Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 615
Filtrar
1.
Circ J ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732599

RESUMO

Advances in nuclear reprogramming technology have enabled the dedifferentiation and transdifferentiation of mammalian cells. Forced induction of the key transcription factors constituting a transcriptional network can convert cells back to their pluripotent status or directly to another cell fate without inducing pluripotency. To date, direct conversion to several cell types, including cardiomyocytes, various types of neurons, and pancreatic ß-cells, has been reported. We previously demonstrated direct lineage reprogramming of adult fibroblasts into induced endothelial cells (iECs) in mice and humans. In contrast to induced pluripotent stem cells, for which there is consensus on the criteria defining pluripotency, such criteria have not yet been established in the field of direct conversion. We thus suggest that careful assessment of the status of converted cells using genetic and epigenetic profiling, various functional assays, and the use of multiple readouts is essential to determine successful conversion. As direct conversion does not go through pluripotent status, this technique can be utilized for therapeutic purposes without the risk of tumorigenesis. Further, direct conversion can be induced in vivo by gene delivery to the target tissue or organ in situ. Thus, direct conversion technology can be developed into cell therapy or gene therapy for regenerative purposes. Here, we review the potential and future directions of direct cell fate conversion and iECs.

3.
J Am Coll Cardiol ; 78(20): 1968-1986, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34763774

RESUMO

BACKGROUND: Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain. OBJECTIVES: The authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events. METHODS: Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES. RESULTS: In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis. CONCLUSIONS: In the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding.

4.
J Korean Med Sci ; 36(42): e268, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725976

RESUMO

BACKGROUND: Although ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown. METHODS: A total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively. RESULTS: After propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010-2.805; P = 0.046) and the KAMIR-HBR group (OR, 3.460; 95% CI, 1.374-8.714; P = 0.008). However, there was no significant difference in in-hospital TIMI major bleeding between ticagrelor and clopidogrel in the KAMIR-non HBR group (OR, 1.436; 95% CI, 0.722-2.855; P = 0.303). No differences were observed in the cumulative incidences of in-hospital and 6-month MACEs between ticagrelor and clopidogrel in both groups. CONCLUSIONS: The bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.

5.
PLoS One ; 16(10): e0258525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644362

RESUMO

BACKGROUND: A substantial number of patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) have severe left ventricular systolic dysfunction (LVSD) (left ventricular ejection fraction (LVEF) less than 35%). But data are lacking regarding optimal percutaneous coronary intervention (PCI) strategy for these patients. The aim of this study was to compare the long-term outcomes of IRA (infarct-related artery)-only and multivessel PCI in patients with NSTEMI and MVD complicated by severe LVSD. METHODS: Among 13,104 patients enrolled in the PCI registry from November 2011 to December 2015, patients with NSTEMI and MVD with severe LVSD who underwent successful PCI were screened. The primary outcome was 3-year major adverse cardiovascular events (MACEs), defined as all-cause death, any myocardial infarction, stroke, and any revascularization. RESULTS: Overall, 228 patients were treated with IRA-only PCI (n = 104) or MV-PCI (n = 124). The MACE risk was significantly lower in the MV-PCI group than in the IRA-only PCI group (35.5% vs. 54.8%; hazard ratio [HR] 0.561; 95% confidence interval [CI] 0.378-0.832; p = 0.04). This result was mainly driven by a significantly lower risk of all-cause death (23.4% vs. 41.4%; hazard ratio [HR] 0.503; 95% confidence interval [CI] 0.314-0.806; p = 0.004). The results were consistent after multivariate regression, propensity-score matching, and inverse probability weighting to adjust for baseline differences. CONCLUSIONS: Among patients with NSTEMI and MVD complicated with severe LVSD, multivessel PCI was associated with a significantly lower MACE risk. The findings may provide valuable information to physicians who are involved in decision-making for these patients.

6.
Int Heart J ; 62(5): 988-996, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544968

RESUMO

In this study, we aimed to investigate the time course of new-onset complete atrioventricular block (CAVB) and its reversibility after transcatheter aortic valve implantation (TAVI). We analyzed 206 consecutive patients without baseline CAVB who underwent successful TAVI. The incidence of new-onset CAVB was determined to be 12.6% (26/206). Among these patients, 14 recovered from CAVB within 2 weeks (6.8%, 14/206), while the remaining 12 (5.8%, 12/206) underwent permanent pacemaker (PPM) insertion. Among the 12 patients who received the PPM, 4 were able to recover from CAVB within 4 months. Thus, only 8 among 206 patients (3.8%) showed persistent CAVB. Early-onset CAVB on the day of the procedure was the strongest predictor of PPM implantation (OR = 127). The electrocardiographic changes that occurred after TAVI were mostly recovered after 1 month. The most critical procedural factor that predicts CAVB and PPM insertion is the deep implantation (>4 mm) of a big valve (oversizing index >5.9%). In conclusion, the incidence of CAVB after TAVI was estimated to be at 12.6%. Two-thirds of these patients recovered from CAVB within 3 days, resulting in a final rate of persistent CAVB of 4%. To prevent CAVB, we have to implant an appropriate valve type with an optimal size and depth.


