The prognostic value of positron emission tomography in the evaluation of suspected cardiac sarcoidosis.

OBJECTIVES: To assess the prognostic value of positron emission tomography (PET) imaging in patients undergoing evaluation for known or suspected cardiac sarcoidosis (CS) while not on active immunotherapy. BACKGROUND: Previous studies have attempted to identify the value of PET imaging to aid in risk stratification of patients with CS, however, most cohorts have included patients currently on immunosuppression, which may confound scan results by suppressing positive findings. METHODS: We retrospectively analyzed 197 patients not on immunosuppression who underwent 18F-fluorodeoxyglucose (FDG) PET scans for evaluation of known or suspected CS. The primary endpoint of the study was time to ventricular arrhythmia (VT/VF), or death. Candidate predictors were identified by univariable Cox proportional hazards regression. Independent predictors were identified by performing multivariable Cox regression with stepwise forward selection. RESULTS: Median follow-up time was 531 [IQR 309, 748] days. 41 patients met the primary endpoint. After stepwise forward selection, left ventricular ejection fraction (LVEF) (HR 0.98, 95% CI 0.96-0.99, P = 0.02), history of VT/VF (HR 4.19, 95% CI 2.15-8.17, P < 0.001), and summed rest score (SRS) (HR 1.06, 95% CI 1.02-1.12, P = 0.01) were predictive of the primary endpoint. Quantitative and qualitative measures of FDG uptake on PET were not predictive of clinical events. CONCLUSIONS: Among untreated patients who underwent PET scans to evaluate known or suspected CS, LVEF, history of VT/VF, and SRS were associated with adverse clinical outcomes.

Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic CD8+ DCs in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43-containing gap junctions between monocytes and DCs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8+ DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.

Primary and Secondary Vascular Access Site Complications Associated With Percutaneous Coronary Intervention: Insights From the BMC2 Registry.

OBJECTIVES: This study sought to describe the association between trends in primary and secondary vascular access sites and vascular access site complications (VASCs) among patients who underwent percutaneous coronary intervention (PCI) in Michigan. BACKGROUND: The frequency of transradial PCI has increased. As a result, there is concern that operators may lose femoral-access proficiency resulting in a paradoxical increase in PCI complications. Anecdotally, an increase in secondary access use during PCI has also been observed. METHODS: Data from the BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) registry was queried to evaluate the use of transradial and transfemoral PCI and their associated VASCs. RESULTS: From 2013 to 2017, transradial PCI increased from 25.9% to 45.2% and the overall use of secondary vascular access increased from 4.9% to 8.7% with minimal change in overall VASCs (1.2% to 1.4%). The use of secondary vascular access was associated with increased VASCs (odds ratio [OR]: 5.82; 95% confidence interval [CI]: 5.26 to 6.43). Although, patients treated by operators in the highest tertile of radial use were more likely to experience femoral VASCs (adjusted OR: 1.51; 95% CI: 1.08 to 2.13), treatment by these operators was associated with an overall reduction in all VASCs (adjusted OR: 0.62; 95% CI: 0.46 to 0.83). CONCLUSIONS: Despite increased use of transradial PCI, there has been no significant decrease in VASCs. This is in part attributable to an increased incidence of femoral VASCs and increasing use of secondary vascular access. An overall reduction in VASCs was observed in the highest radial use operators. Further strategies are needed to reduce VASCs in the transradial era.

Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial.

BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. METHODS: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group). RESULTS: At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted <5 days post-PCI, and 30% stopped and restarted >5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62). CONCLUSIONS: PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI.

A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues.

Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions.