Reduced primary patency rate in diabetic patients after percutaneous intervention results from more frequent presentation with limb-threatening ischemia

ObjectiveAlthough patients with diabetes are at increased risk of amputation from peripheral vascular disease, excellent limb-salvage rates have been achieved with aggressive surgical revascularization. It is less clear whether patients with diabetes will fare as well as nondiabetics after undergoing percutaneous lower extremity revascularization, a modality which is becoming increasingly utilized for this disease process. This study aimed to assess differential outcomes in between diabetics and nondiabetics in lower extremity percutaneous interventions.MethodsWe retrospectively studied 291 patients with respect to patient variables, complications, and outcomes for percutaneous interventions performed for peripheral occlusive disease between 2002 and 2005. Tibial vessel run-off was assessed by angiography. Patency (assessed arterial duplex) was expressed by Kaplan-Meier method and log-rank analysis. Mean follow-up was 11.6 months (range 1 to 56 months).ResultsA total of 385 interventions for peripheral occlusive disease with claudication (52.2%), rest pain (16.4%), or tissue loss (31.4%) were analyzed, including 336 primary interventions and 49 reinterventions (mean patient age 73.9 years, 50.8% male). Comorbidities included diabetes mellitus (57.2%), chronic renal insufficiency (18.4%), hemodialysis (3.8%), hypertension (81.9%), hypercholesterolemia (57%), coronary artery disease (58%), tobacco use (63.2%). Diabetics were significantly more likely to be female (55.3% vs 40.8%), and suffer from CRI (23.5% vs 12.0%), a history of myocardial infarction (36.5% vs 18.0%), and <three-vessel tibial outflow (83.5% vs 71.8%), compared with nondiabetics, although all other comorbidities and lesion characteristics were equivalent between these groups. Overall primary patency (± SE) at 6, 12, and 18 months was 85 ± 2%, 63 ± 3% and 56 ± 4%, respectively. Patients with diabetes suffered reduced primary patency at 1 year compared with nondiabetics. For nondiabetics, primary patency was 88 ± 2%, 71 ± 4%, and 58 ± 4% at 6, 12, and 18 months, while for diabetics it was 82 ± 2%, 53 ± 4%, and 49 ± 4%, respectively (P = .05). Overall secondary patency at 6, 12, and 18 months was 88 ± 2%, 76 ± 3%, and 69 ± 3%, and did not vary by diabetes status. One-year limb salvage rate was 88.3% for patients with limb-threatening ischemia, which was also similar between diabetics and nondiabetics. While univariate analysis revealed that female gender, <three-vessel tibial outflow, and a history of tobacco use were all predictive of reduced primary patency (P < .05), none of these factors significantly impacted secondary patency or limb-salvage rate. Furthermore, only limb-threatening ischemia remained a significant predictor of outcome on multivariate analysis, suggesting that the poorer primary patency in diabetics is related primarily to their propensity to present with limb-threatening disease compared with nondiabetics.ConclusionPatients with diabetes demonstrate reduced primary patency rates after percutaneous treatment of lower extremity occlusive disease, most likely due to their advanced stage of disease at presentation. However, despite a higher reintervention rate, diabetics and others with risk factors predictive of reduced primary patency can attain equivalent short-term secondary patency and limb-salvage rates. Therefore, these patient characteristics should not be considered contraindications to endovascular therapy

Computer simulation as a component of catheter-based training

IntroductionComputer simulation has been used in a variety of training programs, ranging from airline piloting to general surgery. In this study we evaluate the use of simulation to train novice and advanced interventionalists in catheter-based techniques.MethodsTwenty-one physicians underwent evaluation in a simulator training program that involved placement of a carotid stent. Five participants were highly experienced in catheter-based techniques (>300 percutaneous cases), including carotid angioplasty and stenting (CAS); the remaining 16 participants were interventional novices (<5 percutaneous cases). The Procedicus VIST simulator, composed of real-time vascular imaging simulation software and a tactile interface coupled to angiographic catheters and guide wires, was used. After didactic instruction regarding CAS and use of the simulator, each participant performed a simulated CAS procedure. The participant's performance was supervised and evaluated by an expert interventionalist on the basis of 50 specific procedural steps with a maximal score of 100. Specific techniques of guide wire and catheter manipulation were subjectively assessed on a scale of 0 to 5 points based on ability. After evaluation of the initial simulated CAS procedure, each participant received a minimum of 2 hours of individualized training by the expert interventionalist, with the VIST simulator. Each participant then performed a second simulated CAS procedure, which was graded with the same scale. After completion, participants assessed the training program and its utility via survey questionnaire.ResultsThe average simulated score for novice participants after the training program improved significantly from 17.8 ± 15.6 to 69.8 ± 9.8 (P < .01), time to complete simulation decreased from 44 ± 10 minutes to 30 ± 8 minutes (P < .01), and fluoroscopy time decreased from 31 ± 7 minutes to 23 ± 7 minutes (P < .01). No statistically significant difference in score, total time, or fluoroscopy time was noted for experienced interventionalists. Improvement was noted in guide wire and catheter manipulation skills in novices.. Analysis of survey data from experienced interventionalists indicated that the simulated clinical scenarios were realistic and that the simulator could be a valuable tool if clinical and tactile feedback were improved. Novices also thought the simulated training was a valuable experience, and desired further training time.ConclusionsAn endovascular training program using the Procedicus VIST haptic simulator resulted in significant improvement in trainee facility with catheter-based techniques in a simulated clinical setting. Novice participants derived the greatest benefit from simulator training in a mentored program, whereas experienced interventionalists did not seem to derive significant benefit

Categorizing and Defining Popular Psychological Terms Used Within the Youth Athlete Talent Development Literature: A Systematic Review

Inconsistencies in the use and definition of psychological terms within the talent development literature have been identified. To advance the scientific field, the creation of a shared language is recommended. This review aimed to systematically (i) identify terms used in empirical studies to describe psychological components purported to facilitate athletes' development; (ii) analyse definition and meanings of these terms; and (iii) group, label and define terms into meaning clusters. A systematic review using a narrative approach to synthesise information was conducted. A comprehensive literature search of SPORTDiscus, PsycINFO, PsycARTICLES, and ERIC was completed in May 2015. In total 21 empirical studies, published between 2002 and 2015, met the inclusion criteria and were included in the narrative synthesis. Thematic analysis was used to analyse the findings. Identified psychological terms were categorised as psychological skills or psychological characteristics. Psychological skills were defined as athletes’ ability to use learned psychological strategies (e.g., self-talk) to regulate and facilitate the enhancement of psychological characteristics. Psychological characteristics were defined as predispositions that impact upon athlete development (e.g., self-confidence). Despite being relatively enduring and consistent across a range of situations, psychological characteristics can be regulated and enhanced through the use of psychological skills

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo

Complexity of the Inoculum Determines the Rate of Reversion of SIV Gag CD8 T Cell Mutant Virus and Outcome of Infection

Escape mutant (EM) virus that evades CD8+ T cell recognition is frequently observed following infection with HIV-1 or SIV. This EM virus is often less replicatively “fit” compared to wild-type (WT) virus, as demonstrated by reversion to WT upon transmission of HIV to a naïve host and the association of EM virus with lower viral load in vivo in HIV-1 infection. The rate and timing of reversion is, however, highly variable. We quantified reversion to WT of a series of SIV and SHIV viruses containing minor amounts of WT virus in pigtail macaques using a sensitive PCR assay. Infection with mixes of EM and WT virus containing ≥10% WT virus results in immediate and rapid outgrowth of WT virus at SIV Gag CD8 T cell epitopes within 7 days of infection of pigtail macaques with SHIV or SIV. In contrast, infection with biologically passaged SHIVmn229 viruses with much smaller proportions of WT sequence, or a molecular clone of pure EM SIVmac239, demonstrated a delayed or slow pattern of reversion. WT virus was not detectable until ≥8 days after inoculation and took ≥8 weeks to become the dominant quasispecies. A delayed pattern of reversion was associated with significantly lower viral loads. The diversity of the infecting inoculum determines the timing of reversion to WT virus, which in turn predicts the outcome of infection. The delay in reversion of fitness-reducing CD8 T cell escape mutations in some scenarios suggests opportunities to reduce the pathogenicity of HIV during very early infection

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction &gt; 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD