Deciphering IgM interference in IgG anti-HLA antibody detection with flow beads assays

In flow beads assays, the interference of IgM for IgG anti-HLA antibodies detection is not precisely understood. Using the screening flow beads assay for class I HLA antibodies, we analyzed the binding of two IgG mAbs, the anti-class I HLA W6/32 and an anti-beta-2-microglobulin, in the presence of an anti-beta-2-microglobulin IgM mAb. In neat serum, the IgM mAb impaired the detection of both IgG. In EDTA-treated serum, the interference was stronger for the anti-beta-2-microglobulin IgG than for W6/32, in agreement with the finding in surface plasmon resonance that this IgM competed with the anti-beta-2-microglobulin IgG but not with W6/32. The IgM interference was higher in neat than in EDTA-treated serum for both IgG mAbs. The IgM interference was also analyzed with class II single antigen flow beads and sera from two kidney recipients containing IgG and IgM donor specific antibodies. Anti-HLA IgG detection was partially corrected by EDTA, and restored by IgM inactivation with DTT, confirming the results observed with the mAbs. Therefore, three mechanisms can explain the IgM interference for IgG anti-HLA antibodies in flow beads assays: direct competition for antigen, steric hindrance and complement activation.     

Very Long-term Outcomes and Predictors of Percutaneous Coronary Intervention with Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Patients with Unprotected Left Main Coronary Artery Disease

Background:

There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events.

Methods:

All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups.

Results:

Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3–8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group.

Conclusions:

During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.     

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome: five-year results from a large cohort study

BACKGROUND: To investigate the most appropriate dual antiplatelet therapy (DAPT) duration for patients with acute coronary syndrome (ACS) after drug-eluting stent (DES) implantation in the largest cardiovascular center of China.     

Novel co-axial prilling technique for the development of core–shell particles as delayed drug delivery systems

In this study, biocompatible double layered beads consisting of pectin core and alginate shell were prepared through a single step manufacturing process based on prilling apparatus equipped with co-axial nozzles. The core was loaded with piroxicam (PRX) as model non-steroidal anti-inflammatory drug (NSAID). Morphology, size distribution and shape of the double layered beads varied depending on the operative conditions and polymer concentrations. Co-axial nozzles size, applied vibration frequency, gelling conditions and, mainly, polymers mass ratio were identified as critical variables. Particularly, the relative viscosity of polymeric feed solutions inside the nozzle was the key parameter to obtain homogeneous and well-formed coated particles. The produced beads were investigated for the release kinetic in different media. Once PRX was encapsulated within the pectin core, a controlled release pattern was observed. Particularly, beads produced with 4:1 core/shell ratio (F4) released less than 30% of PRX in simulated gastric fluid (SGF) while total liberation of the drug was achieved during the next 3 h in simulated intestinal fluid (SIF). More interesting, F4 tested in SIF was able to release drug in a delayed and sustained manner at established time points (2h_8.2%, 3h_32.2%, 4h_70.1% and 5h_about 100%). Based on the above results, co-axial prilling approach is expected to provide success in manufacturing systems with delayed drug release profiles. Such systems may be potentially useful in targeting diseases which are affected by the circadian rhythm, such as chronic inflammation.     

Clinical outcomes of patients treated with Nobori biolimus-eluting stent: Meta-analysis of randomized trials

Backgrounds

The Nobori is a new-generation, biodegradable-polymer coated, biolimus-eluting stent (BES) that has recently been investigated in several randomized trials with inconsistent results. The aim of this study was to assess the efficacy and safety of Nobori BES versus other drug-eluting stents (DES) in patients treated with percutaneous coronary intervention (PCI).

Methods

We undertook a meta-analysis of randomized trials investigating Nobori BES versus other DES. Primary efficacy and safety outcomes were target lesion revascularization (TLR) and definite/probable stent thrombosis (ST), respectively. Secondary outcomes were the composite of cardiac death/myocardial infarction (MI)/target vessel revascularization (TVR), MI and death.

Results

A total of 9114 PCI-patients randomly received Nobori BES (n = 5080) or other DES (n = 4034). This latter group comprised patients receiving everolimus- (n = 2533), sirolimus- (n = 1376) or paclitaxel-eluting stents (n = 125). Median follow-up was 11 months [interquartile range 9–12]. The Nobori BES versus other DES showed comparable risk of TLR (odds ratio [95% confidence interval] = 0.91 [0.57–1.46], p = 0.71). There was significant heterogeneity across trials due to significant lower TLR risk with Nobori BES versus paclitaxel-eluting stent (0.32 [0.10–0.98], p = 0.046; p for interaction = 0.009). Nobori BES versus other DES showed comparable risk of definite/probable ST (1.40 [0.66–2.97], p = 0.39), cardiac death/MI/TVR (1.05 [0.88–1.25], p = 0.59), MI (1.13 [0.87–1.48], p = 0.37) and death (1.09 [0.81–1.48], p = 0.56).

