Publications by authors named "Hyun-Jong Lee"

123 Publications

Effects of deferred versus immediate stenting on left ventricular function in patients with ST elevation myocardial infarction.

Medicine (Baltimore) 2021 Jul;100(28):e26598

Division of Cardiology, Department of Internal Medicine, Sejong General Hospital, Bucheon, Republic of Korea.

Background: Previous studies have shown conflicting results on the benefits of deferred stenting (DS) in infarct size and the incidence of microvascular obstruction in patients with ST elevation myocardial infarction (STEMI). However, effect of DS on left ventricular (LV) function was not known. We aimed to evaluate whether DS improve LV function and relevant clinical outcomes after STEMI, using follow-up data from the INNOVATION study (NCT02324348).

Methods: In total, 114 patients were randomly assigned to DS group or immediate stenting (IS) group at a 1:1 ratio. LV functional remodeling indices and MACE (major adverse cardiac events: a composite of death, non-fatal MI, unplanned target vessel revascularization, or hospitalization due to heart failure) were compared between DS and IS groups.

Results: Serial echocardiographic analyses were completed in 89 subjects (78%). There were no significant changes in LV volume in either group. While LV ejection fraction and wall motion score index (WMSI) improved in both groups during follow-up, the increments were not statistically different between the 2 groups (4.3 ± 8.2 vs 3.2 ± 7.1, P = .504 for ΔLV ejection fraction; -0.16 ± 0.25 vs -0.16 ± 0.25, P = .99 for ΔWMSI). However, E/e'' was decreased and e' was increased only in the DS group (-3.31 ± 5.60 vs -0.46 ± 3.10, P = .005 for ΔE/e'; 0.77 ± 1.71 vs -0.22 ± 1.64, P = .009 for Δe'). The incidence of major adverse cardiac events was numerically lower in the DS group than in the IS group without a statistical significance at 1-year follow-up.

Conclusions: Routine DS improved LV diastolic function but not systolic function compared with IS in patients with STEMI.
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http://dx.doi.org/10.1097/MD.0000000000026598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284705PMC
July 2021

Association between polyvascular disease and clinical outcomes in patients with cardiogenic shock: Results from the RESCUE registry.

Int J Cardiol 2021 Jul 8. Epub 2021 Jul 8.

Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Clinical implications of systemic atherosclerosis in patients with cardiogenic shock (CS) remain unclear. This study investigated the association between polyvascular disease (PVD) and clinical outcome in CS patients.

Methods: A total of 1247 CS patients was enrolled from the RESCUE registry, a multicenter, observational cohort between January 2014 and December 2018. They were divided into two groups according to presence of PVD, defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, or cerebrovascular disease. Primary outcome was all-cause death during 12 months of follow-up.

Results: 136 (10.9%) patients were diagnosed with PVD. The risk of 12-month all-cause death was significantly higher in the PVD group than in the non-PVD group (54.4% versus 40.4%, adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.02-1.69, p = 0.034). There was a significant interaction between PVD and vasoactive inotropic score (VIS) (p for interaction = 0.014). Among the 945 patients with VIS <84, PVD was associated with a higher risk of 12-month all-cause death (unadjusted HR 1.77, 95% CI 1.30-2.41, p = 0.030); among the 302 patients with VIS ≥84, the incidence of 12-month all-cause death was similar between the PVD and non-PVD groups (unadjusted HR 1.03, 95% CI 0.68-1.56, p = 0.301).

Conclusions: Presence of PVD was associated with 12-month all-cause mortality in patients with CS, especially for less severe forms of CS patients with VIS <84. Clinicaltrials.govnumber:NCT02985008.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.008DOI Listing
July 2021

Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation.

Korean Circ J 2021 Jul;51(7):626-638

Department of Cardiology, Charite University Hospital Campus Benjamin Franklin, Berlin, Germany.

Background And Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy.

Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment. Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke.

Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively. Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01).

Conclusions: Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.
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http://dx.doi.org/10.4070/kcj.2020.0527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263298PMC
July 2021

Comparison of in-hospital outcomes of patients with vs. without ischaemic cardiomyopathy undergoing veno-arterial-extracorporeal membrane oxygenation.

ESC Heart Fail 2021 Jun 18. Epub 2021 Jun 18.

Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, Republic of Korea.

Aims: This study aimed to investigate differences in baseline and treatment characteristics, and in-hospital mortality according to the aetiologies of cardiogenic shock in patients undergoing veno-arterial-extracorporeal membrane oxygenation (VA-ECMO).

Methods And Results: The RESCUE registry is a multicentre, observational cohort that includes 1247 patients with cardiogenic shock from 12 centres. A total of 496 patients requiring VA-ECMO were finally selected, and the study population was stratified by cardiogenic shock aetiology [ischaemic cardiomyopathy (ICM, n = 342) and non-ICM (NICM, n = 154)]. The primary outcome of interest was in-hospital mortality. Sensitivity analyses including propensity-score matching adjustments were performed. Mean age of the entire population was 61.8 ± 14.2, and 30.8% were women. There were significant differences in baseline characteristics; notable differences included the older age of patients with ICM (65.1 ± 13.7 vs. 58.2 ± 13.8, P < 0.001), preponderance of males [258 (75.4%) vs. 85 (55.2%), P < 0.001], and higher prevalence of diabetes mellitus [140 (40.9%) vs. 39 (25.3%), P = 0.001] compared with patients in the NICM aetiology group. Patients with ischaemic cardiogenic shock were more likely to have longer shock duration before VA-ECMO implantation (518.7 ± 941.4 min vs. 292.4 ± 707.8 min, P = 0.003) and were less likely to undergo distal limb perfusion than those with NICM [108 (31.6%) vs. 79 (51.3%), P < 0.001]. In-hospital mortality in the overall cohort was 52.2%; patients with ICM had a higher unadjusted risk of in-hospital mortality [203 (59.4%) vs. 56 (36.4%); unadjusted hazard ratio, 2.295; 95% confidence interval, 1.698-3.100; P < 0.001]. There were no significant differences in the primary outcome between the two aetiologies following propensity-score matching multiple adjustments (adjusted hazard ratio, 1.265; 95% confidence interval, 0.840-1.906; P = 0.260).

