional echocardiographic parameters, LVdys, and LV end-systolic wall stress were evaluated in 20 healthy volunteers and 21 patients with iLBBB and 20 with RV-LBBB with preserved LV systolic function. Three types of LVdys were evaluated: LVdys-6, LVdys-2, and LVdys-standard deviation. The patients were clinically followed up for about 3 years. The prevalence of LV dyssynchrony was not rare in those with either iLBBB or RV-LBBB, but it was more prevalent in the patients with iLBBB than in those with RV-LBBB. The patients with iLBBB had greater LVdys than those with RV-LBBB (84 ± 55 vs 55 ± 50 for LVdys-6, 51 ± 49 vs 31 ± 40 for LVdys-2, 37 ± 24 vs 24 ± 22 for LVdys-standard deviation in iLBBB vs RV-LBBB). LVdys displayed significant correlations with QRS duration, LV volumes, LV ejection fraction, LV end-systolic wall stress, and mitral inflow E/mitral annular E' velocity ratio. Multivariate logistic regression analysis showed that the LV end-diastolic volume and LV end-systolic wall stress were independent determinants of the presence of LV dyssynchrony. During follow-up, no cardiovascular death or hospitalization for heart failure was reported in either group. In conclusion, despite similarities in electrocardiographic morphology, the extent of LV dyssynchrony were greater in patients with iLBBB, with LV preload and afterload the main determinants. No association was found between the presence of LV dyssynchrony and prognosis.
PubMed IF 2.5 순환기내과
402012

제1저자 고진신/박재홍 · 교신저자 연태진

, , , , , , , , , ,
Risk factors and effects on long-term outcomes of cardiac troponin I elevation after drug-eluting stent implantation in patients with stable coronary artery disease.
Am J Cardiol. 2012;109(4):461-5.

Abstract
This study evaluated the risk factors of postprocedure cardiac troponin I (cTnI) increase and its effects on repeat revascularization and on overall clinical outcomes in patients with angina and normal preprocedural cTnI levels who underwent successful drug-eluting stent implantation. Postprocedure cTnI increase (≥0.5 ng/ml) was observed in 207 of 802 patients (25.8%). Patients with cTnI increase had more extensive coronary disease than patients without cTnI increase, which necessitated for the cTnI group more multilesion interventions and a longer total stent length. In multivariate analysis, total stent length (odds ratio 1.02, 1.01 to 1.03, p = 0.001) and use of glycoprotein IIb/IIIa inhibitors (3.07, 1.54 to 6.11, p <0.001) were identified as independent predictors of cTnI increase. During a median follow-up of 42 months, however, there were no significant between-group differences in Kaplan-Meier estimates of any repeat revascularization (24.8% vs 18.4%, hazard ratio 1.085, 0.723 to 1.627, p = 0.694) and major adverse cardiovascular events (27.0% vs 22.4%, 1.022, 0.703 to 1.485, p = 0.911). In conclusion, patients with postprocedure cTnI increase had more severe baseline coronary disease and received more complex interventional procedures. However, cTnI increase after successful drug-eluting stent implantation was not associated with an increased risk of repeat revascularization or of other adverse events.
PubMed IF 2.5 순환기내과
392012

제1저자 유수종 · 교신저자 윤정환

, , , , , , , , ,
Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition.
J Bioenerg Biomembr. 2012;44(1):101-15.

Abstract
3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs.
PubMed IF 3.7 소화기내과
382012

제1저자 심성훈 · 교신저자 허대석

, , , , , ,
Influence of chemotherapy on nitric oxide synthase, indole-amine-2,3-dioxygenase and CD124 expression in granulocytes and monocytes of non-small cell lung cancer.
Cancer Sci. 2012;103(2):155-60.

