Clinical,angiographic and procedural characteristics of longitudinal stent deformation

Recently, longitudinal stent deformation (LSD) has been reported increasingly. Even though the reported cases included almost all stent designs, most cases were seen in the Element? stent design (Boston Scientific, Natick, MA, USA). It is considered that stent design, lesion and procedural characteristics play a role in the etiology of LSD. Yet, the effect of LSD on long-term clinical outcomes has not been studied well. Element stents implanted between January 2013 and April 2015 in our hospital were examined retrospectively. Patients were grouped into two according to the presence of LSD, and their clinical, lesion and procedural characteristics were studied. Twenty-four LSD’s were detected in 1812 Element stents deployed in 1314 patients (1.83?% of PCI cases and 1.32?% of all Element stents). LMCA lesions (16.7?% vs 1.6?%, p?<?0.001), complex lesions (75?% vs 35.1?%, p?<?0.001), bifurcation lesions (37.5?% vs 18.3?%, p?=?0.017), ostial lesions (33.3?% vs 12.8?%, p?=?0.003), using of extra-support guiding catheter (54.2?% vs 22.3?%, p?<?0.001) and extra-support guidewire (37.5?% vs 16.2?%, p?=?0.005) were found to be more frequent in cases with LSD than in cases without it. In addition, the number of stents, stent inflation pressure and the use of post-dilatation were significantly different between the two groups. Two patients had an adverse event during the follow-up period. LSD is a rarely encountered complication, and is more common in complex lesions such as ostial, bifurcation and LMCA lesions. The use of extra-support guiding catheter, extra-support guidewires and low stent inflation pressure increases the occurrence of LSD. Nevertheless, with increased awareness of LSD and proper treatment, unwanted long-term outcomes can be successfully prevented.     

Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area

Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.     

Predictors and clinical significance of angiographically detected distal embolization after primary percutaneous coronary interventions

OBJECTIVES: The aim of this study was to investigate clinical, angiographic and procedural predictors of distal embolization (DE) on angiography after primary percutaneous coronary intervention (PCI). The impact of DE on outcome in the first 30 days was also assessed. METHODS: Between January 2004 and April 2006, primary PCI was performed in 212 consecutive patients with acute myocardial infarction (AMI) of < or = 12-h duration. RESULTS: Distal embolization was present in 27 patients (12.7%) and more often observed in female sex (27.5 vs. 10.4%, P=0.01), in patients with right coronary artery involvement (52 vs. 28%, P=0.02), prerevascularization thrombolysis in myocardial infarction flow < or = 1 (89 vs. 69%, P=0.03), in the presence of high thrombus burden (92.6 vs. 39.5%, P=0.0009), and a long target lesion in the infarct-related artery (>14.5 mm, 74 vs. 29%, P<0.0001). By multiple stepwise logistic regression analysis, only the presence of high thrombus burden before the PCI procedure [odds ratio (OR)=5.2, 95% confidence interval (CI)=1.09-24.97, P=0.03)] and target lesion length (>14.5 mm, OR=3.9, 95% CI=1.45-10.60, P=0.007) were found independent predictors of DE. Patients with DE had an increased risk of target vessel revascularization (26 vs. 5%, P=0.001) and short-term mortality (29.6 vs. 7.5%, P=0.002) when compared with patients without angiographic signs of embolization. CONCLUSIONS: In patients who undergo primary PCI, high thrombus burden on angiography before PCI and/or a long target lesion in the infarct-related artery increase the risk of DE and subsequent short-term mortality.     

Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus

One way to dissect the antibody response to an invading microorganism is to clone the antibody repertoire from immune donors and subsequently characterize the specific antibodies. Recently, methodological advances have allowed investigations of neutralizing antibodies against hepatitis C virus (HCV) in vitro. We have investigated three human mAbs, previously isolated from an individual infected with HCV of genotype 2b, that are known to cross-react in a binding assay to the envelope E2 protein of genotypes 1a and 1b. We now report that two of them have a neutralizing activity with a breadth not previously observed. Indeed, mAbs 1:7 and A8 recognized E2 from all of the six major genotypes, and they neutralized retroviral pseudoparticles [HCV pseudoparticles (HCVpp)] carrying genetically equally diverse HCV envelope glycoproteins. Importantly, these antibodies were also able to neutralize the cell culture infectious HCV clone JFH-1 in vitro, with IC(50) values of 60 ng/ml and 560 ng/ml, respectively. The conformational epitopes of these two broadly reactive antibodies were overlapping yet distinct and involved amino acid residues in the 523-535 region of E2, known to be important for the E2-CD81 interaction. The third antibody clone, representing a dominant population in the initial screen for these antibodies, was less broadly reactive and was unable to neutralize the genotype 2a infectious clone JFH-1. Our results confirm at the clonal level that broadly neutralizing human anti-HCV antibodies can be elicited and that the region amino acids 523-535 of the HCV envelope glycoprotein E2 carries neutralizing epitopes conserved across all genotypes.     

FTO variants are associated with obesity in the Chinese and Malay populations in Singapore

OBJECTIVE— Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations.RESEARCH DESIGN AND METHODS— We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES).RESULTS— All nine SNPs exhibited strong linkage disequilibrium (r² = 0.6–0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m² (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m² (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m² (P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17–1.22; P ≤ 0.026).CONCLUSIONS— FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.A recent genome-wide association study for type 2 diabetes using a U.K.-based population revealed a novel locus associated with BMI: the fat mass–and obesity-related gene (FTO) on chromosome 16 (1). The representative single-nucleotide polymorphism (SNP), rs9939609, was confirmed to be associated with elevated BMI after replication in more than 38,000 study participants of European ancestry. Further replication of this association has been observed in several populations of distinctly European ancestry (2–6). However, this association is inconsistent in populations of non-European ancestry. A study in Japanese showed an association between variants at this locus and obesity (7) that was not observed in African Americans (6) or Han Chinese (8). The aims of this study were 1) to determine the associations between previously identified obesity-associated SNPs at the FTO locus with obesity and type 2 diabetes in Chinese, Malays, and Asian-Indians and 2) to examine whether any associations were modulated by exercise.     

Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn’s disease

Background The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. Aims To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. Patients and methods Three hundred eighty-eight German IBD patients [244 with Crohn’s disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype–phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. Results Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (χ² = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (χ² = 16.054, df = 8, p = 0.034 for age at diagnosis ≥25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 – 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (χ² = 16.101, df = 6, p = 0.017 for age at diagnosis ≥25). No association of MDR1 genotypes with disease subgroups in CD was observed. Conclusions While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.     

Lung vitamin E transport processes are affected by both age and environmental oxidants in mice

Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O(3)) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m(3) 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p<0.05) and 15% lower (p<0.05) in plasma and lung tissue, respectively, in aged versus young mice, acute environmental exposure to O(3) or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O(3) or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O(3) and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types.