2세대 약물용출스텐트 삽입후 자연경과와 심근경색환자에서의 사용성적에 관한 연구

학위논문(박사)--서울대학교 대학원 :의과대학 의학과,2020. 2. 김효수.Abstract Objectives We investigated the course of in-stent restenosis and evaluated the revascularization strategy in patients with ST-segment elevation myocardial infarction (STEMI) in a large scale registry. Background The progression of restenosis has not been fully evaluated in 2nd-generation drug eluting stents era. Moreover, the completeness of revascularization in STEMI patients with high risk factors is uncertain. Methods We investigated and analyzed the restenosis course of 944 stented lesions from 394 patients who had at least two serial follow-up angiograms, using quantitative coronary angiography analysis. A total of 1,311 STEMI patients with multivessel coronary artery disease were analyzed. Complete revascularization (CR) was defined by angiography and by a residual SYNTAX score <8. The primary study endpoints were patient oriented composite outcome (POCO) and cardiac death during 3-year follow-up. We also evaluated the effects of CR in patients with diabetes mellitus patients and those with reduced left ventricle (LV) function. Results The restenosis progression velocity of diameter stenosis was 12.1±21.0%/year and 3.7±10.1%/year during the first and second follow-up periods, respectively, which showed no significant difference (p>0.05) between contemporary stents. Overall, patients who underwent angiographic CR (579 patients, 44.2%) had significantly fewer 3-year clinical events than those of patients who underwent incomplete revascularization (IR). (POCO: 14.9% and 24.0%, p<0.001, cardiac death: 3.5% and 8.9%, p<0.001, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (adjusted HR 0.63, 95% CI 0.48-0.83) and cardiac death (adjusted hazard ratio [HR] 0.51, 95% CI 0.29-0.89). The results were corroborated using SS-based CR definition. When divided into subgroups according to the presence of diabetes, CR significantly reduced 3-year POCO (adjusted HR 0.52, 95% CI 0.35-0.76) only in the non-diabetes group. When the patients were divided into subgroups according to baseline left ventricular (LV) function, CR significantly reduced 3-year POCO (adjusted HR 0.58, 95% CI 0.43-0.82) only in the preserved LV function group. Conclusions The progression rate of in-stent restenosis differed at different time intervals. Contemporary stents had similar rates of restenosis progression. CR could improve clinical outcomes in STEMI patients with multivessel disease. However, the beneficial effect of CR neutralized in those with diabetes mellitus or reduced LV function.초록 연구목적 본 연구는 대규모 다기관 레지스트리를 통하여 ST 분절 상승 급성 심근경색환자에서 완전 재관류술과 비완전 재관류술의 3년 임상결과를 비교하고자 한다. 또한 스텐트내재협착의 진행률에 대해 조사해보려고 한다. 본 연구는 스텐트내재협착의 진행경과에 대해 조사하였다. 또한 대규모 다기관 레지스트리를 통하여 ST 분절 상승 급성 심근경색환자에서 관상동맥 스텐트 치료방식에 따른 3년 임상결과를 비교하고자 한다. 연구배경 2세대 약물용출스텐트의 재협착의 진행률에 대하여 완전히 평가되지 않았다. 위험인소를 동반한 ST 분절 상승 급성 심근경색환자들에서 완전 재관류술의 치료 효과는 확실하지 않다. 연구방법 스텐트 시술후 두 차례의 병원 방문으로 조영술을 시행하고 정량적 관상동맥조영술 분석을 진행한 394명 환자의 944개의 관상동맥 병변의 진행경과에 대해 조사 및 분석을 진행하였다. 또한 총 1311명의 ST 분절 상승 급성 심근경색 다혈관 질환 환자들에서 분석을 진행하였다. 완전 재관류술은 혈관조영술상의 판독과 잔여 SYNTAX 점수<8점, 두 가지 방법으로 정의를 하였다. 임상예후는 환자 연관 사건인 사망, 심근경색, 재시술(Patient oriented composite outcome)과 심장사를 주요 종결점으로 설정하였다. ST 분절 상승 급성 심근경색환자들에서 당뇨병과 좌심실기능저하의 동반여부에 따라 완전 재관류술의 효과를 평가하였다. 결과 재협착의 진행경과에 대한 분석결과를 보았을 때 스텐트 삽입후 재협착의 진행률은 9개월 전과 9개월후에 다르게 보여졌으며 각각 12.1±21.0%/년, 3.7±10.1%/년 이였다. 또한 현시대의 약물용출스텐트들간 재협착의 진행정도와 진행속도은 유의한 차이를 보이지 않았다(p>0.05). 완전 재관류술을 받은 환자는(579명, 44.2%) 비완전 재관류술을 받은 환자에 비해 3년 임상사건의 발생률이 유의하게 낮았다. (환자 연관 사건: 14.9% vs. 24.0%, p<0.001; 심장사: 3.5% vs. 8.9%, p<0.001). 다변량 분석에서도 완전 재관류술이 3년 환자 연관 사건과 심장사를 유의가게 줄였음을 보여 준다. [환자 연관 사건: 보정 위험비 0.63(0.48-0.83); 심장사: 보정 위험비 0.51(0.29-0.89)]. 또한 잔여 SYNTAX 점수에 근거하여 정의한 완전 재관류술의 평가에서도 완전 재관류술의 효과가 보여졌다. 당뇨병의 동반 여부에 따라 분석을 진행해 보았을 때, 완전 재관류술은 당뇨병을 동반하지 않은 환자그룹에서만 3년 환자 연관 사건을 유의하게 줄였다 [보정 위험비 0.52(0.35-0.76)]. 또한 좌심실기능저하의 동반 여부에 따라 분석을 진행해 보았을 때, 완전 재관류술은 좌심실 기능저하를 동반하지 않은 환자그룹에서만 3년 환자 연관 사건을 유의하게 줄였다 [보정 위험비 0.58(0.43-0.82)]. 결론 스텐트내재협착의 진행률은 초기와 후기에 다르게 진행 되었고 현시대의 약물용출스텐트들은 비슷한 재협착 진행률을 보였다. 완전 재관류술은ST 분절 상승 급성 심근경색 다혈관 질환 환자의 임상 결과를 개선 할 수 있다. 하지만 완전 재관류술은 당뇨병 혹은 좌심실기능저하를 동반한 환자에서는 효과를 보이지 않았다.General Introduction 1 Chapter 1. Progression of restenosis in stented coronary 3 Introductions 4 Methods 5 Results 10 Discussion 13 Conclusion 16 Chapter 2. Comparative analysis of coronary stent therapy in patients with myocardial infarction 18 Introductions 19 Methods 22 Results 27 Discussion 32 Conclusion 40 References 41 Tables 55 Figures 91 Abstract (in Korean) 106Docto