Conclusions: Results of the current study indicated among patients with cardiogenic shock undergoing VA-ECMO, ischaemic aetiology does not seem to impact in-hospital mortality. These findings underline that early initiation and appropriate treatment strategies of VA-ECMO for patients with ICM shock are required.
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http://dx.doi.org/10.1002/ehf2.13481DOI Listing
June 2021

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

Circ Heart Fail 2021 Jun 15;14(6):e008141. Epub 2021 Jun 15.

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center (J.H.Y., K.H.C., T.K.P., J.M.L., Y.B.S., J.-Y.H., S.-H.C., H.-C.G.), Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.

Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality.

Results: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89-3.94], <0.001), body mass index <25 kg/m (OR, 1.52 [95% CI, 1.08-2.16], =0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44-3.23], <0.001), vasoactive-inotrope score >80 (OR, 3.55 [95% CI, 2.54-4.95], <0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88-5.95], <0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16-4.63], <0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07-2.24], =0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25-2.76], =0.002) were independent predictors for in-hospital mortality.

Conclusions: The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008141DOI Listing
June 2021

Impact of chronic total occlusion lesions on clinical outcomes in patients receiving rotational atherectomy: results from the ROCK registry.

Heart Vessels 2021 Apr 10. Epub 2021 Apr 10.

Division of Cardiology, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.

The aim of this study was to investigate the impact of chronic total occlusion (CTO) on clinical outcomes in patients with calcified coronary lesions receiving rotational atherectomy (RA). This multi-center registry enrolled consecutive patients with calcified coronary artery disease who underwent RA during percutaneous coronary intervention (PCI) from 9 tertiary centers in Korea between January 2010 and October 2019. The primary outcome was target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). A total of 583 lesions were enrolled in this registry and classified as CTO (n = 42 lesions, 7.2%) and non-CTO (n = 541 lesions, 92.8%). The CTO group consisted of younger patients who were more likely to have a history of previous percutaneous coronary intervention or coronary artery bypass graft surgery. The incidence of the primary outcome was 14.1% and 16.7% for the non-CTO group and CTO group, respectively. The primary outcomes observed in the two groups were not significantly different (log-rank p = 0.736). The 18-month clinical outcomes of the CTO group were comparable to those of the non-CTO group in multivariate analysis. About 7% of patients requiring RA have CTO lesions and these patients experience similar clinical outcomes compared with those having non-CTO lesions. Use of RA for CTO lesions was safe despite higher procedural complexity.
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http://dx.doi.org/10.1007/s00380-021-01849-4DOI Listing
April 2021

Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model.

Cytotherapy 2021 Jun 19;23(6):500-509. Epub 2021 Mar 19.

Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA; Department of Chemical and Biological Engineering, Gachon University, Seongnam-si, South Korea; VA Palo Alto HealthCare System, Palo Alto, California, USA. Electronic address:

Background Aims: Corneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs.

Methods: Human MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels.

Results: All corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels.

Conclusions: PEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries.
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http://dx.doi.org/10.1016/j.jcyt.2021.02.001DOI Listing
June 2021

Metabolite analysis and anti-obesity effects of celery seed in 3T3-L1 adipocytes.

Food Sci Biotechnol 2021 Feb 23;30(2):277-286. Epub 2021 Feb 23.

Department of Food and Nutrition, College of Health Science, Kangwon National University, Samcheok, Gangwon 25949 Republic of Korea.

Celery seeds were fractioned successively by organic solvents, and fractions were screened for their antioxidant properties. Metabolites of high antioxidative fractions were analyzed, and then anti-obesity properties and mechanisms of selected fractions were evaluated in 3T3-L1 adipocytes. Celery seed ethanol extract (CSE) and celery seed ethyl acetate fraction (CSEA) possessed higher in vitro antioxidant properties, including radical scavenging and total phenolic content, than that of hexane, butanol, and water fractions. Total of 43 and 19 metabolites were identified from CSE and CSEA, respectively, by gas chromatography-mass selective detector. Isoferulic acid and -coumaric acid were only found in CSEA. CSEA possessed higher anti-adipogenesis in the 3T3-L1 cells than CSE by decreasing adipogenic hormones, including leptin and adiponectin. Expression levels of adipocyte-related transcription factors and genes such as , , , and decreased to comparable levels of control. CSEA could be used as a natural ingredient with antioxidant and anti-obesity functionality.
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http://dx.doi.org/10.1007/s10068-020-00866-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914327PMC
February 2021

Bispecific Antibody Molecule Inhibits Tumor Cell Proliferation More Efficiently Than the Two-Molecule Combination.

Drugs R D 2021 Jun 15;21(2):157-168. Epub 2021 Mar 15.

School of Engineering Sciences in Biotechnology, Chemistry and Health, AlbaNova University Center, KTH-Royal Institute of Technology, 106 91, Stockholm, Sweden.

Background: Monoclonal antibodies (mAbs) have proved to be a valuable tool for the treatment of different cancer types. However, clinical use of an increasing number of mAbs, have also highlighted limitations with monotherapy for cancers, in particular for such with more complex mechanisms, requiring action on additional molecules or pathways, or for cancers quickly acquiring resistance following monotherapy. An example for the latter is the mAb trastuzumab, FDA approved for treatment of metastatic gastric carcinoma. To circumvent this, researchers have reported synergistic, anti-proliferative effects by combination targeting of HER2 and EGFR by trastuzumab and the EGFR-targeting mAb Cetuximab overcoming trastuzumab resistance.

Methods: Maintaining the proven functionality of trastuzumab, we have designed bi-specific antibody molecules, called AffiMabs, by fusing an EGFR-targeting Affibody molecule to trastuzumab's heavy or light chains. Having confirmed binding to EGFR and Her2 and cytotoxicity of our AffiMabs, we analyzed apoptosis rate, receptor surface levels, phosphorylation levels of receptors and associated signaling pathways as well as differentially expressed genes on transcriptome level with the aim to elucidate the mode of action of our AffiMabs.

