New colorectal cancer (CRC) screening guidelines from the United States Multi-Society Task Force (MSTF) on Colorectal Cancer (CRC) suggest screening in average-risk individuals ages 45–49 (Am J Gastroenterol 2021; doi: 10.14309/ajg.0000000000001548).

Although no literature demonstrates that CRC screening in average risk individuals younger than 50 improves health outcomes such as CRC incidence or mortality, the task force made the recommendation based on research showing increased CRC incidence and mortality in individuals under ages 50. Emerging data also indicate the prevalence of advanced colorectal neoplasia in individuals ages 45–49 approaches rates for those ages 50–59. Modeling studies show that the benefits of screening outweigh potential harms and costs, the task force said.

The task force recommendations were last issued in 2017. The 2021 update contains several recommendations that remain unchanged from 2017 guidelines. For example, the task force strongly recommends CRC screening in all individuals ages 50–75 who have not already initiated screening. For individuals ages 76–85, the decision to start or continue screening should be individualized and based on prior screening history, comorbidity, life expectancy, CRC risk, and personal preference. Additionally, screening is not recommended after age 85, according to new guidelines.

The task force says its updated guidance from the MSTF is aligned with multiple other professional societies, including the United States Preventative Services Task Force, the National Comprehensive Cancer Network, and the American Cancer Society. Currently, insufficient evidence precludes recommending a screening method or customized screening intervals.

CRISPR SARS-CoV-2 Assay Could Help Meet Global Demand

A high-throughput CRISPR-Cas13 SARS-CoV-2 test can identify the SARS-CoV-2 virus with high concordance to RT-qPCR, according to a recent Clinical Chemistry paper (2021; doi: 10.1093/clinchem/hvab238).

As the COVID-19 pandemic continues, having a high-throughput, flexible molecular method could help high-complexity laboratories increase their testing capacities quickly using simple equipment, according to the authors. This situation also would provide some relief to pressure on lab supply chains.

The CRISPR test relies on specific high-sensitivity enzymatic reporter unlocking (SHERLOCK) for qualitative detection of SARS-CoV-2 RNA. SHERLOCK is a CRISPR-based diagnostic that enables DNA or RNA detection with single-nucleotide specificity using CAS13a from L. wadei combined with isothermal amplification. The test may be performed directly on swabs or saliva samples without nucleic acid extraction and provides results in an hour.

The Food and Drug Administration earlier this year granted the first emergency use authorization for a CRISPR diagnostic test to the original SHERLOCK CRISPR SARS-Cov-2 kit. It detects the virus’s nucleic acids in upper respiratory tissue. A recent report says this assay was 100% concordant to RT-PCR in detecting SARS-CoV-2 in clinical nasopharyngeal samples.

The new assay improves on the first test by allowing a simpler workflow. It enables testing up to 5,000 patient samples based on a single operator and instrument, according to the paper. For example, the new test combines two independent SARS-CoV-2 targets in a single reaction to ease sample preparation and uses a 384-well format with minimal liquid handling steps to increase throughput and better work with automated processes. The new test also uses an extraction method involving a simple heat and proteinase K treatment, which is enough to allow direct sample addition to a SHERLOCK reaction while maintaining high sensitivity and specificity.

The researchers evaluated their assay using 55 negative and 50 positive remnant SARS-CoV-2 specimens. When combined with magnetic bead-based extraction on 60 of these samples, the new assay was 100% concordant with the Centers for Disease Control and Prevention (CDC) RT-qPCR assay. With the direct sample addition, the new assay was also 100% concordant with the CDC RT-qPCR direct method in 45 samples. Using direct saliva samples, the negative and positive agreements were 100% and 88%, respectively, compared with results from a collaborating clinical laboratory.

Better Lab Stewardship of Anemia Tests May Be Needed

Overuse of laboratory screening tests for iron-deficiency anemia (IDA) and misinterpretation of iron studies in part lead to delayed diagnosis of gastrointestinal (GI) tract cancers, according to a recent paper. The authors also blamed underuse of bidirectional endoscopy for evaluation of new-onset IDA (JAMA Netw Open 2021; doi:10.1001/jamanetworkopen.2021.27827).

IDA is a classic early sign of GI tract malignant neoplasm, the study says. Up to 10% of patients with IDA may have undiagnosed GI tract cancer, so prompt evaluation is important. However, retrospective studies report common delays in diagnostic evaluation of IDA, which can lead to delayed colorectal cancer diagnosis. Meanwhile, colorectal cancer cases are rising in patients younger than the recommended age for start of screening. At least 30 different guidelines from 10 specialty societies make different recommendations for identification and evaluation of IDA.

To understand how primary care physicians handle IDA testing and evaluation, the researchers administered a survey consisting of questions about vignettes describing related clinical scenarios. In a survey of 325 primary care physicians, 76.9% of respondents said they screened at least some patients for anemia. Interpretation of iron studies was least accurate in a scenario of a borderline low ferritin level (40 ng/mL) with low transferrin saturation (2%). Just over a quarter of respondents—26.5%—incorrectly responded that this scenario did not indicate IDA, and 73.5% correctly identified this scenario as IDA. Of 312 participants, 54.5% recommended bidirectional endoscopy (upper endoscopy and colonoscopy) for new IDA for women age 65 years. Of 305 respondents, 168 (55.1%) recommended bidirectional endoscopy for men age 65 years.

The researchers say these findings suggest a need for design and use of tools to improve diagnosis of IDA and reduce risk of diagnostic errors.