Jin Won Kim

Harvard Medical School, Boston, Massachusetts, United States

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Publications (431)1733.69 Total impact

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    ABSTRACT: Aurivillius phase Bi7Fe3(Ti3 − xWx)O21 + δ (x = 0 and 0.06) thin films were deposited on Pt(1 1 1)/Ti/SiO2/Si(1 0 0) substrates by using a chemical solution deposition method. The W6+-ion doped Bi7Fe3Ti3O21 thin film exhibited tremendous improvements in the electrical and multiferroic properties, namely a low leakage current density, good stability against electrical breakdown, large ferroelectric polarization and large magnetization as compared to the un-doped thin film. The Bi7Fe3(Ti2.94W0.06)O21 + δ thin film was stable against electrical break down at applied electric fields up to 1275 kV/cm, at which the measured remnant polarization (2Pr) and the coercive field (2Ec) values were 33.5 μC/cm2 and 825 kV/cm, respectively whereas, the measured 2Pr value of the un-doped Bi7Fe3Ti3O21 thin film was 3.5 μC/cm2 at an applied electric field of 318 kV/cm. Furthermore, the Bi7Fe3(Ti2.94W0.06)O21 + δ thin film showed a well-saturated ferromagnetic hysteresis loop with large magnetization at room temperature.
    Applied Surface Science 08/2015; 346. DOI:10.1016/j.apsusc.2015.04.020 · 2.54 Impact Factor
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    ABSTRACT: High purity sodium hydroxide (NaOH) solution is extremely important in the large-scale manufacturing of impurity-free silicon (Si) wafers for solar cells. In this paper, we demonstrate the purification of highly concentrated NaOH via electrowinning. By optimizing temperature, current density, and the type of electrode for both anodes and cathodes, we maximized the selectivity toward cathodic deposition of Fe and Ni. Our results suggest that removal of metal impurities in the concentrated 50 wt.% NaOH is highly dependent on the reactor temperature (>90 °C) due to enhanced reaction kinetics and decreased solution viscosity. Meanwhile, current density has limited effect on the metal removal efficiency. We further demonstrate that the cathodic deposition of Fe and Ni strongly relies on the type of electrode pair used, with platinum (Pt) and nickel (Ni) as the anode and cathode, respectively, exhibiting the best removal performance. The good electrochemical performance arises from the high catalytic activity of Pt anode and good stability of Ni cathode from the highly corrosive concentrated alkaline conditions. Following these results, we recommend future scientific and technical studies on the use of electrowinning as a possible alternative to the costly membrane-based purification techniques.
    Separation and Purification Technology 05/2015; 145. DOI:10.1016/j.seppur.2015.02.011 · 3.07 Impact Factor
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    ABSTRACT: A graphene-based cathode design for lithium-sulfur batteries (LSB) that shows excellent electrochemical performance is proposed. The dual-layered cathode is composed of a sulfur active layer and a polysulfide absorption layer, and both layers are based on vitamin C treated graphene oxide at various degrees of reduction. By controlling the degree of reduction of graphene, the dual-layered cathode can increase sulfur utilization dramatically owing to the uniform formation of nanosized sulfur particles, the chemical bonding of dissolved polysulfides on the oxygen-rich sulfur active layer, and the physisorption of free polysulfides on the absorption layer. This approach enables a LSB with a high specific capacity of over 600 mAh gsulfur (-1) after 100 cycles even under a high current rate of 1C (1675 mA gsulfur (-1) ). An intriguing aspect of our work is the synthesis of a high-performance dual-layered cathode by a green chemistry method, which could be a promising approach to LSBs with high energy and power densities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    ChemSusChem 04/2015; DOI:10.1002/cssc.201500111 · 7.12 Impact Factor
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    ABSTRACT: This is a phase I/II study of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with metastatic or recurrent gastric cancer. Phase I part with a standard 3 + 3 dose-escalation design was conducted to define the recommended phase II dose (RP2D) using four predefined dose levels of paclitaxel and irinotecan. The efficacy of RP2D was evaluated in a phase II part. In phase I part, 12 patients were enrolled. Dose-limiting toxicity was not observed. The RP2D was established as level 4 (paclitaxel-135 mg/m(2) and irinotecan-160 mg/m(2), every 3 weeks). In phase II part, 27 patients were enrolled. Thirty patients, including three patients at dose level 4 in the phase I part, were analyzed for efficacy. There was no complete response. Partial response and stable disease were reported in four and 16 patients, respectively (response rate 13.3 %, 95 % CI 0.0-25.5 %; disease control rate 66.6 %, 95 % CI 49.0-83.0 %). The median time to progression and overall survival was 3.0 months (95 % CI 1.8-4.2) and 10.1 months (95 % CI 6.6-13.6), respectively. Grade 3/4 toxicities included neutropenia (2 patients, 7.4 %), thrombocytopenia (1, 3.7 %), neutropenic fever (1, 3.7 %), and diarrhea (1, 3.7 %). There were no treatment-related deaths. The RP2D of the paclitaxel and irinotecan combination is paclitaxel (135 mg/m(2)) and irinotecan (160 mg/m(2)), every 3 weeks. This combination as a second-line treatment for advanced gastric cancer shows tolerable toxicity and modest efficacy.