Results: The AffiMabs are able to simultaneously bind HER2 and EGFR and show increased cytotoxic effect compared to the original trastuzumab therapeutic molecule and, more importantly, even to the combination of trastuzumab and EGFR-targeting Affibody molecule. Analyzing the mode of action, we could show that bi-specific AffiMabs lead to reduced surface receptor levels and a downregulation of cell cycle associated genes on transcriptome level.

Conclusion: Our study shows that transcriptome analysis can be used to validate the choice of receptor targets and guide the design of novel multi-specific molecules. The inherent modularity of the AffiMab format renders it readily applicable to other receptor targets.
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http://dx.doi.org/10.1007/s40268-021-00339-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206453PMC
June 2021

Differential Prognostic Implications of Vasoactive Inotropic Score for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock According to Use of Mechanical Circulatory Support.

Crit Care Med 2021 May;49(5):770-780

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objectives: To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock.

Design: A multicenter retrospective and prospective observational cohort study.

Setting/patient: The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score (< 10, 10-30, 30-90, and > 90) for the present study.

Interventions: None.

Measurements And Main Results: Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for < 10, 10-30, 30-90, and > 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up.

Conclusions: High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.
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http://dx.doi.org/10.1097/CCM.0000000000004815DOI Listing
May 2021

Electrically Conductive Micropatterned Polyaniline-Poly(ethylene glycol) Composite Hydrogel.

Materials (Basel) 2021 Jan 8;14(2). Epub 2021 Jan 8.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Hydrogel substrate-based micropatterns can be adjusted using the pattern shape and size, affecting cell behaviors such as proliferation and differentiation under various cellular environment parameters. An electrically conductive hydrogel pattern system mimics the native muscle tissue environment. In this study, we incorporated polyaniline (PANi) in a poly(ethylene glycol) (PEG) hydrogel matrix through UV-induced photolithography with photomasks, and electrically conductive hydrogel micropatterns were generated within a few seconds. The electrical conductance of the PANi/PEG hydrogel was 30.5 ± 0.5 mS/cm. C2C12 myoblasts were cultured on the resulting substrate, and the cells adhered selectively to the PANi/PEG hydrogel regions. Myogenic differentiation of the C2C12 cells was induced, and the alignment of myotubes was consistent with the arrangement of the line pattern. The expression of myosin heavy chain on the line pattern showed potential as a substrate for myogenic cell functionalization.
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http://dx.doi.org/10.3390/ma14020308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827658PMC
January 2021

Comparison of clinical outcomes between multiple antithrombotic therapy versus left atrial appendage occlusion with dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation.

PLoS One 2021 7;16(1):e0244723. Epub 2021 Jan 7.

Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea.

Background: Complex antithrombotic regimens are recommended for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation but carry high bleeding risk.

Hypothesis: We aimed to evaluate whether left atrial appendage occlusion (LAAO) with dual antiplatelet therapy (DAPT) improve clinical outcomes when compared with multiple antithrombotic therapy (MAT) in patients with AF undergoing DES implantation.

Methods: Among 475 AF patients who underwent DES, 41 patients treated by LAAO with DAPT and 434 patients on MAT were compared. MAT was defined as any combination of warfarin-based antithrombotic therapy. Among the MAT group, 34.8% were on triple antithrombotic therapy. The primary endpoint was a net adverse clinical event (NACE), a composite of cerebrovascular accident (CVA) and major bleeding. Secondary endpoints were CVA, major bleeding, major adverse cardiac and cerebral event (MACCE), MI, cardiovascular death, and all-cause death. Additional analysis between the new oral anticoagulant (NOAC)-based antithrombotic therapy group (n = 45) and the LAAO group was performed for the same endpoints. To adjust the confounding factors, inverse probability of treatment weighting (IPTW) was applied during the endpoint analysis.

Results: The LAAO group showed higher incidences of diabetes mellitus, prior CVA, higher CHA2DS2-VASc score (4.56±1.55 vs. 2.96±1.60; P<0.0001), and higher HAS-BLED score (3.24±1.20 vs. 2.13±0.75; P<0.0001). NACE occurred less frequently in the LAAO group than the MAT group at 24 months (9.4% vs. 15.3%; hazard ratio 0.274; 95% confidence interval 0.136 - 0.553; P = 0.0003), mainly driven by the reduction in major bleeding (2.4% vs. 9.3%; hazard ratio 0.119; 95% confidence interval 0.032 - 0.438; P = 0.001). The LAAO group with greater thrombotic and hemorrhagic risks showed comparable primary/secondary outcomes with the NOAC-based anti-thrombotic therapy group.

Conclusions: Among patients with AF who underwent DES implantation, the LAAO group had better net clinical outcomes for preventing CVA and major bleeding than the MAT group. Further large-scale trials including comparisons with NOACs are warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244723PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790384PMC
May 2021

Efficacy and safety of thread embedding acupuncture combined with acupuncture for chronic low back pain: A randomized, controlled, assessor-blinded, multicenter clinical trial.

Medicine (Baltimore) 2020 Dec;99(49):e22526

Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Background: Low back pain is a very common disease. Many patients with chronic low back pain (CLBP) have been treated by complementary and alternative medicine such as acupuncture (AT) treatment. A type of AT, thread embedding acupuncture (TEA), consists of a thread that can continually stimulate at the AT points and has mechanical and chemical effects. Although TEA was widely used in clinical practice, there was little evidence of its efficacy and safety for CLBP.

Methods: This clinical trial was randomized, controlled, assessor-blinded, two-armed, parallel, and conducted in multiple centers. Four Korean medical institutions recruited 38 outpatients with CLBP. The participants were randomly allocated to a treatment group (TEA combined with AT) or a control group (only AT) in a 1:1 ratio. All participants received conventional AT twice a week for 8 weeks (16 sessions) at 15 AT points (GV3 and bilateral BL23, BL24, BL25, BL26, BL40, BL60, and EX-B5) and the treatment group participants additionally received TEA once a week for 8 weeks (8 sessions) on 10 AT points in the multifidus, spinal erector, and lumbar quadrate muscles. The primary outcome measure of this study was the change of visual analog scale (VAS) from baseline (0 week) to the end of intervention (8 weeks). Secondary outcome measures included clinically relevant improvement (minimal clinically important difference) and 3% to 50% decrease on VAS, disability level (Korean version of Roland and Morris disability questionnaire), quality of life (Korean version of European quality of life 5dimension), global assessment (patient global impression of change), economic analysis, credibility test, and safety assessment.