Assuntos
Estenose da Valva Aórtica/cirurgia , Bloqueio Atrioventricular/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/terapia , Eletrocardiografia/métodos , Feminino , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Incidência , Síndrome do QT Longo , Masculino , Marca-Passo Artificial/efeitos adversos , Valor Preditivo dos Testes , Recuperação de Função Fisiológica/fisiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/instrumentação
7.
J Hematol Oncol ; 14(1): 148, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530889

RESUMO

BACKGROUND: Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. METHODS: Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. RESULTS: KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. CONCLUSIONS: KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.


Assuntos
Proteína Kangai-1/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica , Animais , Feminino , Proteína Kangai-1/genética , Masculino , Microdomínios da Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
J Am Heart Assoc ; 10(18): e021632, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34514841

RESUMO

Background Despite advances in devices and techniques, coronary bifurcation lesion remains a challenging lesion subset in the field of percutaneous coronary intervention (PCI). We evaluate 10-year trends in bifurcation PCI and their effects on patient outcomes. Methods and Results We analyzed 10-year trends in patient/lesion characteristics, devices, PCI strategy, stent optimization techniques, and clinical outcomes using data from 5498 patients who underwent bifurcation PCI from 2004 to 2015. Clinical outcomes 2 years after the index procedure were evaluated in terms of target vessel failure (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and a patient-oriented composite outcome (a composite of all-cause death, myocardial infarction, and any revascularization). During the 10-year study period, patient and lesion complexity, such as multivessel disease, diabetes mellitus, chronic kidney disease, and left main bifurcation, increased continuously (all P<0.001). The risk of target vessel failure or patient-oriented composite outcome decreased continuously from 2004 to 2015 (target vessel failure: from 12.3% to 6.9%, log-rank P<0.001; patient-oriented composite outcome: from 13.6% to 9.3%, log-rank P<0.001). The use of a second-generation drug-eluting stent and decreased target vessel failure risk in true bifurcation lesions were the major contributors to improved patient prognosis (interaction P values were <0.001 and 0.013, respectively). Conclusions During the past decade of bifurcation PCI, patient and lesion characteristics, devices, PCI techniques, and patient prognosis have all significantly changed. Despite increased patient and lesion complexity, clinical outcomes after bifurcation PCI have improved, mainly because of better devices and more widespread adoption of procedural optimization techniques and appropriate treatment strategies. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01642992 and NCT03068494.

9.
Am J Cardiol ; 156: 16-23, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34353628

RESUMO

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients.


Assuntos
Síndrome Coronariana Aguda/terapia , Stents Farmacológicos , Terapia Antiplaquetária Dupla/métodos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Sistema de Registros , Síndrome Coronariana Aguda/diagnóstico , Idoso , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
N Engl J Med ; 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34449183

RESUMO

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

11.
Am J Cardiol ; 156: 24-31, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294409

RESUMO

Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.


Assuntos
Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/métodos , Sistema de Registros , Trombose/terapia , Idoso , Angiografia Coronária , Doença da Artéria Coronariana , Terapia Antiplaquetária Dupla , Feminino , Saúde Global , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco
12.
Biomaterials ; 275: 120980, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34198163

RESUMO

We expanded the application of endothelin-1 (EDN1) by treating human mesenchymal stem cell (hMSC) organotypic spinal cord slice cultures with EDN1. EDN1-treated hMSCs significantly enhanced neuronal outgrowth. The underlying mechanism of this effect was evaluated via whole-genome methylation. EDN1 increased whole-genome demethylation and euchromatin. To observe demethylation downstream of EDN1, deaminases and glycosylases were screened, and APOBEC1 was found to cause global demethylation and OCT4 gene activation. The sequence of methyl-CpG-binding domain showed similar patterns between EDN1- and APOBEC1-induced demethylation. SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 4 (SMARC A4) and SMARC subfamily D, member 2 (SMARC D2) were screened via methyl-CpG-binding domain sequencing as a modulator in response to EDN1. Chromatin immunoprecipitation of the H3K9me3, H3K27me3, and H3K4me4 binding sequences on the APOBEC1 promoter was analyzed following treatment with or without siSMARC A4 or siSMARC D2. The results suggested that SMARC A4 and SMARC D2 induced a transition from H3K9me3 to H3K4me3 in the APOBEC1 promoter region following EDN1 treatment. Correlations between EDN1 pathways and therapeutic efficacy in hBM-MSCs were determined in a sciatic nerve injury mouse model. Thus, EDN1 may be a useful novel-concept bioactive peptide and biomaterial component for improving hMSC regenerative capability.


