Incremental prognostic value of spect over CCTA.

BACKGROUND: Coronary computed tomographic angiography (CCTA) and Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) provide comprehensive anatomic and functional assessment of the coronary arteries useful in the diagnosis and prognosis of patients with coronary artery disease (CAD). We aimed to assess the incremental prognostic role of SPECT physiologic assessment to CCTA in patients with suspected CAD. METHODS: Consecutive patients with suspected CAD undergoing clinically indicated CCTA within 180 days of undergoing SPECT were included. Patients were followed for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention or coronary artery bypass grafting 90-days after imaging test.) RESULTS: The cohort consisted of 956 patients (mean age 61.1 ± 14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive stenosis was found in 14% of patients, while scar (fixed perfusion defect), ischemia and left ventricular ejection fraction <40% were found in 17, 14 and 9% of patients, respectively. In nested multivariable cox regression models, perfusion and left ventricular function when added to a model with CCTA obstructive stenosis significantly improved model risk prediction (Harrell's C = 0.73, p = 0.037) and risk reclassification on a continuous scale (P < 0.001). CONCLUSION: We have shown that a combined assessment of perfusion burden and left ventricular function added incremental value over and above a CCTA based anatomic assessment in patients with suspected CAD.

Assessment of the immune landscapes of advanced ovarian cancer in an optimized in vivo model.

BACKGROUND: Ovarian cancer (OC) is typically diagnosed late, associated with high rates of metastasis and the onset of ascites during late stage disease. Understanding the tumor microenvironment and how it impacts the efficacy of current treatments, including immunotherapies, needs effective in vivo models that are fully characterized. In particular, understanding the role of immune cells within the tumor and ascitic fluid could provide important insights into why OC fails to respond to immunotherapies. In this work, we comprehensively described the immune cell infiltrates in tumor nodules and the ascitic fluid within an optimized preclinical model of advanced ovarian cancer. METHODS: Green Fluorescent Protein (GFP)-ID8 OC cells were injected intraperitoneally into C57BL/6 mice and the development of advanced stage OC monitored. Nine weeks after tumor injection, mice were sacrificed and tumor nodules analyzed to identify specific immune infiltrates by immunohistochemistry. Ascites, developed in tumor bearing mice over a 10-week period, was characterized by mass cytometry (CyTOF) to qualitatively and quantitatively assess the distribution of the immune cell subsets, and their relationship to ascites from ovarian cancer patients. RESULTS: Tumor nodules in the peritoneal cavity proved to be enriched in T cells, antigen presenting cells and macrophages, demonstrating an active immune environment and cell-mediated immunity. Assessment of the immune landscape in the ascites showed the predominance of CD8+ , CD4+ , B- , and memory T cells, among others, and the coexistance of different immune cell types within the same tumor microenvironment. CONCLUSIONS: We performed, for the first time, a multiparametric analysis of the ascitic fluid and specifically identify immune cell populations in the peritoneal cavity of mice with advanced OC. Data obtained highlights the impact of CytOF as a diagnostic tool for this malignancy, with the opportunity to concomitantly identify novel targets, and define personalized therapeutic options.