Faculty Bibliography

Introduction: Thrombocytopenia is a common laboratory abnormality among patients presenting with acute myocardial infarction (AMI). We sought to evaluate associations between thrombocytopenia, in-hospital management and cardiovascular outcomes in patients hospitalized for AMI in the United States.
Method(s): Patients hospitalized from 2004 to 2014 with a primary diagnosis of AMI were identified from the National Inpatient Sample (NIS). Thrombocytopenia was identified based on ICD-9 codes. Multivariable logistic regression models were used to estimate odds of in-hospital adverse events stratified by thrombocytopenia and adjusted for demographics, cardiovascular risk factors, comorbidities, and treatment.
Result(s): A total of 6,717,769 patients were hospitalized with a primary diagnosis of AMI and thrombocytopenia was reported in 219,351 (3.3%). Patients with thrombocytopenia were older, more likely to have medical comorbidities, were more likely to undergo coronary artery bypass grafting [CABG] (28.8% vs. 8.2%, p<0.001), and were less likely to receive a drug eluting stent [DES] (15.5% vs. 29.5%, p<0.001). After multivariable adjustment, thrombocytopenia remained an independent predictor of in-hospital mortality, ischemic stroke, cardiogenic shock, cardiac arrest and bleeding complications (Table).
Conclusion(s): This is the largest analysis of AMI outcomes for patients with and without thrombocytopenia. AMI patients with thrombocytopenia have a significantly greater risk of adverse outcomes, are more likely to undergo CABG and less likely receive a DES during hospitalization compared to other AMI patients. Thrombocytopenia may identify AMI patients at high risk for in-hospital morbidity and mortality. Future investigations to mitigate the poor prognosis of patients with AMI and thrombocytopenia are warranted

Venous thromboembolism (VTE), comprised of deep vein thrombosis and pulmonary embolism, is a common health problem both in the United States and worldwide, with significant associated morbidity and mortality. Despite multiple known genetic and situational risk factors, an estimated 30% of all events remain classified as idiopathic, demonstrating a significant knowledge gap in the pathophysiology VTE. While platelets are well established as an essential contributor to thrombus formation and there has been recent interest in the role of neutrophil extracellular traps, specific cell types and pathways involved in the pathogenesis of VTE remain uncertain. In this study, our primary aims were to define a unique transcriptional signature for VTE and to identify the types of cells and specific pathways involved in development of VTE. Whole blood was collected in PAX gene tubes and RNA sequencing for coding mRNA was performed in an unbiased manner in 201 patients with prevalent VTE as well as 43 healthy controls. We used a bioinformatics approach to develop a unique signature for VTE by identifying differentially expressed genes, developing cell-type modules, and ascertaining pathways driving differentially expressed transcripts. We performed additional analyses on subgroups of patients with idiopathic VTE, patients with incident VTE, and VTE patients matched to healthy controls by age and sex. We went on to use machine learning methods to learn models that best differentiate VTE patients from healthy controls and validated it on a left out test set within our VTE population. Genes specific to neutrophils, erythrocytes, and platelets, in that order, were most significantly upregulated in patients with VTE compared to healthy controls. Genes related to T-cells were downregulated. Pathway analysis revealed upregulated neutrophil activation and degranulation, erythrocyte differentiation and homeostasis, and platelet degranulation. A gene signature of 217 transcripts was outstanding at differentiating patients with VTE versus healthy controls (AUC 0.94). Following adjustment for age, sex, and race/ethnicity our genetic signature remained significantly robust at differentiating patients with VTE versus controls (AUC 0.83). Our expression signature remained stable across patients with idiopathic VTE (AUC 0.93), and in patients who went on to develop future VTE events (AUC 0.95). In summary, we have demonstrated a whole blood transcriptional signature for prevalent and incident VTE. Genes related to neutrophils, erythrocytes, and platelets are upregulated in patients with VTE and genes related to T-cells were downregulated. These findings suggest an active role of cell types once thought to be passively entrapped within thrombus and provide new areas of study to establish the pathophysiology of VTE

Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.

Each year, more than 300 million patients worldwide undergo non-cardiac surgery. Perioperative myocardial infarction (MI) is a common cardiovascular complication of surgery; thus, we sought to determine coronary artery anatomy in patients referred for coronary angiography for the evaluation of perioperative MI after non-cardiac surgery.