Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.
Purpose
The coronavirus disease 2019 (COVID-19) pandemic has led to substantial disruptions in healthcare staffing and operations. Stay-at-home (SAH) orders and limitations in social gathering implemented in spring 2020 were followed by initial decreases in healthcare and imaging utilization. This study aims to evaluate the impact of subsequent easing of SAH on trauma volumes, demand for, and turnaround times for trauma computed tomography (CT) exams, hypothesizing that after initial decreases, trauma volumes have increased as COVID safety measures have been reduced.
Methods
Patient characteristics, CT imaging volumes, and turnaround time were analyzed for all adult activated emergency department trauma patients requiring CT imaging at a single Level-I trauma center (1/2018–2/2022) located in the sixth most populous county in the USA. Based on COVID safety measures in place in the state of California, three time periods were compared: baseline (PRE, 1/1/2018–3/19/2020), COVID safety measures (COVID, 3/20/2020–1/25/2021), and POST (1/26/2021–2/28/2022).
Results
There were 16,984 trauma patients across the study (PRE = 8289, COVID = 3139, POST = 5556). The average daily trauma patient volumes increased significantly in the POST period compared to the PRE and COVID periods (13.9 vs. 10.3 vs. 10.1, p < 0.001), with increases in both blunt (p < 0.001) and penetrating (p = 0.002) trauma. The average daily number of trauma CT examinations performed increased significantly in the POST period compared to the PRE and COVID periods (56.7 vs. 48.3 vs. 47.6, p < 0.001), with significant increases in average turnaround time (47 min vs. 31 and 37, p < 0.001).
Conclusion
After initial decreases in trauma radiology volumes following stay-at-home orders, subsequent easing of safety measures has coincided with increases in trauma imaging volumes above pre-pandemic levels and longer exam turnaround times.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.