Emergency Department Doppler Assessment of a Central Retinal Artery Occlusion: Case Report.

Introduction: Vision loss is a symptom found frequently in patients presenting to the emergency department (ED). Central retinal artery occlusion (CRAO) is an uncommon yet time-sensitive and critical cause of painless vision loss in which delayed diagnosis can lead to significant morbidity. Emergency medicine literature documents the ability to diagnose a CRAO using ultrasound by identifying the hyperechoic thrombus-coined the retrobulbar spot sign. Case Report: We present the case of a patient presenting with painless monocular vision loss for which CRAO was diagnosed in the ED using point-of-care ultrasound enhanced by the utilization of serial Doppler examinations as well as calculation of the central retinal artery resistive index. Conclusion: Despite the pre-existing literature on point-of-care ultrasound investigation of central retinal artery occlusion, there are no emergency medicine case reports describing serial examination of the central retinal artery by spectral Doppler or calculation of arterial resistive index to improve this evaluation and monitor progression of the pathology.

Examining D-dimer and Empiric Anti-coagulation in COVID-19-Related Thrombosis.

Objective Thrombosis is thought to occur frequently in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to elucidate the relationship between macro/microvascular thrombosis, D-dimer levels, and empiric anticoagulation in coronavirus disease 2019 (COVID-19). Methods This was an exploratory prospective, single-site, observational study. Adult emergency department patients with COVID-19 requiring hospitalization received a point-of-care lower extremity venous duplex ultrasound. The primary endpoint was thromboembolism and associated D-dimer level. Secondary endpoints included rates of micro and macro thrombotic complications as well as empiric anticoagulant use. Results Between January 13th and April 12th 2021, 52 patients were enrolled. Median D-dimer at presentation was 650 ng/mL (range 250-10,000 ng/mL) among patients with negative duplex studies. During hospitalization, 18 patients underwent 20 additional studies assessing for venous thromboembolism (VTE). These studies yielded one deep vein thrombosis (DVT) diagnosis. Among patients with negative studies median D-dimer was 1,246 ng/mL (range 329-10,000 ng/mL). Two patients experienced microvascular complications. Seven patients were started on empiric full dose anticoagulation. Conclusion While VTE remains a major concern amongst patients with COVID-19, the normal D-dimer cut off of >500 ng/mL likely should not be used to initiate further VTE workup. Additionally, moderately elevated D-dimer did not correlate strongly with microvascular complications and may not be relevant in the decision to initiate empiric anticoagulation.

An OX40/OX40L interaction directs successful immunity to hepatitis B virus.

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB.

Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1.

Post-translational modifications of histone play important roles in gene transcription. Aberrant methylation of histone lysine sidechains have been often found in cancer. Lysine specific demethylase 1 (LSD1), which can demethylate histone H3 lysine 4 (H3K4) and other proteins, has recently been found to be a drug target for acute myeloid leukemia. To understand structure activity/selectivity relationships of LSD1 inhibitors, several series of cyclopropylamine and related compounds were synthesized and tested for their activities against LSD1 and related monoamine oxidase (MAO) A and B. Several cyclopropylamine containing compounds were found to be highly potent and selective inhibitors of LSD1. A novel series cyclopropylimine compounds also exhibited strong inhibitory activity against LSD1. Structure activity relationships (SAR) of these compounds are discussed. Docking studies were performed to provide possible binding models of a representative compound in LSD1 and MAO-A. Moreover, these modeling studies can rationalize the observed SARs and selectivity.