    Cancer Chemotherapy and Pharmacology 04/2015; DOI:10.1007/s00280-015-2732-9 · 2.57 Impact Factor
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    ABSTRACT: Lipoprotein(a) [Lp(a)] is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DESs were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) <50 mg/dl (n=485 patients), and Lp(a) ≥ 50 mg/dL (n=111 patients). Six-to-9 months angiographic outcomes and 3-year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in high Lp(a) group and 43 of 550 lesions (7.9%) in low Lp(a) group (p=0.001). In multivariate analysis, the reference vessel diameter, low dense lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In Cox proportional hazards regression analysis, Lp(a)>50 mg/dL was significantly associated with the 3-year adverse clinical outcomes including any myocardial infarction, revascularization [target lesion revascularization (TLR) and target vessel revascularization (TVR)], TLR-major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DESs was significantly associated with binary restenosis and 3-year adverse clinical outcomes in Asian population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical and Experimental Pharmacology and Physiology 04/2015; DOI:10.1111/1440-1681.12396 · 2.41 Impact Factor
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    ABSTRACT: Critical limb ischemia (CLI) is associated with a high risk of cardiovascular ischemic events. We assessed the strategy of routine coronary angiography and subsequent coronary revascularization, if clinically indicated, in patients with CLI who underwent percutaneous transluminal angioplasty (PTA). Of a total 286 consecutive CLI patients treated by PTA, 252 patients who underwent coronary angiography before or after PTA were enrolled. Coronary artery disease (CAD) was defined as angiographic stenosis ≥50% and significant CAD as ≥70% stenosis. Of the 252 patients with CLI who underwent coronary angiography, a total of 167 patients (66.3%) had CAD and 85 patients (33.7%) did not have CAD. Patients in the CAD group were older, had a higher prevalence of diabetes and cerebrovascular disease, and had a lower mean ejection fraction. In the CAD group, of the 145 patients with significant CAD, percutaneous coronary intervention (PCI) was performed in 114 patients (78.6%). At 1 year, the CAD and non-CAD groups had no statistically significant differences in mortality (7.1% vs 4.7%; P=.45), myocardial infarction (1.1% vs 0%; P=.31), and PCI (4.7% vs 1.1%; P=.31). These outcomes were similar after the adjustment of baseline confounders. At 1 year, the CAD and non-CAD groups had similar rates of repeat PTA (16.7% vs 17.6%; P=.86), target lesion revascularization (13.7% vs 14.1%; P=.94), and amputation (19.1% vs 16.4%; P=.60). A strategy of routine coronary angiography and coronary revascularization may be a reasonable treatment option for these patients who have high risk for severe CAD. A randomized trial is needed to determine if this is the preferred strategy for CLI patients.
    The Journal of invasive cardiology 04/2015; 27(4):213-7. · 0.82 Impact Factor
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    ABSTRACT: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion. Copyright © 2015. Published by Elsevier Ireland Ltd.
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    ABSTRACT: HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in CRC cell lines. The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index. The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 M, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells. These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.