Assuntos
Células-Tronco Mesenquimais , Neuropatia Ciática , Animais , Medula Óssea , Endotelina-1 , Humanos , Camundongos , Nervo Isquiático
13.
Cell Biosci ; 11(1): 120, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210352

RESUMO

BACKGROUND: The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don't know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver. METHODS AND RESULTS: When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector. CONCLUSIONS: Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.

14.
J Clin Med ; 10(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34300190

RESUMO

BACKGROUND: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting. METHODS: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group (n = 935) and a non-LMB group (n = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. RESULTS: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, p < 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF. CONCLUSIONS: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.

15.
Circ J ; 85(11): 1944-1955, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34078776

RESUMO

BACKGROUND: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. CONCLUSIONS: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

16.
Medicine (Baltimore) ; 100(19): e25765, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106607

RESUMO

ABSTRACT: This study evaluated the 5-year clinical outcomes of the Genoss DES, the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.We previously conducted the first-in-patient prospective, multicenter, randomized trial with a 1:1 ratio of patients using the Genoss DES and Promus Element stents; the angiographic and clinical outcomes of the Genoss DES stent were comparable to those of the Promus Element stent. The primary endpoint was major adverse cardiac events (MACE), which was a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR) at 5 years.We enrolled 38 patients in the Genoss DES group and 39 in the Promus Element group. Thirty-eight patients (100%) from the Genoss DES group and 38 (97.4%) from the Promus Element group were followed up at 5 years. The rates of MACE (5.3% vs 12.8%, P = .431), death (5.3% vs 10.3%, P = .675), TLR (2.6% vs 2.6%, P = 1.000), and target vessel revascularization (TVR) (7.9% vs 2.6%, P = .358) at 5 years did not differ significantly between the groups. No TLR or target vessel revascularization was reported from years 1 to 5 after the index procedure, and no MI or stent thrombosis occurred in either group during 5 years.The biodegradable polymer Genoss DES and durable polymer Promus Element stents showed comparable low rates of MACE at the 5-year clinical follow-up.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Implantes Absorvíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polímeros , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , República da Coreia , Sirolimo/uso terapêutico , Resultado do Tratamento
17.
Stem Cell Res Ther ; 12(1): 346, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34116724

RESUMO

BACKGROUND: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. METHODS: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. RESULTS: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. CONCLUSIONS: These results indicate that shikimic acid is an effective agent for tissue regeneration.


Assuntos
Células-Tronco Multipotentes , Ácido Chiquímico , Diferenciação Celular , Células Cultivadas , Fibroblastos , Humanos , Pele
18.
Hypertens Res ; 44(9): 1099-1104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34145423

RESUMO

The objective of this work was to investigate the long-term safety and efficacy of renal denervation in Korean patients from the Global SYMPLICITY Registry (GSR). GSR Korea is a substudy of GSR with additional inclusion and exclusion criteria compared to GSR, including inclusion criteria of office systolic blood pressure ≥160 mmHg, or ≥150 mmHg for type 2 diabetes patients, while receiving 3 or more antihypertensive medications without changes for 2 weeks prior to enrollment. Renal denervation was performed using a Symplicity Flex catheter for ablation in the main renal arteries. Changes in office systolic blood pressure and adverse events were collected for up to 36 months of follow-up for 102 patients in GSR Korea. In addition, adverse events and reductions in office systolic blood pressure were analyzed for patients with and without type II diabetes mellitus. Renal denervation led to mean (± standard deviation) reductions in office systolic blood pressure at 12, 24, and 36 months in GSR Korea (-26.7 ± 18.5, -30.1 ± 21.6 mmHg, and -32.5 ± 18.8, respectively). The proportion of patients with a ≥10 mmHg office systolic blood pressure reduction from baseline was 86.3% at 12 months, 86.5% at 24 months, and 89.7% at 36 months. Adverse events at 3 years were rare. In addition, reductions in office systolic blood pressure were similar for patients with vs. without diabetes mellitus (p > 0.05 at all timepoints). Office systolic blood pressure was safely reduced at up to 36 months post-renal denervation in GSR Korea, and adverse events were rare. In addition, patients with and without diabetes had similar office systolic blood pressure reductions.

19.
Stem Cells Int ; 2021: 8873383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093711

RESUMO

Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4+ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.

20.
J Lipid Atheroscler ; 10(2): 210-222, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34095013

RESUMO

Objective: Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin. Methods: After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected. Results: Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; p<0.001; I2=94.7, respectively). Conclusion: As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...