Abstract
There is no specific marker to evaluate the immuno-suppressive status of cancer patients. Several markers, such as CD124, latency-associated peptide (LAP), arginase I, indole-amine-2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), are known to be associated with immune suppression. However, there is little research regarding the change in these parameters after chemotherapy. The present study enrolled 23 chemo-naïve non-small cell lung cancer (NSCLC) patients and 19 healthy donors. From the 23 NSCLC patients, 11 post-chemotherapy samples were collected. Surface and functional markers were analyzed by flow-cytometry. The mean fluorescence intensities (MFI) of iNOS were higher and the MFI of LAP were lower in NSCLC patient than in healthy donors (P < 0.05). In a comparison of pre-chemotherapy and post-chemotherapy groups with NSCLC, the MFI of iNOS on granulocytes and monocytes and IDO on monocytes were significantly lower in the post-chemotherapy group than in the pre-chemotherapy group (P < 0.05). In a serial analysis with 10 patients who had paired samples and who showed clinical benefits from chemotherapy, the MFI of iNOS for both cell types, and of IDO and CD124 for monocytes decreased significantly after chemotherapy, compared with those before chemotherapy (iNOS, 4.79 ± 1.75 vs 2.83 ± 0.77, P = 0.005, for granulocytes and 6.15 ± 2.94 vs 2.76 ± 1.05, P = 0.005 for monocytes; IDO, 6.81 ± 3.43 vs 4.64 ± 1.55, P = 0.012 for monocytes; CD124, 2.31 ± 0.39 vs 1.94 ± 0.43, P = 0.008 for monocytes). The changes in arginase I and LAP expression were not significant. The changes in iNOS, IDO and CD124 expression were significant after chemotherapy in NSCLC. Further evaluation of the possibility of immune status monitoring using these parameters is needed.
PubMed IF 4.9 혈액종양내과
372012

제1저자 남현진 · 교신저자 방영주/오도연

, , , , , , , , ,
Evaluation of the antitumor effects and mechanisms of PF00299804, a pan-HER inhibitor, alone or in combination with chemotherapy or targeted agents in gastric cancer.
Mol Cancer Ther. 2012;11(2):439-51.

Abstract
Recently, HER2-directed treatment, such as trastuzumab, has shown clinical benefit in HER2-amplified gastric cancer. On the basis of recent studies about epidermal growth factor receptor (EGFR) or HER2-targeting agents (including gefitinib, lapatinib, and trastuzumab) in gastric cancer, the potent effects of pan-HER inhibitors targeting the HER family are anticipated. In this study, we evaluated the activity and mechanisms of PF00299804, an irreversible pan-HER inhibitor, in gastric cancer in vitro and in vivo models. PF00299804 showed significant growth-inhibitory effects in HER2-amplified gastric cancer cells (SNU216, N87), and it had lower 50% inhibitory concentration values compared with other EGFR tyrosine kinase inhibitors, including gefitinib, lapatinib, BIBW-2992, and CI-1033. PF00299804 induced apoptosis and G(1) arrest and inhibited phosphorylation of receptors in the HER family and downstream signaling pathways including STAT3, AKT, and extracellular signal-regulated kinases (ERK) in HER2-amplified gastric cancer cells. PF00299804 also blocked EGFR/HER2, HER2/HER3, and HER3/HER4 heterodimer formation as well as the association of HER3 with p85α in SNU216 cells. The combination of PF00299804 with clinically relevant chemotherapeutic agents or molecular-targeted agents including trastuzumab (an anti-HER2 monoclonal antibody), CP751871 (an IGF1R inhibitor), PD0325901 (an ERK1/2 inhibitor), and PF04691502 (a PI3K/mTOR inhibitor) produced synergistic effects. These findings indicate that PF00299804 can be used as a targeted therapy for the treatment of HER2-amplified gastric cancer through inhibition of HER family heterodimer formation and may augment antitumor efficacy of chemotherapeutic and/or molecular-targeted agents.
PubMed IF 6.9 혈액종양내과
362012

제1저자 김진원 · 교신저자 오도연

, , , , , , , , , ,
Association of oral mucositis with quality of life and symptom clusters in patients with solid tumors receiving chemotherapy.
Support Care Cancer. 2012;20(2):395-403.

