No abstract

Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(∗)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor.

Periprocedural outcome of the single-branched ISG was acceptable, and long-term safety and efficacy were demonstrated. However, the procedural complications of the multibranched ISG leave room for improvement.

Long-term safety and efficacy of drug-eluting stents remains controversial. The CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored multi-center registry enrolling consecutive patients undergoing first coronary revascularization in 26 centers in Japan. We compared 3-year outcome between patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare-metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was associated with significantly lower adjusted risk for all-cause death [hazard ratio (HR) [95% confidence interval (CI)] 0.72 (0.59-0.87), P = 0.0007], which was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48-0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63-1.07), P = 0.15], myocardial infarction [HR (95% CI) 0.73 (0.51-1.03), P = 0.07] and definite stent thrombosis [HR (95% CI) 0.62 (0.35-1.09), P = 0.1] was not different between the two groups. Despite longer duration of thienopyridine administration, SES-use was associated with significantly lower risk for bleeding [HR (95% CI) 0.75 (0.6-0.95), P = 0.02] and similar risk for stroke [HR (95% CI) 1.0 (0.75-1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was markedly lower in the SES group [HR (95% CI) 0.42 (0.36-0.48), P < 0.0001]. The direction and magnitude of the effect of SES relative to BMS in patients presenting acute myocardial infarction (AMI) were similar to those in patients presenting otherwise. In conclusion, SES-use as compared with BMS-use was associated with marked reduction of TLR without any increases in death, myocardial infarction, stent thrombosis, stroke and bleeding in real world clinical practice regardless of clinical presentation including AMI.

The aim of this study is to estimate the increase of bone-inductive potency by human demineralized dentin matrix (DDM) with recombinant human bone morphogenetic protein-2 (BMP-2). Human teeth were crushed, completely demineralized in 0.6M HCl, and freeze-dried. The tooth-derived material is called DDM. The shape of DDM was a particle type and its size varied from 0.4 to 0.8 mm. The BMP-2 dose-dependent study in the rat subcutaneous tissues demonstrated that the volume of induced bone and marrow increased at a dose-dependent manner. The time-course study of bone induction by the BMP-2 (5.0 μg)/DDM (70 mg) was estimated histologically and biochemically. Histological findings showed that the BMP-2/DDM increased bone and marrow sequentially between the DDM particles. Calcium content in the BMP-2/DDM-induced tissue was compatible to the histological findings. ALP activity in the BMP-2/DDM showed a maximal value at 1 week and gradually decreased. The morphometric analysis demonstrated that the BMP-2/DDM showed 66.9%, 79.0% in the volume of bone and marrow, and 32.4%, 21.0% in that of DDM at 8, 32 weeks, respectively. We confirmed that BMP-2 significantly accelerated bone formation in the acid-insoluble human-dentin carriers. These results indicate that human DDM should be an effective carrier for delivering BMP-2 and superior scaffold for bone-forming cells.

Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows estimation of the wound healing rate.

After propensity matching analysis for CLI patients other than those with both diabetes and wound infection, the wound healing rate was higher after direct revascularization than after indirect revascularization, whereas MALE and AFS were not significantly different.

n arterial thrombus formation, the interaction of adenosine diphosphate (ADP) with its receptor P2Y12 plays an important role in platelet activation and its maintenance. [1][2][3][4] Dual antiplatelet therapy with aspirin and thienopyridine derivative is the standard therapy for the prevention of stent thrombosis in patients after percutaneous coronary intervention (PCI). [5][6][7][8] Ticlopidine, a 1st-generation P2Y12 ADP receptor antagonist, has been reported to have a relative high rate of side-effects. 9 Clopidogrel, a 2nd-generation P2Y12 ADP receptor antagonist, has been demonstrated to reduce the risk of cardiovascular events in patients with prior vascular diseases, 10,11 and is widely used for secondary prevention in patients with coronary artery disease. However, it is well known that clopidogrel exerts little antiplatelet effect in a certain proportion of patients, a phenomenon termed "clopidogrel resistance". 12-15 Importantly, cardiovascular risk is elevated after coronary stent implantation in patients with clopidogrel resistance. 16 Clopidogrel is a prodrug that requires two-step biotransformation processes mediated mainly by 2 cytochrome p450 enzymes (CYP), CYP2C19 and CYP3A4. 17,18 Two major single nucleotide polymorphisms (SNPs) of CYP2C19 are known to make the enzyme activity non-functional. 19,20 One is CYP2C19*2, which is the mutation of guanine to adenine at position 681 in exon 5, causing a splicing defect, 19 and the other is CYP2C19*3, which is the mutation of guanine to adenine at position 636 in exon 4, forming a stop codon. 20 The frequency of the CYP2C19*2 or *3 mutation varies among races. The frequency of CYP2C19*2 in Asians is higher (30%) than in Western people (~15%), whereas the CYP2C19*3 allele has been reported as frequent in Asians (~5%) and rare in Caucasians (0.04%). 21 Results of a recent study of healthy volunteer subjects showed that CYP2C19 polymorphisms are associated with a weaker antiplatelet response to clopidogrel. 22 Furthermore, the plasma concentration of the active metabolite of clopidogrel is affected by CYP2C19 genotype. 23 However, to our knowledge no study has evaluated the effect of CYP2C19 polymorphisms on the antiplatelet effect of clopidogrel in actual clinical patients with cardiovascular risks on aspirin therapy. The SNP of CYP3A4 (IVS10 +12G>A) has been reported to enhance the antiplatelet effect of clopidogrel, 24 and the SNP of P2Y12 (T744C) has been reported to reduce the antiplatelet effect of clopidogrel when it coexists with CYP2C19 SNPs. 25 We recently systematically evaluated the antiplatelet effect of clopidogrel during low-dose aspirin therapy in 30 Japanese patients scheduled for PCI, and reported a wide inter-individual variation in the antiplatelet effect of clopidogrel, with 4 cases (14%) being classified as non-responders. 26 Comparison of our data with results from a similar study performed in the US 27 also showed that the effectiveness of Background: The P2Y12 adenosine diphosphate (ADP) receptor blocker, clopidogrel, an essential...