Results: The treatment group showed a significant reduction in VAS scores when compared with the control group (-33.7 ± 25.1 vs -15.6 ± 17.0, P = .013). As for the secondary outcome measures, the treatment group showed significant difference in 50% decrease on VAS and patient global impression of change. There was no serious adverse event associated with TEA and AT.

Conclusion: This clinical trial documents the efficacy and safety of TEA combined with AT for the management of CLBP.
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http://dx.doi.org/10.1097/MD.0000000000022526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717797PMC
December 2020

Clinical Significance of Low-Flow Time in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation: Results from the RESCUE Registry.

J Clin Med 2020 Nov 7;9(11). Epub 2020 Nov 7.

Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Limited data are available on the association between low-flow time and survival in patients with in-hospital cardiac arrest (IHCA) who undergo extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated data from 183 IHCA patients who underwent ECPR as a rescue procedure. Patients were divided into two groups: patients undergoing extracorporeal membrane oxygenation as an adjunct to standard cardiopulmonary resuscitation for less than 38 min ( = 110) or for longer than 38 min ( = 73). The ECPR ≤ 38 min group had a significantly greater incidence of survival to discharge compared to the ECPR > 38 min group (40.0% versus 24.7%, = 0.032). The incidence of good neurologic outcomes at discharge tended to be greater in the ECPR ≤ 38 min group than in the ECPR > 38 min group (35.5% versus 24.7%, = 0.102). The incidences of limb ischemia ( = 0.354) and stroke ( = 0.805) were similar between the two groups, but major bleeding occurred less frequently in the ECPR ≤ 38 min group compared to the ECPR > 38 min group ( = 0.002). Low-flow time ≤ 38 min may reduce the risk of mortality and fatal neurologic damage and could be a measure of optimal management in patients with IHCA.
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http://dx.doi.org/10.3390/jcm9113588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695027PMC
November 2020

Automated Algorithm Using Pre-Intervention Fractional Flow Reserve Pullback Curve to Predict Post-Intervention Physiological Results.

JACC Cardiovasc Interv 2020 11 14;13(22):2670-2684. Epub 2020 Oct 14.

Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objectives: This study sought to develop an automated algorithm using pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) pullback recordings to predict post-PCI physiological results in the pre-PCI phase.

Background: Both FFR and percent FFR increase measured after PCI showed incremental prognostic implications. However, there is no current method to predict post-PCI physiological results using physiological assessment in the pre-PCI phase.

Methods: An automated algorithm that analyzes instantaneous FFR gradient per unit time (dFFR(t)/dt) was developed from the derivation cohort (n = 30). Using dFFR(t)/dt, the pattern of atherosclerotic disease in each patient was classified into 3 groups (major, mixed, and minor FFR gradient groups) in both the internal validation cohort with constant pullback method (n = 234) and the external validation cohort with nonstandardized pullback methods (n = 252). All patients in the validation cohorts underwent PCI on the basis of pre-PCI FFR ≤0.80. Suboptimal post-PCI physiological results were defined as both post-PCI FFR <0.84 and percent FFR increase ≤15%. From the derivation cohort, cutoffs of dFFR(t)/dt for major and minor FFR gradient were 0.035/s and 0.015/s, respectively.

Results: In validation cohorts, dFFR(t)/dt showed significant correlations with percent FFR increase (R = 0.801; p < 0.001) and post-PCI FFR (R = 0.099; p = 0.029). In both the internal and external validation cohorts, the major FFR gradient group showed significantly higher post-PCI FFR and percent FFR increase compared with those in the mixed or minor FFR gradient groups (all p values <0.001). The proportions of suboptimal post-PCI physiological results were significantly different among 3 groups (10.4% vs. 25.8% vs. 45.7% for the major, mixed, and minor FFR gradient groups, respectively; p < 0.001) in validation cohorts. Absence of major FFR gradient lesion (odds ratio: 2.435, 95% [CI]: 1.252 to 4.734; p = 0.009) and presence of minor FFR gradient lesion (odds ratio: 2.756, 95% confidence interval: 1.629 to 4.664; p < 0.001) were independent predictors for suboptimal post-PCI physiological results.

Conclusions: The automated algorithm analyzing pre-PCI pullback curve was able to predict post-PCI physiological results. The incidence of suboptimal post-PCI physiological results was significantly different according to algorithm-based classifications in the pre-PCI physiological assessment. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677).
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http://dx.doi.org/10.1016/j.jcin.2020.06.062DOI Listing
November 2020

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects.

Sci Rep 2020 10 7;10(1):16671. Epub 2020 Oct 7.

Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.

Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.
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http://dx.doi.org/10.1038/s41598-020-72978-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542443PMC
October 2020

Unnecessary PCI Attempt for Presumed CTO Which Was Revealed To Be Anomalous Coronary Arteries - Role of Coronary CT Angiography.

Heart Surg Forum 2020 Sep 15;23(5):E665-E667. Epub 2020 Sep 15.

Division of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea.

Herein, we present a brief case of anomalous coronary arteries mistaken to be chronic total occlusion. Since we first presumed the anomalous coronary arteries to be chronic total occlusion of the distal right coronary artery, percutaneous coronary intervention was attempted for the presumed lesion, but it failed. Before the second attempt of percutaneous coronary intervention, coronary computed tomography angiography revealed the coronary artery from the left anterior descending artery corresponding with the distal part of the right coronary artery without connection to the right coronary artery. Therefore, we recognized the patient had anomalous coronary arteries with no connection of the vascular wall between the main and distal segments of the right coronary artery. This case may give insights to the importance of meticulous examination of coronary computed tomography angiography imaging before chronic total occlusion percutaneous coronary intervention to avoid the unnecessary procedure.
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http://dx.doi.org/10.1532/hsf.3143DOI Listing
September 2020

Efficacy and safety of thread embedding acupuncture on knee osteoarthritis: A randomized, controlled, pilot clinical trial.

