Thienopyridine reloading in clopidogrel-loaded patients undergoing percutaneous coronary interventions: The PRAISE study

Guo, Long Zhe,Kim, Moo Hyun,Shin, Eun Seok,Ann, Soe Hee,De Jin, Cai,Cho, Young-Rak,Park, Jong Sung,Park, Kyungil,Park, Tae-Ho,Lee, Michael S.,Serebruany, Victor L. Elsevier 2016 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.222 No.-

<P><B>Abstract</B></P> <P><B>Objective</B></P> <P>The impact of thienopyridine reloading on clinical outcomes, and residual high platelet reactivity (HPR) is unclear. We sought to compare the HRP-related effect of prasugrel and clopidogrel reloading in the already clopidogrel-loaded patients undergoing percutaneous coronary intervention (PCI).</P> <P><B>Materials and methods</B></P> <P>In this prospective, two-center, randomized, open-label study, patients with HPR who had undergone PCI after a clopidogrel (300–600mg) loading dose (LD) were enrolled. Among screened (n=153), HPR was determined in seventy-six patients, who were randomized to either repeated clopidogrel (300mg LD, followed by 75mg MD daily) or prasugrel (20mg LD, followed by 5mg MD daily). The primary endpoint was HPR at 24h after PCI, as determined by the VerifyNow assay. The rates of sustained high and low platelet reactivity, periprocedural myocardial injury (PMI) and 30-day clinical outcomes were also assessed.</P> <P><B>Results</B></P> <P>Higher inhibition of platelet reactive units (PRU) was observed in the prasugrel group than after clopidogrel reloading (Pre-PCI: 284.4±32.0 vs 279.5±32.5, p=0.504; Post-PCI: 100.0±67.0 vs 202.9±65.8, p<0.001; 30days: 170.8±69.8 vs 215.1±62.4, p=0.007). There were less HRP post-PCI after prasugrel compared with the clopidogrel group (2.7 vs 36.1%, p<0.001). However, reloading with prasugrel did not reduce PMI compared to clopidogrel (36.8% vs 39.5%, p=0.813).</P> <P><B>Conclusion</B></P> <P>Prasugrel reloading led to a greater reduction in HPR, but similar with clopidogrel PMI in post-PCI patients. Larger randomized evidence is needed for optimization of loading strategies with thienopyridines.</P> <P>Clinical Trial Registration Information: NCT01609647.</P>

Comparison of Three Tests to Distinguish Platelet Reactivity in Patients with Renal Impairment during Dual Antiplatelet Therapy

Guo, Long Zhe,Kim, Moo Hyun,Kim, Tae Hyung,Park, Jong Seong,Jin, Enze,Shim, Chang Heon,Choi, Sun Young,Serebruany, Victor L. S. Karger AG 2016 Nephron Vol.132 No.3

