Studies show that chest CT scanning increases the detection rates for ILL and pulmonary metastases. The clinical benefit of the increased detection rates is not clear. There is a paucity of data assessing the optimal chest staging strategy for patients presenting with CRC.
At the 3-year colonoscopic follow up, folate supplementation had no effect on adenoma recurrence overall. While colonic surveillance beyond 3 years revealed an increased risk of colorectal adenoma, especially advanced adenoma, among those participants randomized to the folate group. This meta-analysis challenges the results from epidemiological studies that folate status is inversely related to the risk of developing colorectal cancer.
The adenosine analogue remdesivir has emerged as a frontline antiviral treatment for SARS-CoV-2, with preliminary evidence that it reduces the duration and severity of illness1. Prior clinical studies have identified adverse events1,2, and remdesivir has been shown to inhibit mitochondrial RNA polymerase in biochemical experiments7, yet little is known about the specific genetic pathways involved in cellular remdesivir metabolism and cytotoxicity. Through genome-wide CRISPR-Cas9 screening and RNA sequencing, we show that remdesivir treatment leads to a repression of mitochondrial respiratory activity, and we identify five genes whose loss significantly reduces remdesivir cytotoxicity. In particular, we show that loss of the mitochondrial nucleoside transporter SLC29A3 mitigates remdesivir toxicity without a commensurate decrease in SARS-CoV-2 antiviral potency and that the mitochondrial adenylate kinase AK2 is a remdesivir kinase required for remdesivir efficacy and toxicity. This work elucidates the cellular mechanisms of remdesivir metabolism and provides a candidate gene target to reduce remdesivir cytotoxicity.
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