Abstract
PURPOSE The study aims to determine whether or not oral mucositis (OM) during active chemotherapy in patients with solid tumors is representative of the patient's quality of life (QOL) and the suffering from adverse effects.
METHODS From October 2007 to September 2008, we prospectively enrolled 344 consecutive patients with solid tumors who initiated a new chemotherapy regimen. OM, other adverse effects, and the QOL were surveyed by face-to-face interviews and patient diaries.
RESULTS OM developed during 175 of 633 cycles (27.7%). Forty-five percent of the patients experienced OM during two cycles of chemotherapy. The QOL in patients with OM was significantly lower than patients without OM, as evaluated by the Functional Assessment of Cancer Therapy-General (70.26 ± 15.36 and 75.09 ± 13.12, respectively; p < 0.001). Specifically, the physical and emotional well-being was lower in patients with OM compared with patients without OM. Moreover, other adverse effects were more frequent in chemotherapy cycles with OM compared with chemotherapy cycles without OM (amount of food intake, activity, nausea, vomiting, fever, myalgias, and sensory neuropathy; p < 0.001, p = 0.008, p < 0.001, p = 0.001, p = 0.002, p < 0.001, and p < 0.001, respectively).
CONCLUSIONS OM represents poor QOL and is a basic symptom of symptom clusters in patients with solid tumors receiving active chemotherapy.
PubMed IF 3.4 혈액종양내과
352012

제1저자 차명진 · 교신저자 오세일

, , , ,
Thromboembolic risk evaluation in patients with atrial fibrillation using a modified CHADS(2) scoring system.
J Cardiovasc Electrophysiol. 2012;23(2):155-62.

Abstract
BACKGROUND Antithrombotic recommendations for relatively low risk patients with atrial fibrillation (AF) are not well established. Some patients with CHADS(2) score = 0 have a CHA(2) DS(2) -VASc score of 2, which indicated warfarin therapy in the latter system. We evaluated the thromboembolic risk in AF patients with a CHADS(2) score of 0 or 1.
METHODS A total of 695 patients with AF that were followed for ≥ 12 months (median 65.6 months, range 12-138 months), were analyzed retrospectively. The modified CHADS(2) score (MCS) was applied as follows. Each CHADS(2) score group was divided into 2 groups, A and B (i.e., MCS 0A vs 0B, and MCS 1A vs 1B) according to the number of nonmajor risk factors (female gender, chronic kidney disease, coronary artery disease, age 65-74 years). Group A had 0 or 1, and group B had 2 or more nonmajor risk factors.
RESULTS In patients with CHADS(2) score = 1, there were 13 thromboembolic events (0.65%/year) in 343 MCS 1A patients, and 12 thromboembolic events (1.90%/year) in 108 MCS 1B patients. Thromboembolic risk was significantly higher in the MCS 1B compared to the MCS 1A patients (P = 0.006). In 244 patients with CHADS(2) score = 0, the thromboembolic risk of MCS 0B was similar to that of MCS 0A (P = 0.095), and 26 patients had a CHA(2) DS(2) -VASc score of 2.
CONCLUSION Patients with MCS 1B had a higher thromboembolic risk than patients with MCS 1A. Antithrombotic strategies for patients with a CHA(2) DS(2) -VASc score of 2 but a CHADS(2) score of 0 need further investigation.
PubMed IF 2.4 순환기내과
342012

제1저자 오국환 · 교신저자 오윤규

, , , , , , , , ,
Outcome of early initiation of peritoneal dialysis in patients with end-stage renal failure.
J Korean Med Sci. 2012;27(2):170-6.

Abstract
Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone.
PubMed IF 3.2 신장내과
332012

제1저자 윤연이 · 교신저자 장혁재

, , , , , , , , ,
The absence of coronary artery calcification does not rule out the presence of significant coronary artery disease in Asian patients with acute chest pain.
Int J Cardiovasc Imaging. 2012;28(2):389-98.