<P>Background: Clopidogrel and aspirin combination remains a cornerstone for modern dual antiplatelet therapy (DAPT) following coronary stenting. Although monitoring is not currently recommended, certain high-risk cohorts may benefit from tailoring antiplatelet options to reduce thrombotic or/and hemorrhagic risks. Patients with diminished estimated glomerular filtration rate (eGFR) are prone to both vascular occlusions and bleeding events in whom monitoring may be especially advantageous. We compared the residual platelet reactivity assessed by 3 conventional tests during the maintenance antiplatelet therapy dependent on eGFR. Methods: Post-stenting patients (n = 701) receiving aspirin 100 mg/ daily and clopidogrel 75 mg/daily were prospectively enrolled in the cross-sectional single-center study. Patients were dichotomized into 5 groups: eGFR >90, 60-89, 30-59, <30 ml/min/1.73 m(2), and dialysis. Platelet reactivity by VerifyNow (TM), light transmittance aggregometry (LTA), and Multiplate analyzer by multiple electrode platelet aggregometry (MEA) assays together with eGFR calculations were done simultaneously at 1 month after coronary stenting. Results: VerifyNow assay distinguished residual platelet reactivity dependent on eGFR deterioration (191 +/- 72 vs. 216 +/- 78 vs. 248 +/- 80 vs. 264 +/- 70 vs. 317 +/- 96 PRU; p < 0.001). In contrast, LTA (34.3 +/- 18.1 vs. 34.7 +/- 18.1 vs. 38.0 +/- 16.6 vs. 33.0 +/- 17.3 vs. 34.1 +/- 29.3%; p = 0.242), or MEA (37.2 +/- 19.6 vs. 33.8 +/- 18.4 vs. 38.6 +/- 21.4 vs. 36.5 +/- 20.5 vs. 38.3 +/- 28.3 AU/min; p = 0.086) failed to triage platelet reactivity in renal patients. Agreement among assays to identify patients with impaired platelet reactivity and eGFR during antiplatelet therapy was low. The multivariable regression analyses confirmed the VerifyNow advantage, since the differences in the platelet reactivity were highly significant for all renal impairment (RI) groups. In contrast, LTA did not distinguish RI patients, and for the MEA, only RI5 (dialysis) cohort exhibit borderline significant decline of residual platelet reactivity. Conclusion: Among 3 assays, VerifyNow was capable to reliably triage residual platelet reactivity in post-stenting DAPT patients dependent on the gradual decline of eGFR during therapy with clopidogrel and aspirin. These data should be confirmed in a large validation longitudinal trial, and may justify future platelet activity monitoring for potential regimen/dose adjustment in high-risk patients. The clinical implications of these data are still unclear, but may give an indication as to whether or when DAPT dose adjustment will become a reality. (C) 2016 S. Karger AG, Basel</P>

Angio-Vasculogenic Properties of Endothelial-Induced Mesenchymal Stem Cells Derived From Human Adipose Tissue

Guo, Long Zhe,Kim, Tae-Hee,Han, Seongho,Kim, Sung-Whan UNKNOWN 2016 CIRCULATION JOURNAL Vol.80 No.4

<P>Background: Although stem cells have been regarded as a promising therapeutic option, the marginal therapeutic effects of stem cells are limitations that must be overcome for the development of effective cell therapy. This study sought to identify the angio-vasculogenic properties of endothelial differentiated mesenchymal stem cells (MSCs) and to determine whether these cells are effective for vascular repair. Methods and Results: Adipose MSCs were cultured for 10 days under endothelial cell (EC) culture conditions. These endothelial cell differentiated adipose MSCs (EA) and undifferentiated adipose MSCs (UA) were characterized via angiogenesis and adhesion assays. These cells were transplanted into a hindlimb ischemia (HLI) model to determine therapeutic effects and their underlying mechanisms. EA displayed low adhesion and angiogenic properties in vitro compared with UA. When implanted into mouse HLI models, EA exhibited the decreased recovery of blood perfusion in limb ischemia than uncultured UA. Histology data showed that injected EA exhibited lower retention, angiogenic cytokine levels, and neovascularization in vivo than did UA. Short-term differentiated EA display less cell engraftment and angio-vasculogenic potential, and are less effective for peripheral vascular repair than UA. Conclusions: EC differentiation of MSCs may not present an effective strategy for the promotion of therapeutic neovascularization.</P>

Shen-Kang protects against tacrolimus-induced renal injury

Long Ye Zhang,Jian Jin,Kang Luo,Shang Guo Piao,Hai Lan Zheng,Ji Zhe Jin,임선우,최범순,양철우,Can Li 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5

Background/Aims: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. Methods: Rats were treated daily with TAC (1.5 mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. Results: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/ Bcl2-associated X [Bcl-2/Bax] ratio). Conclusions: SK protects against TAC-induced renal injury.