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    ABSTRACT: Peripheral arterial disease (PAD) is associated with poor outcomes. We assessed the clinical outcomes of diabetic versus non-diabetic patients with PAD who underwent peripheral transluminal angioplasty (PTA). The outcomes of 239 consecutive patients with symptomatic PAD who underwent PTA were analyzed. Restenosis and clinical outcomes were assessed at a follow-up of 2 years. Diabetic patients had a higher percentage of wound as the initial diagnosis for PTA (72.7% vs 14.2%; P<.001), chronic kidney disease (26.7% vs 6.3%; P<.01), need for dialysis (19.3% vs 3.1%; P<.01), and coronary artery disease (67.6% vs 50.7%; P=.02). Infrapopliteal PTA was more commonly performed in the diabetic group (70.4% vs 25.3%; P<.001). Diabetic patients had lower rates of angiographic follow-up at 8 months (38.6% vs 60.3%; P<.01). Diabetic patients had higher binary restenosis (54.4% vs 31.5%; P=.02) and had a trend toward a higher incidence of total occlusion (34.0% vs 19.5%; P=.08). At 2-year follow-up, the amputation rate was higher in the diabetic group (24.4% vs 1.5%; P<.001) despite PTA. Diabetic patients more frequently presented with critical limb ischemia compared with non-diabetic patients and had higher rates of restenosis and amputation at 2 years following standard PTA. Improved therapies are needed for this high-risk group of patients.
    The Journal of invasive cardiology 03/2015; 27(3):167-71. · 0.82 Impact Factor
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    ABSTRACT: Evidences suggest an association between leukocytosis and thrombotic or hemorrhagic complication in polycythemia vera (PV) and essential thrombocythemia (ET), but clinical implication is not well known. To evaluate whether leukocyte burden during follow-up is related to thrombotic or hemorrhagic events in PV and ET. We retrospectively analyzed patients with PV or ET treated at Seoul National University Bundang Hospital, Korea. Time-weighted averages of leukocytes during the follow-up period were defined as leukocyte burden and were calculated for each patient and compared between patient subgroups. In each patient with events, leukocyte burden for the 3-month period before the event was compared with that for the entire follow-up period. In 102 patients with PV or ET, 35 events (16 thrombotic, 19 hemorrhagic) occurred in 29 patients (median follow-up, 54months). Leukocyte burden were significantly higher in patients with events than in event-free patients (12,015×10(3) /μL vs. 9,567×10(3)/μL, P=0.003). The difference was more prominent in ET patients than in PV patients, and in patients with hemorrhagic events than in those with thrombotic events. In patients with events, the leukocyte burden in the pre-event period was higher than in the entire follow-up period (16,767×10(3)/μL vs. 12,015×10(3)/μL, P=0.002). In all patients, leukocyte burden during entire follow-up period of 11,000×10(3)/μL or higher was an independent risk factor for vascular events. In PV or ET patients, leukocyte burden during disease course is related to increased incidence of thrombotic or hemorrhagic events. Copyright © 2015. Published by Elsevier Ltd.
    Thrombosis Research 02/2015; DOI:10.1016/j.thromres.2015.02.023 · 2.43 Impact Factor
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    ABSTRACT: Coronary artery spasm (CAS) is known to be a risk factor of acute coronary syndrome and angina pectoris. However, there is no currently available data with larger study population regarding long-term clinical outcomes of CAS in real world clinical practice. We evaluated the prevalence of CAS and the impact of CAS on 5-year clinical outcomes in a series of Asian CAS patients documented by intracoronary acetylcholine (Ach) provocation test. A total of 1413 consecutive patients without significant coronary artery disease (CAD) who underwent Ach provocation test between Nov. 2004 and Oct. 2008 were enrolled. Significant CAS was defined as >70% of narrowing by incremental intracoronary injection of 20, 50 and 100μg. Patients were divided into two groups based on the presence of significant CAS (the non-CAS group: n=640, the CAS group; n=773). To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model. A total of 54.7% (773/1413) patients were diagnosed as CAS documented by Ach provocation test. After PSM analysis, 2 propensity-matched groups (451 pairs, n=902, C-statistic=0.677) were generated. Despite of similar incidence of individual hard endpoints including mortality, myocardial infarction and revascularization, the CAS group showed the higher trend of recurrent angina requiring follow up angiography than the non-CAS group up to 5years (HR; 1.56, 95% C.I.; 0.99-2.46, p=0.054). The prevalence of CAS was 54.7%. Although the cumulative incidence of recurrent angina requiring follow up coronary angiography seems to be increased up to 5years in CAS patients, CAS patients was not associated with major individual and composite clinical outcomes such as mortality, MI, PCI, CVA with optimal medical therapy as compared with patients without CAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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    ABSTRACT: Purpose: Chemotherapy plus trastuzumab is standard of care for HER2-positive advanced gastric cancer (AGC). However, not all patients with HER2-positive AGC seem to benefit from trastuzumab. We evaluated the association between treatment outcomes with trastuzumab and HER2-status in patients with HER2-positive AGC. Methods: We enrolled 126 patients with HER2-positive AGC treated with trastuzumab plus chemotherapy in a training cohort. HER2-immunohistochemistry (IHC, N=126), HER2/CEP17 ratio (N=66), and HER2 gene copy number (N=59) were analyzed, and the optimal values for discriminating overall survival (OS) were determined using receiver operating characteristic (ROC) curve analysis. We validated the findings from the training cohort using an independent validation cohort (N=72). Results: Patients with HER2-IHC 3+ showed significantly longer OS (29 vs. 15.3 months; p=0.025) than patients with IHC ≤ 2+. A HER2/CEP17 ratio of 4.48 was the optimal cutoff for predicting longer OS (26.9 vs. 14.7 months; p=0.027. In subgroup analysis, treatment outcomes of patients with IHC 3+ were not influenced by the level of HER2 gene amplification. However, in patients with IHC ≤ 2+, a HER2/CEP17 ratio more than 3.69 and HER2 gene copy number more than 7.75 were positive predictive factors for better outcomes with trastuzumab-based chemotherapy. These findings were confirmed in both the validation cohort and the combined cohort. Conclusion: HER2-IHC status, HER2/CEP17 ratio, and HER2 gene copy number were correlated with clinical outcomes of trastuzumab-based treatment in HER2-positive AGC. Clinical outcomes of patients with IHC ≤ 2+ were strongly dependent on the HER2/CEP17 ratio and HER2 gene copy number. Copyright © 2015, American Association for Cancer Research.
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    ABSTRACT: Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins-lipid-lowering agents with anti-thrombotic and anti-inflammatory properties-in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.
    PLoS ONE 02/2015; 10(2):e0116621. DOI:10.1371/journal.pone.0116621 · 3.53 Impact Factor
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    ABSTRACT: Disclosed is a fluidized bed atomic layer deposition device for manufacturing nanocoating particles. A fluidized bed atomic layer deposition device according to an embodiment of the present invention comprises: a fluidized bed reactor, into which particles to be coated are injected; a reaction material supply unit for supplying reaction gases for coating the particles to be coated into the fluidized bed reactor; and a vibration pump coupled to the fluidized bed reactor such that the reaction gases can move therethrough, the vibration pump giving the reaction gasses regular vibration and thereby forming a turbulence inside the fluidized bed reactor.
    Ref. No: WO 2015009038 A1, Year: 01/2015
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    ABSTRACT: CO2 sorption on the NaNO3 incorporated MgO sorbent at 573-673 K has been resulted in the formation of MgCO3, referred from the results of in-situ X-ray powder diffraction combined with FT-IR spectrum. There was no interaction between CO2 and NaNO3 incorporated MgO sorbent before the melting of NaNO3. The fraction of MgCO3 was increased significantly while the NaNO3 phase in the MgO sorbent was melted at around 580 K. Further it was demonstrated that the use of eutectic mixture having a low melting point, 496 K, 12 wt% NaNO3 and 8 wt% KNO3 impregnated on MgO lower the temperature for CO2 sorption to ca. 498 K. Therefore, it was suggested that the dissolution of CO2 in liquid metal nitrate was a critical step for the CO2 capture as Mg carbonate salts.
    Energy Procedia 12/2014; 63. DOI:10.1016/j.egypro.2014.11.027
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    ABSTRACT: Background It is unclear whether preoperative chemoradiotherapy (pCRT) increases the rate of sphincter-preserving surgery (SPS), avoiding abdominoperineal resection (APR), for the treatment of distal rectal cancer. We examined whether pCRT increases the likelihood of SPS based on changes in tumor height using pelvic magnetic resonance imaging (MRI). Methods Between January 2009 and December 2013, 105 patients underwent long-course pCRT for locally advanced distal rectal cancer (≤5 cm from the anal verge) and were included in this study. The surgical procedures were analyzed in terms of radiologic findings, including the distance from the inferior margin of tumor to the superior margin of the anorectal ring (tumor height) measured by pelvic MRI before and after pCRT. Results Eighty-six (81.9 %) patients underwent SPS. Overall clinical downstaging occurred in 48 (45.7 %) patients. Tumor height increased significantly after pCRT (from 15.0 ± 15.3 to 18.1 ± 16.9 mm, change 3.1 ± 9.7 mm, p = 0.01). The mean change in tumor height was not significantly different between patients who underwent SPS or APR (mean change 3.3 ± 9.6 vs. 2.3 ± 10.5 mm, p = 0.68). The mean change was significantly greater in the double-stapled anastomosis group than in the handsewn anastomosis group (mean change 5.6 ± 9.9 vs. −0.6 ± 8.6 mm, p = 0.02). Conclusions This was the first MRI-based longitudinal study to show that pCRT does not appear to increase the likelihood of SPS in locally advanced distal rectal cancer, although it could improve the potential of double-stapled anastomoses.