Abstract
The absence of coronary artery calcification (CAC) has been used to as an indication to rule out significant coronary artery disease (CAD). However, diagnostic usefulness of 'zero calcium score criteria' as a decision-making strategy to rule out significant CAD as the etiology of acute chest pain has not been studied in depth, especially in Asian ethnicity. We prospectively enrolled 136 Korean patients (58% men, 56 ± 13 years) who presented to the emergency department (ED) with acute chest pain and non-diagnostic ECG. All patients underwent 64-slice CT for calcium scoring and coronary CT angiography (cCTA). We investigated the association of CAC with the presence of ≥50% CAD on cCTA and with a final diagnosis of an acute coronary syndrome (ACS). Ninety-two patients out of 136 (68%) did not show detectable CAC, and 14 out of these 92 without CAC (15%) had ≥50% CAD on cCTA. Sensitivity, specificity, positive predictive value and negative predictive value of zero calcium score criteria for the detection of ≥50% CAD were 0.66 (95% confidence interval, 0.50-0.80), 0.83 (0.74-0.90), 0.64 (0.48-0.77), 0.85 (0.75-0.91), respectively. Patients who had ≥50% CAD without detectable CAC were younger (P = 0.001), and had a higher prevalence of smoking (P = 0.048) as compared to patients with a degree of CAC. Most of the patients with ≥50% CAD of non-calcified plaque were younger than 60 years of age (79%, 11/14), however, 3 of them were older than 60 years of age. Forty-five patients (33%) were subsequently diagnosed as having ACS, and 38% (17/45) of them had no CAC. Zero calcium score did not necessarily guarantee the absence of significant CAD, even in patients older than 60 years, in Asian ethnicity presenting to the ED with chest pain.
PubMed IF 1.5 순환기내과
322012

제1저자 김달래 · 교신저자 이춘택

, , , , , , , , ,
Combination therapy of conditionally replicating adenovirus and histone deacetylase inhibitors.
Int J Mol Med. 2012;29(2):218-24.

Abstract
Combination therapy of adenoviral gene therapy and a histone deacetylase (HDAC) inhibitor is important due to the enhancing effect of HDAC inhibitors on adenoviral transduction and transcription. However, contradictory results have been reported on the effect of combination of CRAd (conditionally replicating adenovirus) and HDAC inhibitors. This study was designed to investigate the interaction of CRAd and HDAC inhibitors and determine the ideal way to combine the two agents. Combination of HDAC inhibitors (SK7041, SBHA and vorinostat) at pre- and post-transductional periods with CRAd enhanced the transduction of CRAd and expression of luciferase expression from Δ24-luc in vitro. However, suppression of luciferase expression from Δ24-luc injected tumor mass was observed by in vivo tumor bioluminescence imaging and drug interaction analysis also showed an antagonistic interaction that was probably related with the inhibitory effect of the HDAC inhibitor on adenoviral replication. Suppression of p21 induction by p21 siRNA reversed the suppressive effect of vorinostat on the replication of CRAd, but still failed to reverse the antagonistic interaction. Addition of vorinostat at the pre-transductional period revealed an improvement in the transduction efficiency of CRAd and also induced a synergistic interaction between CRAd and vorinostat, which was possibly related with prevention of the suppressive effect of vorinostat on adenoviral replication. In conclusion, the addition of HDAC inhibitor before CRAd injection showed synergistic antitumor effects, which warrants further investigation on the sequence of HDAC inhibitor and CRAd treatment in an animal tumor model.
PubMed IF 8.5 호흡기내과
312012

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , ,
Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans.
Cardiovasc Ther. 2012;30(1):5-11.

Abstract
INTRODUCTION High posttreatment platelet reactivity to clopidogrel (HPPR) is associated with major adverse cardiac events. However, the clinical predictors of HPPR in Asians have not been studied previously.
AIMS We sought to determine clinical predictors of HPPR in Koreans.
RESULTS We measured platelet reactivity with the VerifyNow P2Y12 assay in 1431 consecutive patients undergoing coronary angiography. We used the cut-off value of greater than 275 P2Y12 Reaction Unit (PRU) to define patients with HPPR. The clinical characteristics were compared between patients with HPPR (36.3%) and those without HPPR (63.7%). The mean age (65.4 ± 9.1 vs. 62.2 ± 9.7 years) was higher, hypertension (68.5% vs. 62.0%), diabetes mellitus (35.4% vs. 28.5%), chronic kidney disease (36.3% vs. 22.5%), renal replacement treatment (1.2% vs. 0.2%), and congestive heart failure (1.3% vs. 0.3%) were more common among patients with HPPR, while male gender (72.6% vs. 54.8%) and smoking (19.9% vs. 13.1%) were more common among non-HPPR patients. Mean glomerular filtration rate (63.5 ± 18.6 vs. 69.7 ± 16.1 mL/min/1.73 m(3) ) was lower and C-reactive protein (hs-CRP) (6.6 ± 20.5 mg/L vs. 4.2 ± 12.1 mg/L) level was higher among those with HPPR. Independent predictors of HPPR were female gender (OR 1.90, P≤ 0.001), chronic kidney disease (OR 1.51, 0 = 0.004), diabetes mellitus (OR 1.35, P= 0.024), hs-CRP ≥ 2.0 mg/L (OR 1.31, P= 0.005), and age increase in decades (OR 1.21, P= 0.002), while smoking was negative risk factor (OR 0.63, P= 0.015). The number of risk factors was linearly associated with the risk of HPPR, with most patients having one or two predictors.
CONCLUSION In Korean population, independent clinical predictors of HPPR included diabetes mellitus, increased age, female gender, chronic kidney disease, and hs-CRP ≥ 2.0 mg/L, while cigarette smoking was associated with better responsiveness. Mean platelet reactivity and HPPR prevalence steadily increased with the number of clinical predictors.
PubMed IF 2.8 순환기내과
302012

제1저자 최자향 · 교신저자 허대석

, , , , , ,
CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function.
Tumour Biol. 2012;33(1):121-9.

Abstract
Myeloid-derived suppressor cells (MDSCs) are a subpopulation of myeloid cells with immunosuppressive function whose numbers are increased in conditions such as chronic infection, trauma, and cancer. Unlike murine MDSCs defined as CD11b(+)/Gr-1(+), there are no specific markers for human MDSCs. The goal of this study was to delineate a specific human MDSCs subpopulation in granulocytes from terminal cancer patients and investigate its clinical implications. Here, we show that the CD15(+)/CD16(low) subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16(low)/CD66b(++)/CD15(+)) that have a phenotype similar to MDSCs from cancer patients, effectively suppressed both proliferation and cytotoxicity of normal T cells. Among cancer patients, T-cell proliferation was highly suppressed by granulocytes isolated from terminal cancer patients with a high proportion of CD15(+)/CD16(low) cells. Patients with low peripheral blood levels of CD15(+)/CD16(low) cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15(+)/CD16(low) also tended to have poor performance status (P = 0.05). These data suggest that CD15(+)/CD16(low) granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity.
PubMed IF 2.026 혈액종양내과
292012

제1저자 곽수헌 · 교신저자 박경수

, , , , , , , , , , , , , , ,
A genome-wide association study of gestational diabetes mellitus in Korean women.
Diabetes. 2012;61(2):531-41.

Abstract
Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P=6.65×10(-16)). A variant near MTNR1B, rs10830962, was also significantly associated with the risk of GDM (1.454; P=2.49×10(-13)). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in CDKAL1 and near MTNR1B are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes.
PubMed IF 9.3 내분비대사내과
282012

제1저자 방영주

, , , , , , , , , , , , , , , , ,
Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.
Lancet. 2012;379(9813):315-21.

Abstract
BACKGROUND D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer.
METHODS The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229).
FINDINGS 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294).
INTERPRETATION Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer.
FUNDING F Hoffmann-La Roche and Sanofi-Aventis.
PubMed IF 109 혈액종양내과
272012

제1저자 박경우 · 교신저자 박경우

, ,
Response to "Sirolimus or paclitaxel drug eluting stent in left main disease: the winner is...".
Int J Cardiol. 2012;154(2):192-3.

PubMed IF 3.3 순환기내과
262012

제1저자 권현철,한주용 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , , , , ,
Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study.
Circulation. 2012;125(3):505-13.

Abstract
BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents.
METHODS AND RESULTS We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients.
CONCLUSIONS Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.
PubMed IF 41.3 순환기내과
252012

제1저자 김경희 · 교신저자 김효수

, , , , , , , , , , , , ,
Comparison of drug-eluting versus bare-metal stent implantation in ST-elevation myocardial infarction patients with renal insufficiency: results from the national registry in Korea.
Int J Cardiol. 2012;154(1):71-7.

Abstract
INTRODUCTION It is unknown whether drug-eluting stents (DES), in comparison with bare-metal stents (BMS), improve clinical outcomes of ST-elevation myocardial infarction (STEMI) patients with renal insufficiency. We aimed to compare the clinical outcomes of BMS versus DES, as well as sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES), in STEMI patients with renal insufficiency.
METHODS From the Korea Acute Myocardial Infarction Registry, 874 STEMI patients with renal insufficiency (glomerular filtration rate < 60 ml/min) comprising 116 patients with BMS and 758 patients with DES (430 SES and 328 PES) implantation were selected. Major adverse cardiac events (MACE) within 1 year, defined as composite of all-cause mortality, nonfatal myocardial infarction and target lesion revascularization were compared. In addition to multivariate adjusted analysis, propensity analysis for stent choice was performed.
RESULTS With a median follow-up of 342 days, 116 MACE occurred. MACE was more frequent in the BMS group than in the DES group before (HR [95% CI]=2.3 [1.3-3.8]) and after propensity score matching (HR [95% CI]=2.0 [1.0-3.8]). The difference of MACE was mainly driven by a higher rate of target lesion revascularization rate in the BMS group. In comparison between SES and PES, there was no significant difference between the 2 groups in propensity score-matched populations (HR [95% CI]=0.7 [0.4-1.1]).
CONCLUSIONS In STEMI patients with renal insufficiency, DES implantation exhibits a favorable 1 year clinical outcomes than BMS implantation, however, no difference was found between SES and PES.
PubMed IF 3.3 순환기내과
242012

제1저자 박경우 · 교신저자 김효수

,
Options to overcome clopidogrel response variability.
Circ J. 2012;76(2):287-92.

Abstract
Oral antiplatelet agents targeting the platelet P2Y12 receptor are an integral component of treating patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Clopidogrel has been the most commonly used agent in this respect worldwide. However, there are certain shortcomings of clopdiogrel, the most important of which is the wide response variability of platelet inhibition. The response to clopidogrel is affected by various clinical variables, genetic variations involved in its activation, and drug-drug interactions. Therefore, clinicians are faced with challenges in situations where high inhibition of platelets is necessary and in cases where the response to clopidogrel may be suboptimal. There are various ways of overcoming the response variability and this review will focus on the practical methods available. Namely, the data and evidence regarding increasing the dose of clopidogrel, adding cilostazol to standard dual antiplatelet therapy, and switching to more recently developed agents will be covered.
PubMed IF 5.8 순환기내과
232012

제1저자 김희준 · 교신저자 임석아

, , , , , , , , , , , , , , , , ,
Clinical outcome of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment.
J Neurooncol. 2012;106(2):303-13.

Abstract
Central nerve system (CNS) metastases are a feared complication of breast cancer and are associated with poor prognosis. The purpose of this study is to investigate the clinical characteristics of CNS metastases and to clarify the prognostic factors after CNS metastases in breast cancer at a single institution over a long time period. We retrospectively reviewed the medical records of breast cancer patients diagnosed at Seoul National University Hospital from 1981 to 2009 and identified the patients who experienced CNS metastases. We collected the data, including demographics, clinico-pathologic characteristics, dates of diagnosis of original breast cancer and subsequent metastases, and date of death, and correlated the findings with the clinical outcome. A total of 400 patients were identified, of whom 17 (4.3%) were diagnosed with CNS metastases and primary breast cancer concurrently and 383 (95.7%) experienced CNS metastases subsequent to the diagnosis of primary breast cancer. Further, 318 patients (79.5%) had only brain parenchymal metastases, 30 (7.5%) had only leptomeningeal metastases, and 52 (13%) had both. After the diagnosis of CNS metastasis, 170 patients (42.5%) received systemic chemotherapy (CTx) and 143 (35.8%) received CTx after whole brain radiation therapy (WBRT). The patients with good performance status (PS), initial CNS metastasis as recurrence, absence of extracranial metastases, non-visceral extracranial metastases, longer interval from the date of primary breast cancer to the date of CNS metastasis, and CTx after WBRT and gamma-knife surgery (GKS), had better outcomes in univariate analyses. In multivariate analysis, good PS, systemic CTx after WBRT, GKS, and longer interval to CNS metastasis, were independent prognostic factors for overall survival after CNS metastases. Our results suggest that appropriate palliative systemic therapy after WBRT or GKS, and adequate palliative treatment via combined modalities are helpful for breast cancer patients, even after the detection of CNS metastases.
PubMed IF 3.4 혈액종양내과
222012