Medicine (Baltimore) 2020 Sep;99(36):e21957

Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea.

Introduction: Although there are various therapeutic methods for the treatment of knee osteoarthritis, each has its advantages and shortcomings, and a definitive treatment method is yet to be determined. This pilot study is designed to obtain basic data for a further large-scale trial as well as provide information about the feasibility of thread embedding acupuncture (TEA) with polydioxanone thread in knee osteoarthritis patients.

Methods And Analysis: This study is a clinical trial to evaluate the efficacy and safety of TEA for knee osteoarthritis. Forty participants will be recruited at the hospital and after randomization into 2 groups of 20 (experimental and control); they will be treated for 6 weeks. The experimental group will receive TEA treatment 6 times (1 time/week) in 6 weeks on 14 defined knee areas, and the control group, acupuncture treatments 12 times (2 times/week) in 6 weeks on 9 defined acupuncture points. The visual analogue scale (VAS) will be used for the primary efficacy assessment and Short-form McGill Pain Questionnaire (SF-MPQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) will be used for the secondary efficacy assessment. The follow-ups before clinical trial, 3 weeks after procedure, 6 weeks after procedure, and 4 weeks after the end of procedure will be done to compare the degree of pain with the control group, which received the acupuncture treatment.

Conclusion: The trial based on this study will provide clinical information on the efficacy and safety of TEA treatment on knee osteoarthritis.

Trial Registration Number: KCT0004844.
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http://dx.doi.org/10.1097/MD.0000000000021957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478827PMC
September 2020

Prognostic Impact of Residual Anatomic Disease Burden After Functionally Complete Revascularization.

Circ Cardiovasc Interv 2020 09 8;13(9):e009232. Epub 2020 Sep 8.

Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Korea (D.H., B.-K.K.).

Background: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization.

Methods: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86).

Results: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank =0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank =0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; =0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; =0.417).

Conclusions: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009232DOI Listing
September 2020

Differential clinical impact of chronic total occlusion revascularization based on left ventricular systolic function.

Clin Res Cardiol 2021 Feb 2;110(2):237-248. Epub 2020 Sep 2.

Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, #73, Goryeodae-ro, Sungbuk-ku, Seoul, 02841, Korea.

Background: The effect of chronic total occlusion (CTO) revascularization on survival remains controversial. Furthermore, data regarding outcome differences for CTO revascularization based on left ventricular systolic function (LVSF) are limited. The differential outcomes from CTO revascularization in patients with preserved LVSF (PLVSF) versus reduced LVSF (RLVSF) were assessed.

Methods: A total of 2,173 CTO patients were divided into either a PLVSF (n = 1661, Ejection fraction ≥ 50%) or RLVSF (n = 512, < 50%) group. Clinical outcomes were compared between successful CTO revascularization (SCR) versus optimal medical therapy (OMT) within each group. The primary endpoint was a composite of all-cause death or non-fatal myocardial infarction. Inverse probability of treatment weighting for endpoint analysis and a contrast test for comparison of survival probability differences according to LVSF were used.

Results: Patients with RLVSF had a mean 37% ejection fraction (EF) and 19% had EF < 30%. The median follow-up duration was 1,138 days. Regardless of LVSF, the primary endpoint incidence was significantly lower in patients treated with SCR [RLVSF: 29.7% vs. 49.7%, hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.36-0.62, p < 0.0001; PLVSF 7.3% vs. 16.9%, HR = 0.68, 95% CI: 0.54-0.93, p = 0.0019], which was mainly driven by a reduction in cardiac death. The difference in survival probability was greater and became more pronounced over time in patients with RLVSF than with PLVSF (1-year, p = 0.197; 3-years, p = 0.048; 5-years, p = 0.036).

Conclusions: SCR was associated with better survival benefit than OMT regardless of LVSF. The benefit was greater and became more significant over time in patients with RLVSF versus PLVSF.
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http://dx.doi.org/10.1007/s00392-020-01738-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862506PMC
February 2021

Prognostic Implications of Post-Intervention Resting Pd/Pa and Fractional Flow Reserve in Patients With Stent Implantation.

JACC Cardiovasc Interv 2020 08;13(16):1920-1933

Department of Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea. Electronic address:

Objectives: This study sought to investigate the prognostic implications of post-percutaneous coronary intervention (PCI) nonhyperemic pressure ratios compared with that of post-PCI fractional flow reserve (FFR).

Background: FFR measured after PCI has been shown to possess prognostic implications. However, the prognostic value of post-PCI nonhyperemic pressure ratios has not yet been clarified.

Methods: A total of 588 patients who underwent PCI with available both post-PCI FFR and resting distal coronary pressure-to-aortic pressure ratio (Pd/Pa) were analyzed. Post-PCI FFR and Pd/Pa were measured after successful angiographic stent implantation. The primary outcome was target vessel failure (TVF) up to 2 years, defined as a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization. Prognosis of patients according to post-PCI Pd/Pa was compared with that of post-PCI FFR.

Results: Despite angiographically successful PCI, 18.5% had post-PCI FFR ≤0.80 and 36.9% showed post-PCI Pd/Pa ≤0.92. In post-PCI Pd/Pa >0.92 group, 93.8% of patients showed post-PCI FFR >0.80. Conversely, 60.4% of patients showed post-PCI FFR >0.80 in post-PCI Pd/Pa ≤0.92 group. Although there was significant difference in TVF according to post-PCI FFR (≤0.80 vs. >0.80: 10.3% vs. 2.5%; p < 0.001) and Pd/Pa (≤0.92 vs. >0.92: 6.2% vs. 2.5%; p = 0.029), the reclassification ability of model for TVF was increased only with post-PCI FFR (net reclassification index 0.627; p = 0.003; integrated discrimination index 0.019; p = 0.015), but not with post-PCI Pd/Pa, compared with model including clinical factors. Compared with patients with post-PCI Pd/Pa >0.92, patients with post-PCI Pd/Pa ≤0.92 and FFR ≤0.80 had significantly higher risk of TVF (10.4% vs. 2.5%; adjusted hazard ratio: 4.204; 95% confidence interval: 1.521 to 11.618; p = 0.006); however, those with post-PCI Pd/Pa ≤0.92 but FFR >0.80 showed similar risk of TVF (3.5% vs. 2.5%; adjusted hazard ratio: 1.327; 95% confidence interval: 0.398 to 4.428; p = 0.645).