    Annals of Surgical Oncology 12/2014; DOI:10.1245/s10434-014-4286-1 · 3.94 Impact Factor
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    ABSTRACT: Although posterior wall of left atrium (LA) is known to be arrhythmogenic focus, little is known about the effect of posterior wall isolation (PWI) in patients who undergo radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (PeAF). We randomly assigned 120 consecutive PeAF patients to additional PWI [PWI (+), n=60] or control [PWI (-), n=60] groups. In all patients, linear ablation was performed after circumferential pulmonary vein isolation (PVI). Linear lesions included roof, anterior perimitral, and cavotricuspid isthmus lines with conduction block. In PWI (+) group, posterior inferior linear lesion was also conducted. Creatine kinase-MB (CK-MB) and troponin-T levels were measured 1day after RFCA. LA emptying fraction (LAEF) was assessed before and 12months after RFCA. A total of 120 subjects were followed for 12months after RFCA. There were no significant differences between two groups in baseline demographics and LA volume (LAV). The levels of CK-MB and troponin-T and procedure time were not significantly different between the groups. AF termination during RFCA was more frequently observed in PWI (+) than control (P=0.035). During follow-up period, recurrence occurred in 10 (16.7%) patients in PWI (+) and 22 (36.7%) in control (P=0.02). The change in LAEF was not significantly different between the groups. On multivariate analysis, smaller LAV and additional PWI were independently associated with procedure outcome. PWI in addition to PVI plus linear lesions was an efficient strategy without deterioration of LA pump function in patients who underwent RFCA for PeAF. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 12/2014; 181C:277-283. DOI:10.1016/j.ijcard.2014.12.035 · 6.18 Impact Factor
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    ABSTRACT: There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis. Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (P values <0.05)]. Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells [5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (P values <0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.
    Gastric Cancer 11/2014; DOI:10.1007/s10120-014-0440-5 · 4.83 Impact Factor

Publication Stats

1k Citations
1,733.69 Total Impact Points

Institutions

  • 2015
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2013–2015
    • Gwangju Institute of Science and Technology
      • School of Environmental Science and Engineering
      Gwangju, Gwangju, South Korea
    • Sungkyunkwan University
      • Department of Thoracic and Cardiovascular Surgery
      Sŏul, Seoul, South Korea
  • 2012–2015
    • Seoul National University Bundang Hospital
      Sŏul, Seoul, South Korea
    • Government of the People's Republic of China
      Peping, Beijing, China
    • Tianjin Medical University
      T’ien-ching-shih, Tianjin Shi, China
    • Kyung Hee University Medical Center
      Sŏul, Seoul, South Korea
  • 2014
    • University of Seoul
      • Department of Environmental Horticulture
      Sŏul, Seoul, South Korea
  • 2013–2014
    • Yeungnam University
      • Department of Chemistry
      Onyang, South Chungcheong, South Korea
  • 2007–2014
    • Changwon National University
      • Department of Physics
      Changnyeong, Gyeongsangnam-do, South Korea
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
  • 2005–2014
    • Korea University
      • Department of Cardiology
      Sŏul, Seoul, South Korea
  • 2002–2014
    • Ajou University
      • Department of Chemical Engineering
      Sŏul, Seoul, South Korea
  • 1995–2014
    • Seoul National University
      • • Department of Internal Medicine
      • • Department of Electrical and Computer Engineering
      Sŏul, Seoul, South Korea
  • 2008–2013
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2011–2012
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2010
    • Dongguk University
      Sŏul, Seoul, South Korea
    • Cancer Research Institute
      New York, New York, United States
    • Massachusetts General Hospital
      • Cardiovascular Research Center
      Boston, Massachusetts, United States
  • 2009
    • Chung-Ang University Hospital
      Sŏul, Seoul, South Korea