Impact of COVID-19 Pandemic on Sex and Racial Disparities in Chest Pain Presentation and Management Through the Emergency Department.

Background: Sex and racial disparities in the presentation and management of chest pain persist, however, the impact of coronavirus disease 2019 (COVID-19) on these disparities have not been studied. We sought to determine whether the COVID-19 pandemic contributed to pre-existing sex and racial disparities in the presentation, management, and outcomes of patients presenting to the emergency department (ED) with chest pain. Methods: We conducted an observational cohort study with retrospective data collection of patients between January 1, 2016, and May 1, 2022. This was a single study conducted at a quaternary academic medical center of all patients who presented to the ED with a complaint of chest pain or chest pain equivalent symptoms. Patient were further segregated into different groups based on sex (male, female), race, ethnicity (Asian, Black, Hispanic, White, and other), and age (18 - 40, 41 - 65, > 65). We compared diagnostic evaluations, treatment decisions, and outcomes during prespecified time points before, during, and after the COVID-19 pandemic. Results: This study included 95,764 chest pain encounters. Total chest pain presentations to the ED fell about 38% during the early pandemic months. Females presented significantly less than males during initial COVID-19 (48% vs. 52%, P < 0.001) and Asian females were least likely to present. There was an increase in the total number of troponins and echocardiograms ordered during peak COVID-19 across both sexes, but females were still less likely to have these tests ordered across all timepoints. The number of coronary angiograms did not increase during peak COVID-19, and females were less likely to undergo coronary angiogram during all timepoints. Finally, females with chest pain were less likely to be diagnosed with acute myocardial infarction (AMI) during all timepoints, while in-hospital deaths were similar between males and females during all timepoints. Conclusions: During COVID-19, females, especially Asian females, were less likely to present to the ED for chest pain. Non-White patients were less likely to present to the ED compared to White patients prior to and during the pandemic. Disparities in management and outcomes of chest pain encounters remained similar to pre-COVID-19, with females receiving less cardiac workup and AMI diagnoses than males, but in-hospital mortality remaining similar between groups and timepoints.

HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Discovery and characterization of circulating tumor cell clusters in neuroendocrine tumor patients using nanosubstrate-embedded microchips.

Circulating tumor cell (CTC) clusters are present in cancer patients with severe metastasis, resulting in poor clinical outcomes. However, CTC clusters have not been studied as extensively as single CTCs, and the clinical utility of CTC clusters remains largely unknown. In this study, we aim sought to explore the feasibility of NanoVelcro Chips to simultaneously detect both single CTCs and CTC clusters with negligible perturbation to their intrinsic properties in neuroendocrine tumors (NETs). We discovered frequent CTC clusters in patients with advanced NETs and examined their potential roles, together with single NET CTCs, as novel biomarkers of patient response following peptide receptor radionuclide therapy (PRRT). We observed dynamic changes in both total NET CTCs and NET CTC cluster counts in NET patients undergoing PRRT which correlated with clinical outcome. These preliminary findings suggest that CTC clusters, along with single CTCs, offer a potential non-invasive option to monitor the treatment response in NET patients undergoing PRRT.

The Role of Extracellular Vesicles in Disease Progression and Detection of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer-related death worldwide. Despite the improvements in surveillance and treatment, the prognosis of HCC remains poor. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles circulating in the bloodstream and mediating intercellular communication. Emerging studies have shown that EVs play a crucial role in regulating the proliferation, immune escape, and metastasis of HCC. In addition, because EVs are present in the circulation at relatively early stages of disease, they are getting attention as an attractive biomarker for HCC detection. Over the past decade, dedicated efforts have been made to isolate EVs more efficiently and make them useful tools in different clinical settings. In this review article, we provide an overview of the EVs isolation methods and highlight the role of EVs as mediators in the pathogenesis and progression of HCC. Lastly, we summarize the potential applications of EVs in early-stage HCC detection.