Rivaroxaban is a novel anticoagulant approved for use in patients with atrial fibrillation for stroke prevention. It is a factor Xa inhibitor, and its activity cannot be monitored with use of the international normalized ratio. A 5.6% chance of major bleeding is associated with rivaroxaban use, including intracranial and gastrointestinal bleeds. We report the first case, to our knowledge, of isolated hemopericardium related to rivaroxaban use, which could potentially lead to death from cardiac tamponade. A 76-year-old man who was receiving rivaroxaban for atrial fibrillation presented to the emergency department with pleuritic chest pain and was found to have a hemopericardium. No signs of tamponade were evident, and his bleed remained stable after discontinuing rivaroxaban. The patient had also been taking saw palmetto, which may have contributed to the bleed by increasing rivaroxaban activity. A work-up for other causes of hemopericardium, including pacemaker lead misplacement and autoimmune disease-related pericarditis, was negative. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hemopericardium and rivaroxaban use. This case highlights the potential for bleeding complications associated with novel anticoagulants. Herbal products and various drugs may increase rivaroxaban levels by inhibiting P-glycoprotein and cytochrome P450 3A4 activity. Clinicians should be aware of these potential interactions with rivaroxaban and perform a review of not only the patient's drug therapy but also any herbal and food products that could alter the levels of anticoagulants. The lack of an antidote and the inability to dialyze rivaroxaban is a significant concern in situations of life-threatening bleeds. A laboratory test for monitoring rivaroxaban levels may be required for its safe use.

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Understanding the tumor microenvironment (TME) requires more than just a catalog of cell types and gene programs. It is critical to see the spatial organization of the cells are and where they form multicellular interaction networks. Here we present a single-cell spatially resolved transcriptomic analysis of human mismatch repair deficient (MMRd) and proficient (MMRp) colorectal cancer (CRC) specimens. High tumor mutational burden MMRd tumors are known to have an immune response characterized by higher cytolytic T cell infiltrates compared to MMRp tumors, making them an ideal system for spatial single-cell profiling and understanding how the immune-driven programs differ between these tumors. MERFISH is a massively multiplexed single molecule imaging technology which can simultaneously capture and measure the quantity and distribution of hundreds to thousands of RNA species within single cells across a tissue1. We designed a MERFISH library of over 450 genes including genes important to proliferation, apoptosis, immune signaling, immune cell type pathways and other critical pathways in CRC. Patient samples, obtained commercially or through MGH, were hybridized with the designed MERFISH library and stained with a cell boundary marker to delineate cells across the tissue. We performed unsupervised clustering to identify cell types and we calculated spatial statistics to characterize how the cell type distribution varied between MMRd and MMRp tumors. We identified the cellular composition of each tumor, including immune and stromal cells, and the spatial distribution of these cell types. We were able to readily identify all cell types and states previously discovered by single-cell RNA sequencing2 in intact patient specimens, thus providing an accurate map of the cellular composition and spatial organization of these cells in the tumor microenvironment. We transformed these cell types into neighborhoods and discovered a highly organized spatial distribution of most cell types throughout the tumor. While spatial organization was observed in both MMRp and MMRd CRC we saw a significant shift in spatial organization between these tumor classifications notably in the immune population. Further, previously predicted multicellular interaction networks2 appeared as spatially organized structures in the tissue and were distinct in MMRd versus MMRp tumor specimens. Our data provide a richness of concrete hypotheses about which cells are working together, how these cells function cooperatively, and where these cells are located which will be critical in advancing therapy in these immunologically distinct types of colorectal cancer. These cancer maps are critical to truly understand the biology of CRC as well as identify avenues for the development of future therapies for CRC patients. Citation Format: Colles Price, Jonathan H. Chen, Karin Pelka, Sherry Chao, Michael Therrien, Timothy Wiggin, Nicolas Fernandez, Jiang He, George Emanuel, Genevieve Boland, Nir Hacohen. A single-cell spatially resolved map of colorectal cancer identifies novel spatial relationships between cancer cells and the microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2030.

Transthoracic echocardiography is generally accepted as the procedure of choice for diagnosing Ebstein's anomaly; however, an optimal evaluation is not always possible due to technical limitations. We have reported the utility of transesophageal echocardiography and Doppler color flow mapping in this condition, particularly for demonstrating structures and flow patterns in the atria and right ventricle. We conclude that in the evaluation of Ebstein$ anomaly, these two echocardiographic techniques are complementary and together can provide an excellent anatomical and functional assessment. (ECHOCARDIOGRAPHY, Volume 8, May 1991)