Conclusions: Over one-half of the patients with abnormal post-PCI Pd/Pa ≤0.92 showed post-PCI FFR >0.80. Compared with post-PCI FFR, post-PCI Pd/Pa showed limited reclassification ability for the occurrence of TVF. Among patients with abnormal post-PCI Pd/Pa, only patients with positive post-PCI FFR showed significantly higher risk of TVF than did those with post-PCI Pd/Pa >0.92. (Prognostic Perspective of Invasive Hyperemic and Non-Hyperemic Physiologic Indices Measured After Percutaneous Coronary Intervention [PERSPECTIVEPCI]; NCT04265443).
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http://dx.doi.org/10.1016/j.jcin.2020.05.042DOI Listing
August 2020

Thermoresponsive poly(N-isopropylacrylamide) hydrogel substrates micropatterned with poly(ethylene glycol) hydrogel for adipose mesenchymal stem cell spheroid formation and retrieval.

Mater Sci Eng C Mater Biol Appl 2020 Oct 26;115:111128. Epub 2020 May 26.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address:

Cell spheroid formation is necessary to develop three-dimensional (3D) cellular environments that provide appropriate cell-cell and cell-matrix interactions similar to in vivo environments without additional substrates. Although some methods including stirring culture, low adhesion plate culture, hanging drop, and microfluidics are used to construct cell spheroids, there is no method to fulfill all of the mass production of uniform spheroids, simple media change, and easy retrievability. Here, bulk poly(N-isopropylacrylamide) (PNIPAAm) hydrogel substrate (PHS) was used to fabricate, culture, and retrieve cell spheroids. Adipose-derived stem cells (ASCs) were cultured on bulk PHS to form spheroids. ASCs formed cell spheroids directly on substrates without additional manipulation. These spheroids adhered to the semi-adhesive substrate, while the spheroids fabricated using the nonadhesive surface method floated without getting fixed to the surface. Bulk PHS stiffness was evaluated using the compressive test (compressive modulus: 153 ± 11 kPa). A poly(ethylene glycol) (PEG) hydrogel microwell pattern was created on PHS to control the spheroid size, forming uniform ASC spheroids between 100 and 150 μm in diameter on 200 and 300 μm well-patterned substrates. Cell-cell interactions in the resulting ASC spheroids were evaluated based on fibronectin and laminin expression; fluorescence intensities of fibronectin- and laminin-immunostained images of ASC spheroids were 10.9 and 7.3 times higher than those of ASCs cultured on the tissue culture plate, respectively. ASC spheroids were detached following incubation at 4 °C for 10 min (retrieval efficiency: 74 ± 19%). Retrieved spheroid cell viability was over 97.5%. The PEG hydrogel microwell-patterned PHS is a convenient spheroid fabrication and retrieval platform that can increase cell spheroid usage.
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http://dx.doi.org/10.1016/j.msec.2020.111128DOI Listing
October 2020

Detection of Ferric Ions and Catecholamine Neurotransmitters via Highly Fluorescent Heteroatom Co-Doped Carbon Dots.

Sensors (Basel) 2020 Jun 19;20(12). Epub 2020 Jun 19.

Department of Chemical and Biological Engineering, Gachon University, Seongnam 13120, Korea.

Carbon dots (CDs) demonstrate very poor fluorescence quantum yield (QY). In this study, with the help of a hydrothermal method, we combined CDs with nitrogen and phosphorus elements belonging to the VA group (in the periodic table) to form heteroatom co-doped CDs, i.e., nitrogen and phosphorus co-doped carbon dots (NPCDs). These displayed a significant improvement in the QY (up to 84%), which was as much as four times than that of CDs synthesized by the same method. The as-prepared NPCDs could be used as an "off-on" fluorescence detector for the rapid and effective sensing of ferric ions (Fe) and catecholamine neurotransmitters (CNs) such as dopamine (DA), adrenaline (AD), and noradrenaline (NAD). The fluorescence of NPCDs was "turned off" and the emission wavelength was slightly red-shifted upon increasing the Fe concentration. However, when CNs were incorporated, the fluorescence of NPCDs was recovered in a short response time; this indicated that CN concentration could be monitored, relying on enhancing the fluorescence signal of NPCDs. As a result, NPCDs are considered as a potential fluorescent bi-sensor for Fe and CN detection. Particularly, in this research, we selected DA as the representative neurotransmitter of the CN group along with Fe to study the sensing system based on NPCDs. The results exhibited good linear ranges with a limit of detection (LOD) of 0.2 and 0.1 µM for Fe and DA, respectively.
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http://dx.doi.org/10.3390/s20123470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349486PMC
June 2020

Highly Selective Fluorescence Sensor Based on Graphene Quantum Dots for Sulfamethoxazole Determination.

Materials (Basel) 2020 Jun 1;13(11). Epub 2020 Jun 1.

Department of Chemical and Biological Engineering, Gachon University, Seongnam 13120, Korea.

In our research, a reliable fluorescence sensor for the detection of sulfamethoxazole (SMZ) was developed. This method relies on graphene quantum dots (GQDs) entrapped in a silica molecularly imprinted polymer ([email protected]), which was synthesized by the polymerization using GQDs, SMZ, tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) as fluorescence material, template, cross-linker, and functional monomers, respectively. The [email protected] was characterized by fluorometry, Fourier-transform infrared spectroscopy, transmission and scanning electron microscopies, X-ray photoelectron spectroscopy, and powder X-ray diffraction. The [email protected] exhibited a good capacity to absorb SMZ from solution, which resulted in the quenching of the GQD fluorescence intensity. The intensity of [email protected] decreased linearly with the SMZ concentration in the range of 1 to 100 µM with a correlation coefficient of 0.99537. In addition, the fluorescence responses of [email protected] to interfering substances were investigated. The results indicated that there was no effect of interfering substances on SMZ detection. Thus, the highly selective [email protected] fluorescence sensor is an effective and promising device for SMZ detection and analysis.
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http://dx.doi.org/10.3390/ma13112521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321422PMC
June 2020

Round Acupuncture for the Treatment of Recurrent Carpal Tunnel Syndrome.

J Pharmacopuncture 2020 Mar;23(1):37-41

Department of Acupuncture & Moxibustion medicine, College of Korean medicine, Daegu Haany University, Republic of Korea.

Objectives: Round Acupuncture having blunt end has developed from acupotomy. This case report is to find out that Round Acupuncture is effective in treating patients with recurrent carpal tunnel syndrome (CTS), which has not improved by steroid injection or acupotomy.

Methods: Round Acupuncture was inserted into the distal fibers of transverse carpal ligament and released toward the proximal fibers. Treatment was performed three times in total. T ingling, numbn ess, night pain and swelling sensation were assessed, and provocative maneuvers were also used.

Results: After treat ment, all symptoms completely disappeared and the patient had no recurrence until 3 months after treatment.

Conclusion: Round Acupuncture co uld be an effective treatment for recurrent CTS.
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http://dx.doi.org/10.3831/KPI.2020.23.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163388PMC
March 2020

Acupuncture inhibits reinstatement of intravenous methamphetamine self-administration via gamma aminobutyric acid pathway.

Neuroreport 2020 03;31(4):352-358

Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, Suseong-Gu, Daegu, Republic of Korea.

Methamphetamine is one of the widely abused drugs. Nevertheless, there is little predominant therapy for the abuse. In the previous study, acupuncture had shown to attenuate methamphetamine self-administration behavior, and based on, the present study investigated whether acupuncture inhibits the reinstatement of methamphetamine self-administration. As well, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300 g were trained to intravenously self-administer methamphetamine (0.1 mg/kg) for 3 weeks. Following training, rats who administered stable amount of methamphetamine underwent extinction period of 1 week. Thereafter, priming injection was performed to induce reinstatement, and acupuncture was given immediately before priming. In the second experiment, the selective antagonists of GABAA and GABAB receptors were treated prior to acupuncture to investigate a neuronal mechanism of GABAergic pathway. Acupuncture treatment at HT7, but not at the control acupoint LI5, reduced the active lever responses on the reinstatement session, showing that HT7 suppressed craving for methamphetamine induced by reexposure to the drug during abstinence. And, the effects of acupuncture were blocked by the GABA receptors' antagonists. In addition, HT7 did not influence saline self-administration, indicating that acupuncture effect was selective to the methamphetamine. Results of the present study show that acupuncture at HT7 suppresses reinstatement of methamphetamine self-administration behavior through the GABA receptor system without affecting the normal state. From the results, it may be suggested that acupuncture at HT7 can be a useful option in the treatment of methamphetamine addiction.
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http://dx.doi.org/10.1097/WNR.0000000000001412DOI Listing
March 2020

Efficacy, safety, and cost-effectiveness analysis of adjuvant herbal medicine treatment, Palmijihwang-hwan, for chronic low back pain: a study protocol for randomized, controlled, assessor-blinded, multicenter clinical trial.

Trials 2019 Dec 27;20(1):778. Epub 2019 Dec 27.

Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South Korea.

Background: Low back pain is a common symptom and continuous or recurrent pain results in chronic low back pain (CLBP). While many patients with CLBP have tried various treatments, complementary and alternative medicine including acupuncture and herbal medicine is one of the commonly used treatments. Palmijihwang-hwan is a herbal medicine used frequently in clinical practice but there has been no report of the efficacy, safety, or cost-effectiveness analysis of Palmijihwang-hwan for CLBP.

Methods: This study is a randomized, assessor-blinded, multicenter, clinical trial with two parallel groups. Four Korean medicine hospitals will recruit 84 participants and randomly allocate them into the control or treatment group in a 1:1 ratio. The control group will receive acupuncture treatment at 11 local and 4 distal acupuncture points for 20 min twice a week for 6 weeks. The treatment group will receive the same acupuncture treatment as the control group and also take Palmijihwang-hwan for 6 weeks. The primary outcome will be the change in visual analog scale (VAS) score between baseline (visit 1) and completion of the intervention (visit 12), and secondary outcomes will be pain-related clinical relevance (minimal clinical important difference or the proportion of the participants who decrease more than 30, or 50% on VAS), disability (Roland and Morris Disability Questionnaire), quality of life (EuroQol-5D), global assessment (Patient Global Impression of Change), and economic analysis (cost-effectiveness and cost-utility analysis). Additionally, safety will be assessed.

Discussion: The results of our study will provide the clinical evidence about the efficacy, safety, and cost-effectiveness analysis of Palmijihwang-hwan for CLBP. There will be a chance to provide multiple subdivided influence of this treatment with various outcome measures, but lack of placebo is our limitation.

Trial Registration: Clinical Research Information Service, KCT0002998. Registered on 12 July 2018.
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http://dx.doi.org/10.1186/s13063-019-3776-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935187PMC
December 2019

Thread-embedding acupuncture for lumbar herniated intervertebral disc: Protocol for a systematic review and meta-analysis.

Medicine (Baltimore) 2019 Nov;98(45):e17847

Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul, Republic of Korea.

Background: Lumbar herniated intervertebral disc (LHIVD) is a frequent disease among patients attending Korean medicine hospitals, and it is associated with considerable medical expenses for the patients. Although several recent randomized clinical trials (RCTs) have reported that thread-embedding acupuncture (TEA) has a more favorable therapeutic effect on LHIVD than other types of acupuncture or other treatments, the evidence remains limited because these trials used poor assessment methods and had a high risk of bias. This study aims to evaluate the evidence for the effectiveness and safety of TEA for LHIVD. In this article, we describe our methods and plan for a systematic review.