Conclusions

Nobori BES has comparable efficacy with other limus-eluting stents at 1-year follow-up. There is no difference in terms of safety profile between these stent platforms.     

Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting stents in diabetics with multi-vessel disease: An updated systematic review and meta-analysis

Background

Currently, the appropriateness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is uncertain due to limited evidence from few randomised controlled trials (RCTs). We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD patients using an evidence-based approach.

Methods

A systematic review and meta-analyses were conducted to compare the risk of all-cause mortality, myocardial infarction (MI), repeat revascularisation, cerebrovascular events (CVE), and major adverse cardiac or cerebrovascular events (MACCE).

Results

A total of 1,837 and 3,052 DM-MVD patients were pooled from four RCTs (FREEDOM, SYNTAX, VA CARDS, and CARDia) and five non-randomised studies. At mean follow-up of 3 years, CABG compared with PCI-DES was associated with a lower risk of all-cause mortality and MI in RCTs. By contrast, no significant differences were observed in the mean 3.5-year risk of all-cause mortality and MI in non-randomised trials. However, the risk of repeat revascularisations following PCI-DES compared with CABG was 2.3 (95% CI = 1.8–2.8) and 3.0 (2.3–4.2)-folds higher in RCTs and non-randomised trials, respectively. Accordingly, the risk of MACCE at 3 years following CABG compared with PCI-DES was lower in both RCTs and non-randomised trials [0.65 (: 0.55–0.77); and 0.77 (0.60–0.98), respectively].

Conclusions

Based on our pooled results, we recommend CABG compared with PCI-DES for patients with DM-MVD. Although non-randomised trials suggest no additional survival-, MI-, and CVE- benefit from CABG over PCI-DES, these results should be interpreted with care.     

Stent thrombosis is not increased following percutaneous coronary intervention in patients with non-insulin dependent diabetes mellitus taking metformin

Objective

Recent studies have suggested that metformin may inhibit endothelialization following limus-eluting stent (LES) placement and may increase the risk of stent thrombosis. Therefore, we assessed the impact of metformin on stent thrombosis and major adverse cardiovascular events (MACE) in non-insulin-dependent diabetes mellitus (NIDDM) patients who receive drug-eluting stents (DES).

Methods

We assessed the impact of metformin and stent type on stent thrombosis, MACE, and death in NIDDM patients following DES placement. Of the 1201 patients included, 74.8% received LES, 25.2% received paclitaxel-eluting stents (PES), and 55% were taking metformin.

Results

There was no difference in stent thrombosis, regardless of stent type or metformin use. While Kaplan–Meier curves demonstrated reduced MACE (p = 0.007) and death (p = 0.006) with metformin use, multivariate analysis demonstrated that stent type and metformin use were not associated with outcome.

Conclusion

In NIDDM patients, metformin use or stent type following DES placement did not increase stent thrombosis and MACE rates.     

进口与国产药物洗脱支架治疗急性ST段抬高心肌梗死的预后分析

目的 进口和国产药物洗脱支架（DES）治疗急性ST段抬高心肌梗死（STEMI）的住院期间与远期预后比较.方法 连续入选2009年1月至2010年8月的197例确诊急性STEMI并行冠状动脉介入治疗的患者,按照支架的类型分为国产DES组和进口DES组,比较两组住院期间和长期心脑血管事件发生率.结果 国产DES组共113例（57.4％）,进口DES组84例（42.6％）,两组住院期间全因死亡率（2.7％比4.8％,P=0.515）、严重心力衰竭发生率（2.7％比0,P=0.053）、恶性心律失常发生率（10.6％比3.6％,P=0.098）差异均无统计学意义;两组患者随访中位数41个月,随访期内两组的无事件生存率分别为91.5％和90.9％ （P=0.885）.多因素分析显示,高龄（HR=1.872,95％ CI：1.008～2.118,P=0.023）、高血压史（HR=6.018,95％ CI：1.307～21.716,P=0.021）、脑血管病史（HR=4.995,95％ CI：1.536～16.242,P=0.008）、心功能Killip分级（HR=3.947,95％ CI：1.809～8.612,P=0.001）、高尿酸血症（HR=1.006,95％ CI：1.003～1.010,P＜0.001）是患者远期发生全因死亡、非致死性心肌梗死、再次血运重建、严重心力衰竭、脑血管病的独立危险因素.结论 急性STEMI患者,应用国产与进口DES住院期间及远期预后差异无统计学意义.