Synchronous tele-ultrasonography is helpful for a naive operator to perform high-quality thyroid ultrasound examinations

Xiao-Long Li,Yi-Kang Sun,Qiao Wang,Zi-Tong Chen,Zhe-Bin Qian,Le-Hang Guo,Hui-Xiong Xu 대한초음파의학회 2022 ULTRASONOGRAPHY Vol.41 No.4

Purpose: This study investigated the value of synchronous tele-ultrasonography (TUS) for naive operators in thyroid ultrasonography (US) examinations.Methods: Ninety-seven patients were included in this prospective, parallel-controlled trial. Thyroid scanning and diagnosis were completed by resident A independently, resident B with guidance from a US expert through synchronous TUS, and an on-site US expert. The on-site expert’s findings constituted the reference standard. Two other off-site US experts analyzed all data in a blind manner. Inter-operator consistency between the two residents and the on-site US expert for thyroid size measurements, nodule measurements, nodule features, American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories, and image quality was compared. Two questionnaires were completed to evaluate the clinical benefit.Results: Resident B detected more nodules consistent with the on-site expert than resident A did (89.4% vs. 56.5%, P<0.001). Resident B achieved excellent consistency with the on-site expert in terms of ACR TI-RADS categories, nodule composition, shape, echogenic foci, and vascularity (all intra-class correlation coefficients [ICCs] >0.75), while resident A achieved lower consistency in ACR TI-RADS categories, composition, echogenicity, margin, echogenic foci, and vascularity (all ICCs 0.40-0.75). Residents A and B had excellent consistency in target nodule measurements (all ICCs >0.75). Resident B achieved better performance than resident A for gray values, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (all P<0.05). Furthermore, 61.9% (60/97) of patients accepted synchronous TUS, and 59.8% (58/97) patients were willing to pay for it.Conclusion: Synchronous TUS can help inexperienced residents achieve comparable thyroid diagnostic capability to a US expert.

Lower Loading Dose of Prasugrel Compared with Conventional Loading Doses of Clopidogrel and Prasugrel in Korean Patients Undergoing Elective Coronary Angiography: A Randomized Controlled Study Evaluating Pharmacodynamic Efficacy

이동현,김무현,Long Zhe Guo,박민규,이소정 대한심장학회 2014 Korean Circulation Journal Vol.44 No.6

Background and Objectives: Although prasugrel allows for rapid and potent platelet inhibition, the efficacy and safety of lower doses of prasugrel for patients of East Asian ethnicity has not yet been investigated. We compared the effect of a lower loading dose (LD) of prasugrel with conventional LDs of clopidogrel and prasugrel in Korean patients. Subjects and Methods: Forty-three Korean patients undergoing coronary angiography were enrolled in the study. Participants were randomly administered LDs of clopidogrel 600 mg, prasugrel 30 mg or prasugrel 60 mg prior to coronary angiography. Platelet reactivity was assessed at baseline and at the time of peak platelet inhibition using light transmission aggregometry (LTA), the VerifyNow assay, and multiple electrode aggregometry. Results: Although baseline platelet reactivity between the groups showed no significant differences, at the time of peak platelet inhibition, the prasugrel 30 mg (18.9±10.0%) and 60 mg groups (13.8±10.8%) showed significantly more potent platelet inhibition than the clopidogrel 600 mg group (52.9±15.8%; p<0.001) by LTA. However, there were no significant differences between the prasugrel 30 mg and 60 mg groups (p=0.549). Conclusion: The loading effect of prasugrel 30 mg was more potent than clopidogrel 600 mg and was not significantly different from prasugrel 60 mg.

