Management of Guidewire Entrapment and Fracture During Percutaneous Coronary Intervention: When All Bailout Techniques Fail!

A 55-year-old man presented with chest pain and was diagnosed with non-ST-segment elevation myocardial infarction. Coronary angiography revealed a 95% eccentric lesion in the mid-right coronary artery. After 3 intracoronary stents were placed, the guidewire became entrapped in 1 of the stents; multiple attempts at retrieval were unsuccessful. Ultimately, the guidewire fractured, and a coronary artery bypass graft surgery was performed to remove the guidewire fragments. This report reviews the procedural steps for wire retrieval that are critical for operators to avoid coronary artery bypass surgery.

Clinical role of the Duke Activity Status Index in the selection of the optimal type of stress myocardial perfusion imaging study in patients with known or suspected ischemic heart disease.

BACKGROUND: Exercise treadmill stress myocardial perfusion imaging (MPI) with single photon emission computed tomography is commonly used to evaluate the extent and severity of inducible ischemia as well as to risk stratify patients with suspected and known coronary artery disease (CAD). Failure to reach adequate stress, defined as not attaining age-appropriate metabolic equivalents (METs), can underestimate the extent and severity of ischemic heart disease, resulting in false negative results. This study evaluates the efficacy of the Duke Activity Status Index (DASI), a simple self-administered 12-item questionnaire, as a predictor of METs achieved by treadmill stress testing. METHODS: The DASI was prospectively administered to 200 randomly selected men and women referred to the nuclear cardiology laboratory at New York University Langone Medical Center for stress MPI. Each patient was asked to complete the 12-item DASI questionnaire independently. 136 patients underwent treadmill exercise with MPI and 64 had pharmacologic stress with MPI. The association between exercise capacity in METs as estimated by the DASI questionnaire and performance on the Bruce treadmill protocol in METS was compared using chi-square statistics. RESULTS: Over 70% of those patients whose DASI score predicted the ability to perform <10 METs were unable to exercise beyond stage 2 of the Bruce protocol (7 METs). For those whose DASI score predicted ability to perform >12.5 METs, over 80% of patients reached >stage 2 of the Bruce protocol with 40% reaching beyond stage 3 (10 METs). When patient age was incorporated into the calculation, a more linear relationship was observed between predicted and obtained METs. CONCLUSION: The DASI is a simple self-administered questionnaire which is a useful pretest tool to determine a patient's ability to achieve appropriate METs. In the nuclear cardiology laboratory, the DASI has the potential to guide selection of exercise treadmill vs pharmacologic stress and ultimately improve laboratory efficiency.

T-705 induces lethal mutagenesis in Ebola and Marburg populations in macaques.

Nucleoside analogues (NA) disrupt RNA viral RNA-dependent RNA polymerase (RdRP) function and fidelity for multiple viral families. The mechanism of action (MOA) of T-705 has been attributed alternatively or concurrently to chain termination and lethal mutagenesis depending on the viral species during in vitro studies. In this study, we evaluated the effect of T-705 on the viral population in non-human primates (NHPs) after challenge with Ebola virus (EBOV) or Marburg virus (MARV) to identify the predominant in vivo MOA. We used common virological assays in conjunction with deep sequencing to characterize T-705 effects. T-705 exhibited antiviral activity that was associated with a reduction in specific infectivity and an accumulation of low frequency nucleotide variants in plasma samples collected day 7 post infection. Stranded analysis of deep sequencing data to identify chain termination demonstrated no change in the transcriptional gradient in negative stranded viral reads and minimal changes in positive stranded viral reads in T-705 treated animals, questioning as a MOA in vivo. These findings indicate that lethal mutagenesis is a MOA of T-705 that may serve as an indication of therapeutic activity of NAs for evaluation in clinical settings. This study expands our understanding of MOAs of these compounds for the Filovirus family and provides further evidence that lethal mutagenesis could be a preponderant MOA for this class of therapeutic compounds.

Error baseline rates of five sample preparation methods used to characterize RNA virus populations.

Individual RNA viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. Understanding the variability of RNA virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. Reverse transcription of virus genome populations followed by next-generation sequencing is the only available method to characterize variation for RNA viruses. However, both steps may lead to the introduction of artificial mutations, thereby skewing the data. To better understand how such errors are introduced during sample preparation, we determined and compared error baseline rates of five different sample preparation methods by analyzing in vitro transcribed Ebola virus RNA from an artificial plasmid-based system. These methods included: shotgun sequencing from plasmid DNA or in vitro transcribed RNA as a basic "no amplification" method, amplicon sequencing from the plasmid DNA or in vitro transcribed RNA as a "targeted" amplification method, sequence-independent single-primer amplification (SISPA) as a "random" amplification method, rolling circle reverse transcription sequencing (CirSeq) as an advanced "no amplification" method, and Illumina TruSeq RNA Access as a "targeted" enrichment method. The measured error frequencies indicate that RNA Access offers the best tradeoff between sensitivity and sample preparation error (1.4-5) of all compared methods.