The Super Bowl is coming up this weekend, and we’re excited - for what might be the funniest TV ads of the year! (Though we frankly doubt this one will ever be topped.) Here’s a buffet of diagnostic tidbits to tide you over until the big event.
(Oh, and we hear something else is happening that day, too - Taylor Swift is going to a big arena to see her boyfriend play some game or other. Mara’s team isn’t playing, so whatever.)
Biomarkers
Sweat is an under-appreciated bodily fluid in the diagnostics field. At the 2024 Crohn’s & Colitis Congress, researchers presented the results of a small study that used biomarkers of inflammation (CRP, IL-6, and calprotectin) in sweat to detect inflammatory bowel disease flares. The sweat was captured into a watch-sized device which then performed the biochemical analysis.
“Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options,” researchers write in a recent Cell Reports Medicine paper. Excitingly, they found that an enzyme with the intimidating name of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is not only a biomarker for these diseases (it’s elevated in plasma of neuroendocrine carcinoma patients), but that it can be successfully targeted with an inhibitor - in mouse models, at least.
Vending Machines for your Rapid Test
COVID taught us that the timeliness of rapid testing is key for behavior change and treatment uptake. The Washington Post covered a UK vending machine program that offers free STI tests in exchange for completing a simple survey - details of the program can be found in this BMJ paper. The UK research project offered self-collection kits for mail-in analysis (postage free), with results coming by text message in an average of 5-10 days. Uptake was strong, especially among younger age groups (48% of users were 16-25, and a further 29% were 26-35 years old). These cohorts are more sexually active and less likely to visit a doctors office or clinic, but they were more comfortable with a confidential / low embarrassment / anonymous process provided in social settings where sexual encounters begin. Those who completed a survey cited convenience and privacy as most appreciated. Test purchasing through vending machines is not unique. For example, there are similar vending machines, with COVID tests, in the Manila International Airport in the Philippines.
Commentary: It would be reasonable to assume that dispensing true self-tests (not just self-collection kits) would increase uptake even further, even with a reasonable charge (and without an extensive survey). Public health is often thought of as a centralized activity that generates data for changes in policy, but the foundation of an effective program is getting more of the public to routinely incorporate testing into their everyday behavior.
Regulation and Guidelines
The FDA is widely expected to finalize a rule to regulate laboratory-developed tests (LDTs) this spring. In a move seen as part of the groundwork for this change, the FDA announced plans to reclassify most high-risk IVDs (Class III devices) to moderate-risk IVDs (Class II devices). The significance? Most Class II tests only require a 510(k) submission process; Class III tests require the more stringent PMA (Pre Market Approval) process. The agency said in a statement that they believe this shift will encourage more test manufacturers to develop more tests.
Since the 1940s, per- and polyfluoroalkyl substances (PFAS) have been used in everything from food packaging to firefighting foam. They’re extremely stable compounds that don’t break down in the environment or your body, earning them the nickname “forever chemicals.” According to new CDC guidelines issued last month, if a patient has a history of potential exposure to PFAS, the levels of these compounds in their blood should be tested.
Commentary: Since we basically all have exposure (have you eaten food from grease-resistant packaging, or do you have stain-resistant carpets? Yeah, me too) and there isn’t any way to remove these compounds from the body, it’s not clear why testing for PFAS levels will help. We will learn more about relevance and calibration if many people choose to test.
The CDC published new recommendations for syphilis today - the first to address laboratory testing for the disease. Labs are urged to test both for the presence of the microbe that causes syphilis (an indication of active infection) as well as for antibodies to that microbe (present in both past and current infection).
Imaging
Clinicians currently estimate the severity of ulcerative colitis (a form of inflammatory bowel disease) using a scoring system. Research published in Gastrointestinal Endoscopy showed that the more severe colitis is, the lower the oxygen saturation is in the mucosal layer of the colon - allowing oxygen saturation measured on endoscopy to serve as an objective way to measure the severity of the disease.
The FDA has approved a software package that analyzes MRI scans which look for neuromelanin. This dark pigment is present and tends to build up in areas of the human brain that degenerate in Parkinson’s disease. The system gives clinicians a standardized and automated way to interpret neuromelanin-sensitive MRI.
A two-stage screening protocol increased the likelihood of diagnosing ovarian cancer at an early stage (rather than a late stage). The long-term study looked at post-menopausal women at no increased risk of ovarian cancer. Those who had a high or rising serum level of cancer antigen 125 (CA 125) were referred for transvaginal ultrasound. The screening system reduced late-stage (III - IV) diagnosis by 30% compared to historical levels of diagnosis in the US.
Genetics and Epigenetics
Two recent studies highlighted the importance of DNA methylation in cancer diagnostics, both on the horizon and in the future. (DNA methylation changes the expression patterns of genes.) One described an assay that uses DNA methylation patterns to identify castration-resistant neuroendocrine prostate cancer, a subtype that historically has been difficult to diagnose. The other used a mouse model to show that whether cancer cells metastasize doesn’t depend on tumor genetics - it depends on how methylated the tumor DNA is. Cells whose DNA was more methylated metastasized; those with less-methylated DNA didn’t, a finding that has relevance for tumor staging.
Gestational diabetes mellitus (GDM) currently can’t be diagnosed until late in the course of pregnancy (after 24 weeks), even though it starts causing problems earlier. An AI-based method described recently in Briefings in Bioinformatics was able to predict GDM as early as 12 weeks, using cell-free DNA found in the pregnant person’s blood plasma. While the paper claimed the technique had roughly 93% accuracy, the authors acknowledged that it needs further testing with larger, unrelated datasets.
A team at the University of Chicago has developed a statistical model that improves scientists’ ability to figure out which sets of genetic variants actually cause diseases. The model combines genome-wide association studies (GWAS) with information about how genes are expressed. Crucially, it is able to account for multiple genes and variants rather than looking at a single gene at a time - a technique that decreases the false positive rate. The software is available for download from the researchers’ website.
Data Mining
A team from Beth Israel Deaconess Cancer Center used AI to analyze electronic health records, looking for patterns that predicted a diagnosis of pancreatic cancer. The model they developed was able to find 3.5x more cases as compared to current screening protocols, and had similar accuracy in diverse populations of patients. We covered an AI-enhanced CT technique for pancreatic cancer detection in our January 18 issue.
COVID EUA Update
The FDA issued no new COVID 510(k) premarket notifications, no new EUAs, six amendments to existing EUAs, and six new revocations in January.
510(k) Premarket Notifications: (0)
New EUAs: (0)
Amendments to Existing EUAs (6):
Molecular: 3
COVID Antigen: 2
Flu / RSV Panels: 1
Revocations: (6) PerkinElmer SARS-CoV-2 RT-qPCR Reagent Kit | VIDAS SARS-CoV-2 IgG | VIDAS SARS-CoV-2 IgM | TangenDx SARS-CoV-2 Molecular Test | Bio-Rad Reliance SARS-CoV-2 RT-PCR Assay Kit | TaqPath COVID-19 Pooling Kit