Promjena tlačne čvrstoće zida nakon korozije sulfatom uz visoku koncentraciju Ca2+

At the bedrock section of the auxiliary shaft of the Tong-ting coal mine, the sidewall has varying degradation degrees in different parts. The part on which water flowed is barely corroded, whereas the moist part near the pouring joints is seriously corroded. We first studied the mechanism of this phenomenon by chromatography, X-ray diffraction, and energy-dispersive X-ray spectroscopy. We then used simplified models built by particle flow code software (i.e., particle flow code in three dimensions, PFC3D) to analyse how increasing degradation depth affects compressive strength and failure patterns. The results were as follows. (1) Gypsum and calcite in corrosive water were supersaturated. The part on which water flowed was protected by the crystallized precipitation on the concrete. By contrast, the degradation of the part where water flowed through pouring joints was aggravated by internal crystallization and dissolution. (2) PFC3D numerical simulation indicated that decreases in vertical ultimate stress were strongly linearly correlated with degradation depth. As for the −355.5 m damaged part, reinforcement should be conducted before degradation depth reaches 250 mm. (3) No obvious signs were observed prior to the failure of the corroded sidewall. Therefore, the development of degradation depth should be monitored before degradation parts are reinforced.U pomoćnom oknu rudnika ugljena Tong-ting u pojasu temeljne stijene pojedini dijelovi zida pokazuju različite stupnjeve propadanja. Područja na kojima je tekla voda malo su korodirana, dok su vlažni dijelovi uz izljeve izrazito korodirani. Mehanizmi te pojave najprije su proučavani kromatografijom, rendgenskom difrakcijom i energijski disperzivnom rendgenskom spektroskopijom. Veza između dubine korozije i tlačne čvrstoće te obrasca sloma analizirana je pojednostavljenim modelom utemeljenim na kôdu toka čestica (kôd toka čestica u tri dimenzije, PFC3D). (1) Voda je prezasićena s obzirom na gips i kalcit. Dijelovi preko kojih je voda tekla zaštićeni su precipitatom na betonu. Nasuprot tome, propadanje je pojačano kristalizacijom i otapanjem u nutrini izljeva. (2) Numerička simulacija modelom PFC3D pokazuje linearnu vezu između smanjenja vertikalnog maksimalnog naprezanja i dubine degradacije. Oštećeni dio na −355,5 m trebat će pojačati prije nego korozija dopre do 250 mm dubine. (3) Nisu bili uočeni jasni pokazatelji propadanja prije sloma korodiranog zida. Stoga treba pratiti napredovanje propadanja prije nego uništeni dijelovi budu ojačani

Thermal resistance effect on anomalous diffusion of molecules under confinement

Diffusion is generally faster at higher temperatures. Here, a counterintuitive behavior is observed in that the movement of long-chain molecules slows as the temperature increases under confinement. This report confirms that this anomalous diffusion is caused by the “thermal resistance effect,” in which the diffusion resistance of linear-chain molecules is equivalent to that with branched-chain configurations at high temperature. It then restrains the molecular transportation in the nanoscale channels, as further confirmed by zero length column experiments. This work enriches our understanding of the anomalous diffusion family and provides fundamental insights into the mechanism inside confined systems.This work is supported by the National NaturalScience Foundation of China (22032005, 21902180, 21802164, 21991092,21991090, 22002174 and 91645112), and the Natural Science Foundation ofHubei Province of China (2018CFA009), the Key Research Program of FrontierSciences, Chinese Academy of Sciences (QYZDB-SSW-SLH026), and SinopecCorp. (417012-4). We are grateful to the Shenzhen Cloud Computing Centerfor their support in computing facilities.Peer reviewe

Genome and transcriptome analysis of Enterococcus faecium from intestinal colonization and Enterococcus faecium from urinary tract infection

IntroductionEnterococcus faecium is a common pathogen responsible for urinary tract infections (UTIs) and often establishes extensive colonization within the intestinal tract. Our aim was to assess the genomic and transcriptomic differences between colonized E. faecium without UTI (only-colonization) and colonized E. faecium causing UTI (endogenous infections).MethodWe investigated the correlation between fecal isolates from the same patient and UTI-causing isolates using PFGE and WGS, and classified fecal isolates into two groups: those that solely colonized and those associated with endogenous urinary tract infections. We characterized the genomes of colonization-only and endogenously infected isolates by Scoary GWAS, and the transcriptomes of the isolates at 3 h urine exposure to assess pathogen-related changes.ResultBased on PFGE and WGS, eight isolates of endogenously infected E. faecium and nine isolates of only-colonized E. faecium were characterized and carbon and nitrogen regulated metabolisms such as genes encoding the phosphotransferase (PTS) system were enriched in endogenously infected E. faecium. Transcriptome analysis revealed significant differences in gene expression in the PTS system, lysine synthesis, galactose metabolism and citrate import between endogenously infected and only-colonized E. faecium isolates, highlighting the important role of certain carbon regulatory genes in the colonization and survival of endogenously infected E. faecium.ConclusionIn only-colonized and endogenously infected isolates, we observed differential expression patterns of genes related to carbon metabolism and amino acids, suggesting that metabolic diversity is a strategy for isolates leading to endogenous infection

Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry

Background: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated. Methods: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097–1140 days), and the primary endpoint was cardiac death at 3 years. Results: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and STEMI in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53–0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65–1.44, p = 0.884). Conclusions: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality

Multitasking scheduling problems with a rate-modifying activity

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Thin film hydride generation: determination of ultra-trace copper by flow injection in situ hydride trapping graphite furnace AAS

A novel system which significantly enhances copper hydride generation efficiency was used for the determination of trace copper by coupling a flow injection system to a graphite furnace for in situ collection of the analyte and subsequent AAS detection. A single device integrated the functions of hydride generator and gas liquid separator. Solutions of the sample containing 0.0005% (m/v) phenanthroline and 1% formic acid were merged with tetrahydroborate reductant to yield a thin film wetting a reaction surface from which product vapor was efficiently liberated and transported to the heated furnace. Optimum operating conditions provided for a generation/transport/collection efficiency of 8\u201312%. Interferences from common transition and noble metals were effectively eliminated. A limit of detection of 100 pg ml 121 was obtained based on processing a 1 ml sample volume. A precision of better than 4% (RSD) at 1 ng ml 121 was typical. The methodology was successfully applied to the determination of Cu in several NRCC natural water and biological tissue Certified Reference MaterialsPeer reviewed: YesNRC publication: Ye

Algorithms for the joint multitasking scheduling and common due date assignment problem

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Optimal Semi-Online Algorithm for Scheduling on Two Parallel Batch Processing Machines

International audienceBatch processing machine scheduling in uncertain environment attracts more and more attention in the last decade. This paper deals with semi-online scheduling on two parallel batch processing machines with non-decreasing processing time of job. Jobs arrive over time in the online paradigm, and the processing time of any batch is equal to the length of the last arrival job in the batch. We study the unbounded model where each processing batch may contain an unlimited number of jobs, and the objective is to minimize the makespan. Given any job (Formula presented.) together with its following job (Formula presented.), it is assumed that their processing times satisfy (Formula presented.) where α ≥ 1 is a constant. That is, jobs arrive in a non-decreasing order of processing times. We mainly propose an optimal ϕ-competitive online algorithm where ϕ ≥ 1 is a solution of equation ϕ3 + (α-1)ϕ2 + (α2 - α - 1)ϕ - α2 = 0