제1저자 김미영 · 교신저자 장윤석

, , , , , , , , , , , , ,
Hypersensitivity reactions to oxaliplatin: clinical features and risk factors in Koreans.
Asian Pac J Cancer Prev. 2012;13(4):1209-15.

Abstract
BACKGROUND AND AIM Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy.
METHODS Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not.
RESULTS A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant.
CONCLUSIONS The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.
PubMed IF 0.659 알레르기내과
212012

제1저자 이태진 · 교신저자 송영욱

, , , , , ,
Cost of illness and quality of life of patients with rheumatoid arthritis in South Korea.
Value Health. 2012;15(1 Suppl):S43-9.

Abstract
OBJECTIVE To estimate the cost of illness (COI) and health-related quality of life (HRQOL) of rheumatoid arthritis (RA) according to four different levels of functional severity.
METHODS A face-to-face interview survey was administered to patients with RA recruited at the Rheumatology Clinic of Seoul National University Hospital. Direct costs (medical costs [treatment, drug, private physiotherapy, traditional Chinese medicine, other alternative medicine], nonmedical costs [travel, dietary supplements, auxiliary device, home assistance]), indirect costs (productivity loss due to job loss and sick leave), and deterioration in the HRQOL of patients with RA were measured. Factors associated with the COI and the HRQOL were analyzed by using multiple regression and multivariate logistic regression.
RESULTS A total of 196 patients were enrolled for this study. As RA functional severity worsened, the total costs increased accordingly (class I: 4,230,204 Korean won, class II: 7,250,674 Korean won, class III: 8,046,434 Korean won, class IV: 8,206,215 Korean won). Direct costs also increased with the severity of the functional status, with a sharp decrease in class IV. The average HRQOL score was 0.49, showing an evident impact of RA severity (class I: 0.67, class II: 0.50, class III: 0.29, class IV: 0.23). Functional class and comorbidity were significant determinants of the COI and the HRQOL.
CONCLUSION Functional severity was a major factor associated with higher COI and lower HRQOL scores. Therefore, preventing the aggravation of functional severity is crucial for decreasing the COI and improving the HRQOL of patients with RA.
PubMed IF 6.2 류마티스내과
202012

제1저자 고영일 · 교신저자 김인호

, , , , , , , , ,
Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine blood levels and clinical outcomes in patients who receive allogeneic hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant. 2012;18(1):37-43.

Abstract
In patients who received allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the correlations between single nucleotide polymorphisms (SNPs) in genes that regulate cyclosporine metabolism and clinical outcomes. All patients received sibling-matched HSCT. DNA samples of patients and donors were analyzed for 4 SNPs: MDR1 +1236C>T (rs1128503), +2677G>T>A (rs2032582), +3435C>T (rs1045642), and CYP3A5 +6986G>A (rs776746). A total of 156 patients (median age 40 years) were analyzed. Nineteen patients received HSCT for nonmalignant disease. The CYP3A5 +6986AA genotype was associated with a high cyclosporine blood level after transplantation. However, this genotype was not related to any particular clinical outcome. In contrast, the MDR1 +1236C>T SNP was correlated with specific clinical outcomes. When neither the donor nor the recipient had the CC genotype of MDR1 +1236, patients had lower creatinine levels (P < .001) and less transplantation-related mortality (TRM) (P = .012). These patients also showed longer overall survival (OS) in both univariate (P = .003) and multivariate (P = .003) analyses. Although the CYP3A5 +6986AA genotype was correlated with a high blood cyclosporine concentration, lack of the MDR1 +1236CC genotype in both the donor and recipient was correlated with less TRM and a longer OS in patients who received allogeneic HSCT.
PubMed IF 3.275 혈액종양내과

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