Linear Distribution Principle for Sheet Forming Using Continuous Roll Forming Process

Mi Wang,Guo-long Lu,Zhong-Yi Cai,Shu-chen Yang,Ming-Zhe Li 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.4

Continuous roll forming (CRF) process utilizes two reconfi gurable rollers as forming tools to manufacture 3D surface part. Inorder to investigate the longitudinal deformation of 3D curved surface part, the detailed mathematical methodology using ageometrical relationship is analyzed and described. The results show that the necessary condition for generating longitudinalbending deformation is the linear distribution of the longitudinal fi ber. The deformation characteristics of CRF studied bysimulation confi rm that the ideal longitudinal deformation is generated when the distribution of longitudinal fi bers satisfythe linear distribution principle, the maximum length diff erence of longitudinal fi bers is the major factor determining thelongitudinal curvature radius of formed part, and increasing maximum length diff erence of longitudinal fi bers incurs anincreasing longitudinal curvature. In addition, 3D surface parts with diff erent longitudinal curvature were prepared by CRFprocess, which had verifi ed the proposed linear distribution principle.

Correlation Between the CYP2C19 Phenotype Status and the Results of Three Different Platelet Function Tests in Cardiovascular Disease Patients Receiving Antiplatelet Therapy: An Emphasis on Newly Introduced Platelet Function Analyzer-200 P2Y Test

Shuhua Li,최재임,Long Zhe Guo,Ri-Young Goh,김보람,우광숙,김무현,한진영 대한진단검사의학회 2016 Annals of Laboratory Medicine Vol.36 No.1

Background: An association has been reported between CYP2C19 polymorphism and the altered antiplatelet activity of clopidogrel. We investigated this association using the newly introduced platelet function analyzer (PFA)-200 (INNOVANCE PFA-200 System; Siemens Healthcare, Germany) P2Y test. Methods: Polymorphisms of CYP2C19*2, *3, *17 and the degree of inhibition of platelet function were determined in 83 patients. Three different platelet function tests were used to evaluate the degree of platelet inhibition and to check the association with genotype. Results: The post-procedure PFA-200 values of extensive metabolizers (EM) patients (285.3±38.8) were higher than those of intermediate metabolizers (IM) and poor metabolizers (PM) patients (227.7±98.3 and 133.7±99.2, respectively; P=0.024). Light transmittance aggregometry (LTA) and the VerifyNow system showed that the post-procedure values for EM patients were lower than those of IM and PM patients (LTA: 24.4±15.7, 34.1±17.6, and 42.2±16.9, respectively, P<0.001; VerifyNow: 133.2±60.5, 171.5±42.6, and 218.7±59.3, respectively, P<0.001). The high residual platelet reactivity (HPR) rates were significantly different among the EM, IM, and PM groups using PFA-200 (PM:IM:EM=82.4:40.6:11.8, P<0.001). Conclusions: Approximately, 59.0% of Korean patients with cardiovascular disease receiving clopidogrel had CYP2C19 loss-of-function genotypes classified as IM or PM, and the frequency was similar to the data from Asian people. The PFA-200, LTA, and VerifyNow platelet function tests revealed evidence of a significant association between the efficacy of clopidogrel and CYP2C19 genotypes.

GW27-e0575 Impact of Renal Impairment on Platelet Reactivity and Clinical Outcomes During Chronic Dual Antiplatelet Therapy Following Coronary Stenting

Kim, Moo Hyun,Guo, Long Zhe,Shim, Chang Heon,Choi, Sun Young,Serebruany, Victor L. Elsevier 2016 JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY - Vol.68 No.16

Comparison of Prasugrel and Ticagrelor Antiplatelet Effects in Korean Patients Presenting With ST-Segment Elevation Myocardial Infarction.

Lee, Young Seok,Jin, Cai De,Kim, Moo Hyun,Guo, Long Zhe,Cho, Young-Rak,Park, Kyungil,Park, Jong Sung,Park, Tae-Ho,Kim, Young Dae Japanese Circulation Society 2015 CIRCULATION JOURNAL Vol.79 No.6

<P>There is insufficient data on the efficacy of prasugrel and ticagrelor in Korean patients with ST-segment elevation myocardial infarction (STEMI).</P>