Methods: We will conduct an electronic search of the following databases from their inception to May 2018: MEDLINE; EMBASE; COCHRANE; China National Knowledge Infrastructure (CNKI) (a Chinese database); CiNii and J-STAGE (Japanese databases); and KoreaMed, Korean Medical Database (KMbase), Korean Studies Information Service System (KISS), National Digital Science Library (NDSL), Korea Institute of Science and Technology Information (KISTI), Oriental Medicine Advanced Searching Integrated System (OASIS). RCTs investigating any type of TEA will be included. The risk of bias in each study will be evaluated using the Cochrane risk of bias tool. Risk ratios or mean differences with 95% confidence intervals will be used to show the effects of TEA if it will be possible to conduct a meta-analysis. Sensitivity analyses will also be conducted in this study.

Ethics And Dissemination: Ethical approval is not necessary as this paper does not involve patient data. The review will be published in a peer-reviewed journal or presented in a conference.

Trial Registration Number: PROSPERO CRD42019133060.
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http://dx.doi.org/10.1097/MD.0000000000017847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855608PMC
November 2019

A comparison of procedural success rate and long-term clinical outcomes between in-stent restenosis chronic total occlusion and de novo chronic total occlusion using multicenter registry data.

Clin Res Cardiol 2020 May 24;109(5):628-637. Epub 2019 Sep 24.

Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea.

Background: There have been little data about outcomes of percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) chronic total occlusion (CTO) in the drug eluting stent (DES) era. This study aimed to compare the procedural success rate and long-term clinical outcomes of ISR CTO and de novo CTO.

Methods And Results: Patients who underwent PCI for ISR CTO (n = 164) versus de novo CTO (n = 1208) were enrolled from three centers in Korea between January 2008 and December 2014. Among a total of ISR CTO, a proportion of DES ISR CTO was 79.3% (n = 130). The primary outcome was major adverse cardiac events (MACEs); a composite of all-cause death, non-fatal myocardial infarction (MI), or target lesion revascularization (TLR). Following propensity score-matching (1:3), the ISR CTO group (n = 156) had a higher success rate (84.6% vs. 76.0%, p = 0.035), mainly driven by high success rate of PCI for DES ISR CTO (88.6%), but showed a higher incidence of MACEs [hazard ratio (HR): 2.06; 95% confidence interval (CI) 1.37-3.09; p < 0.001], mainly driven by higher prevalence of MI [HR: 9.71; 95% CI 2.06-45.81; p = 0.004] and TLR [HR: 3.04; 95% CI 1.59-5.81; p = 0.001], during 5 years of follow-up after successful revascularization, as compared to the de novo CTO group (n = 408).

Conclusion: The procedural success rate was higher in the ISR CTO than the de novo CTO, especially in DES ISR CTO. However, irrespective of successful revascularization, the long-term clinical outcomes for the ISR CTO were significantly worse than those for the de novo CTO, in terms of MI and TLR.
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http://dx.doi.org/10.1007/s00392-019-01550-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182633PMC
May 2020

Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo.

Acta Biomater 2019 11 17;99:247-257. Epub 2019 Sep 17.

Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, United States; Chemical Engineering, Stanford University, Palo Alto, California, United States; VA Palo Alto HealthCare System, Palo Alto, California, United States. Electronic address:

The therapeutic effects of secreted factors (secretome) produced by bone marrow-derived human mesenchymal stem cells (MSCs) were evaluated as a function of their growth in 2D culture conditions and on 3D electrospun fiber scaffolds. Electrospun fiber scaffolds composed of polycaprolactone and gelatin were fabricated to provide a 3D microenvironment for MSCs, and their mechanical properties were optimized to be similar to corneal tissue. The secretome produced by the MSCs cultured on 3D fiber matrices versus 2D culture dishes were analyzed using a Luminex immunoassay, and the secretome of MSCs cultured on the 3D versus 2D substrates showed substantial compositional differences. Concentrations of factors such as HGF and ICAM-1 were increased over 5 times in 3D cultures compared to 2D cultures. In vitro proliferation and scratch-based wound healing assays were performed to compare the effects of the secretome on corneal fibroblast cells (CFCs) when delivered synchronously from co-cultured MSCs through a trans-well co-culture system versus asynchronously after harvesting the factors separately and adding them to the media. Cell viability of CFCs was sustained for 6 days when co-cultured with MSCs seeded on the fibers but decreased with time under other conditions. Scratch assays showed 95% closure at 48 h when CFCs were co-cultured with MSCs seeded on fibers, while the control group only exhibited 50% closure at 48 h. Electrospun fibers seeded with MSCs were then applied to a rabbit corneal organ culture system, and MSCs seeded on fibers promoted faster epithelialization and less scarring. Corneas were fixed and stained for alpha smooth muscle actin (α-SMA), and then analyzed by confocal microscopy. Immunostaining showed that expression of α-SMA was lower in corneas treated with MSCs seeded on fibers, suggesting suppression of myofibroblastic transformation. MSCs cultured on electrospun fibers facilitate wound healing in CFCs and on explanted corneas through differential secretome profiles compared to MSCs cultured on 2D substrates. Future work is merited to further understand the nature and basis of these differences and their effects in animal models. STATEMENT OF SIGNIFICANCE: Previous studies have shown that the secretome of bone marrow-derived mesenchymal stem cells (MSC) is promotes corneal wound healing by facilitating improved wound closure rates and reduction of scarring and neovascularization. The present research is significant because it provides evidence for the modulation of the secretome as a function of the MSC culture environment. This leads to differential expression of therapeutic factors secreted, which can impact corneal epithelial and stromal healing after severe injury. In addition, this article shows that co-continuous delivery of the MSC secretome improves cell migration and proliferation over aliquoted delivery, and that MSCs grown on three-dimensional electrospun fiber constructs may provide a favorable microenvironment for cultured MSCs and as a carrier to deliver their secreted factors to the ocular surface.
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http://dx.doi.org/10.1016/j.actbio.2019.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101245PMC
November 2019
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